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A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies

The purpose of this Phase 1 study is to determine the safety, tolerability, maximum tolerated dose, and (preliminary) effectiveness of oral DCC-2618 in patients with advanced malignancies. The study will also determine the pharmacokinetic and pharmacodynamics profile of oral DCC-2618. The study will consist of an Escalation Phase in patients with advanced malignancies (to test safety and to determine the maximum tolerated dose of the study drug) followed by an Expansion Phase in select tumors (to further test the safety and tolerability and to obtain preliminary evidence of efficacy of the study drug). At Stanford we will be taking part in the expansion phase, for patients with GIST.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Deciphera Pharmaceuticals LLC

Intervention(s):

  • Drug: DCC-2618

Phase:

Phase 1

Eligibility


Inclusion Criteria (Escalation and Expansion Phases)

Patients must meet the following criteria to be eligible to enroll in the study:

   1. Patients must have histologically confirmed solid tumors or hematologic malignancies.
   Eligible patients include the following:

   a) GIST patients must have a KIT and PDGFRA mutation and must have progressed on or
   had an intolerability to at least 1 line of systemic anticancer therapy: i. Patients
   with a pre-existing resistance mutation to an approved line of therapy are eligible.
   For example, imatinib resistant mutations including KIT Exon 17 and PDGFRA D842V.

   b) SM patients must have a confirmed diagnosis (confirmed by a central independent
   pathologist) of advanced SM according to 2016 World Health Organization (WHO) criteria
   for SM and must have documented KIT mutant disease. SM patients must also have a
   normal karyotype.

   Advanced SM includes: ASM, SM-AHN, wherein the AHN does not require immediate
   alternative therapy, such as acute myeloid leukemia. AHNs that are eligible include:
   low grade myelodysplastic syndrome (MDS) with a high SM burden who require treatment
   for SM only, myeloproliferative neoplasms (MPNs), MDS/MPN, and HES/CEL], and MCL i.
   Patients with advanced SM must present with at least 1 eligible C-Finding (organ
   damage) as outlined in Table 3 of the 2013 International Working
   Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European
   Competence Network on Mastocytosis (ECNM) consensus response criteria (Appendix 10.5);
   please see below for MCL exception) (#iii).

   ii. Patients with imatinib-sensitive KIT mutations must have progressed on or were
   intolerant to a tryosine kinase inhibitor.

   iii. Patients with histopathologically-confirmed MCL without a C-finding are eligible.

   iv. Patients with symptomatic SSM are eligible. By definition, SSM patients must have
   at least 2 B-findings, and clinically significant symptom burden (eg, flushing,
   diarrhea, etc.) despite maximal treatment with approved agents to treat mediator
   symptoms, such as antihistamines and cromolyn sodium. Patients must have a normal
   karyotype.

   v. Patients with hematologic malignancies featuring clonal expansion of eosinophils
   driven by genomic alterations of KIT or PDGFR (eg, HES or CEL) must have a diagnosis
   confirmed by a central independent pathologist and are eligible if they have
   progressed on or are intolerant of imatinib therapy. Patients with de novo imatinib
   resistant mutations, such as but not limited to KIT D816V or PDGFRA D842V, are
   eligible without prior imatinib therapy.

   c) Malignant glioma patients with genomic alterations potentially conferring
   sensitivity to DCC-2618 including, but not limited to, amplification and/or mutations
   of PDGFRA and/or KIT.

   i. Patients must not require use of enzyme-inducing antiepileptic drugs. ii. Patients
   that require steroids must be on a stable dose for 2 weeks prior to the first dose of
   study drug.

   d) Other solid tumor patients that have alterations in genes encoding kinases that are
   targets of DCC-2618. This includes KIT, PDGFR (A or B), TIE2, CSF1R, and VEGFR2.
   Patients must have received approved treatments known to provide clinical benefit
   prior to study entry.

   e) If signs or symptoms suggest CNS metastases, a brain MRI must be performed to
   confirm absence of CNS disease within 1 week prior to receiving study drug.

   2. Patients with known CNS metastases may participate provided that:

      1. they are stable (ie, without evidence of progression by magnetic resonance
      imaging [MRI]) for at least 4 weeks prior to the first dose study drug (patients
      with active disease may be eligible following discussion between the Investigator
      and the Sponsor),

      2. all neurologic symptoms have been stable for 2 weeks prior to the first dose of
      study drug,

      3. patients must not require use of enzyme-inducing antiepileptic drugs,

      4. patients that require steroids must be on a stable dose for 2 weeks prior to the
      first dose of study drug.

   3. Patients with solid tumors (with the exception of glial tumors and tumors that are
   anatomically inaccessible) must have an archival tumor biopsy sample as long as no
   anticancer therapy was administered since the sample was collected; otherwise, a
   current biopsy is required. In the case of glial tumors and anatomically inaccessible
   tumors, the most recent archival tissue is required.

   4. Male or female patients ≥18 years of age.

   5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.

   6. Female patients of childbearing potential must have a negative serum beta‑human
   chorionic gonadotropin (β-hCG) pregnancy test within 28 days prior to the start of
   study drug. For clinical sites in the UK, pregnancy testing must occur within 7 days
   prior to the start of study drug.

   7. Patients of reproductive potential must agree to follow the contraception requirements
   outlined in Section 6.8.11.

   8. The patient is capable of understanding and complying with the protocol and has signed
   the informed consent document. A signed informed consent form must be obtained before
   any study‑specific procedures are performed. Standard procedures performed as part of
   the practice of medicine prior to consent (eg, imaging, physical exam) can be used to
   determine eligibility if completed within 28 days prior to the initial dose of study
   drug.

   9. Patients with solid tumors must have at least 1 measurable lesion according to RECIST
   Version 1.1 (non-nodal lesions must be ≥1.0 cm in the long axis or ≥double the slice
   thickness in the long axis; nodal lesions must be ≥1.5 cm in the short axis) or
   Response Assessment in Neuro-Oncology Criteria (RANO).

   a) A non-brain lesion in a previously irradiated area is eligible to be considered as
   measurable disease as long as there is objective evidence of progression of the lesion
   before study enrollment.

10. Adequate organ function and bone marrow function as indicated by the following central
   laboratory screening assessments performed within 14 days prior to the first dose of
   study drug. Local laboratory values obtained after screening and prior to Cycle 1 Day
   1 dosing that do not meet the criteria below must be discussed with the Sponsor:

      1. Solid Tumor Patients: Bone Marrow Function: Absolute neutrophil count (ANC)
      ≥1500/μL; hemoglobin ≥9 g/dL; platelet count ≥75,000/μL.

      2. All Patients:

   i. Hepatic Function: Serum direct bilirubin ≤1.5 times the upper limit of normal (ULN)
   (≤3 × ULN if this elevation is solely due to ASM/MCL); aspartate transaminase
   (AST)/alanine transaminase (ALT), ≤3 × ULN (≤5 × ULN in the presence of hepatic
   metastases or if this elevation is solely due to ASM/MCL).

   ii. Renal Function: Serum creatinine ≤2.0 × ULN or creatinine clearance ≥50 mL/min
   based either on urine collection or Cockcroft Gault estimation.

   iii. Coagulation Profile: Prothrombin time (PT) - international normalized ratio
   (INR)/partial thromboplastin time (PTT) ≤1.5 × ULN. Patients on a stable, maintenance
   regimen of anticoagulant therapy for at least 30 days prior to study drug
   administration may have PT/INR measurements >1.5 × ULN if, in the opinion of the
   Investigator, the patient is suitable for the study. An adequate rationale must be
   provided to the Sponsor prior to enrollment.

   c) SM patients with one or more inadequate organ function laboratory value may be
   eligible if both the Investigator and Sponsor deem it to be disease-related and the
   abnormality qualifies as a C-Finding (see Appendix 10.5).

11. Resolution of all toxicities from prior therapy to ≤Grade 1 (or baseline) within 1
   week prior to the first dose of study drug (excluding alopecia and ≤Grade 3 clinically
   asymptomatic lipase, amylase, and creatine phosphokinase laboratory abnormalities).

Exclusion Criteria (Escalation and Expansion Phases)

Patients meeting any of the following criteria will be excluded from the study:

   1. GIST patients with wild type or unknown KIT or PDGFRA status.

   2. Patients with SM or other hematologic malignancies will be excluded if the following
   apply:

      1. SM patients with wild type KIT mutational status.

      2. SM patients with neutropenia accompanied by fever or infection, or
      thrombocytopenia associated with clinically significant bleeding.

         - Patients with an infection that is well controlled with antibiotics are
         eligible if there is an immediate need for treatment

      3. SM-AHN patients diagnosed with:

   i. SM with MDS (SM-MDS) who require treatment for MDS. ii. Patients requiring
   immediate treatment for AHN. d) Patients with leukemias, with the exception of MCL and
   CEL, that have progressed after imatinib.

   e) Eosinophilic myeloproliferative neoplasm patients: i. Lacking a mutation that is a
   known target of DCC-2618. This includes, but is not limited to, fusions/mutations of
   FGFR1, JAK2, and ABL.

   3. Has a known additional malignancy that is progressing or required active treatment
   within 3 years of the first dose of study treatment. Exceptions include basal cell
   carcinoma of the skin, squamous cell carcinoma of the skin that has undergone
   potentially curative therapy, or other in situ cancers.

   4. Treatment with anticancer therapy, including investigational therapy, within 2 weeks
   prior to the administration of study drug, with the exception of hydroxyurea that is
   allowed to control white blood cell count. For prior therapies with a half-life longer
   than 3 days, the interval must be at least 28 days prior to the first administration
   of study drug.

   5. New York Heart Association class III and IV heart disease, active ischemia or any
   other uncontrolled cardiac condition such as angina pectoris, clinically significant
   cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart
   failure.

   6. Arterial thrombotic or embolic events such as cerebrovascular accident (including
   ischemic attacks) or hemoptysis within 6 months before start of study drug.

   7. Venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg,
   pulmonary embolism) within the 3 months before start of study drug. Patients with
   venous thrombotic events ≥3 months before start of study drug on stable
   anticoagulation therapy are eligible.

   8. Baseline prolongation of the rate-corrected QT interval based on repeated
   demonstration of QT interval corrected by Fridericia's formula (QTcF) >450 ms in males
   or >470 ms in females or history of long QT interval corrected (QTc) syndrome.

   9. LVEF <50% or below the lower limit of normal (whichever is higher).

10. Major surgery within 4 weeks of the first dose of study drug; following major
   surgeries >4 weeks prior to the first dose of study drug, all surgical wounds must be
   healed and free of infection or dehiscence.

11. Any other clinically significant comorbidities, such as uncontrolled pulmonary
   disease, active infection, or any other condition, which in the judgment of the
   Investigator, could compromise compliance with the protocol, interfere with the
   interpretation of study results, or predispose the patient to safety risks.

12. Malabsorption syndrome or other illness that could affect oral absorption.

13. Known human immunodeficiency virus or active hepatitis C infection only if the patient
   is taking medications that are described in Section 5.8.2.2, active hepatitis B, or
   active hepatitis C infection.

14. If female, the patient is pregnant or lactating.

15. Known allergy or hypersensitivity to any component of the investigational drug
   product.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Justin Abuel
650-723-1367
Recruiting

A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies

The purpose of this Phase 1 study is to determine the safety, tolerability, maximum tolerated dose, and (preliminary) effectiveness of oral DCC-2618 in patients with advanced malignancies. The study will also determine the pharmacokinetic and pharmacodynamics profile of oral DCC-2618. The study will consist of an Escalation Phase in patients with advanced malignancies (to test safety and to determine the maximum tolerated dose of the study drug) followed by an Expansion Phase in select tumors (to further test the safety and tolerability and to obtain preliminary evidence of efficacy of the study drug). At Stanford we will be taking part in the expansion phase, for patients with GIST.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Deciphera Pharmaceuticals LLC

Intervention(s):

  • Drug: DCC-2618

Phase:

Phase 1

Eligibility


Inclusion Criteria (Escalation and Expansion Phases)

Patients must meet the following criteria to be eligible to enroll in the study:

   1. Patients must have histologically confirmed solid tumors or hematologic malignancies.
   Eligible patients include the following:

   a) GIST patients must have a KIT and PDGFRA mutation and must have progressed on or
   had an intolerability to at least 1 line of systemic anticancer therapy: i. Patients
   with a pre-existing resistance mutation to an approved line of therapy are eligible.
   For example, imatinib resistant mutations including KIT Exon 17 and PDGFRA D842V.

   b) SM patients must have a confirmed diagnosis (confirmed by a central independent
   pathologist) of advanced SM according to 2016 World Health Organization (WHO) criteria
   for SM and must have documented KIT mutant disease. SM patients must also have a
   normal karyotype.

   Advanced SM includes: ASM, SM-AHN, wherein the AHN does not require immediate
   alternative therapy, such as acute myeloid leukemia. AHNs that are eligible include:
   low grade myelodysplastic syndrome (MDS) with a high SM burden who require treatment
   for SM only, myeloproliferative neoplasms (MPNs), MDS/MPN, and HES/CEL], and MCL i.
   Patients with advanced SM must present with at least 1 eligible C-Finding (organ
   damage) as outlined in Table 3 of the 2013 International Working
   Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European
   Competence Network on Mastocytosis (ECNM) consensus response criteria (Appendix 10.5);
   please see below for MCL exception) (#iii).

   ii. Patients with imatinib-sensitive KIT mutations must have progressed on or were
   intolerant to a tryosine kinase inhibitor.

   iii. Patients with histopathologically-confirmed MCL without a C-finding are eligible.

   iv. Patients with symptomatic SSM are eligible. By definition, SSM patients must have
   at least 2 B-findings, and clinically significant symptom burden (eg, flushing,
   diarrhea, etc.) despite maximal treatment with approved agents to treat mediator
   symptoms, such as antihistamines and cromolyn sodium. Patients must have a normal
   karyotype.

   v. Patients with hematologic malignancies featuring clonal expansion of eosinophils
   driven by genomic alterations of KIT or PDGFR (eg, HES or CEL) must have a diagnosis
   confirmed by a central independent pathologist and are eligible if they have
   progressed on or are intolerant of imatinib therapy. Patients with de novo imatinib
   resistant mutations, such as but not limited to KIT D816V or PDGFRA D842V, are
   eligible without prior imatinib therapy.

   c) Malignant glioma patients with genomic alterations potentially conferring
   sensitivity to DCC-2618 including, but not limited to, amplification and/or mutations
   of PDGFRA and/or KIT.

   i. Patients must not require use of enzyme-inducing antiepileptic drugs. ii. Patients
   that require steroids must be on a stable dose for 2 weeks prior to the first dose of
   study drug.

   d) Other solid tumor patients that have alterations in genes encoding kinases that are
   targets of DCC-2618. This includes KIT, PDGFR (A or B), TIE2, CSF1R, and VEGFR2.
   Patients must have received approved treatments known to provide clinical benefit
   prior to study entry.

   e) If signs or symptoms suggest CNS metastases, a brain MRI must be performed to
   confirm absence of CNS disease within 1 week prior to receiving study drug.

   2. Patients with known CNS metastases may participate provided that:

      1. they are stable (ie, without evidence of progression by magnetic resonance
      imaging [MRI]) for at least 4 weeks prior to the first dose study drug (patients
      with active disease may be eligible following discussion between the Investigator
      and the Sponsor),

      2. all neurologic symptoms have been stable for 2 weeks prior to the first dose of
      study drug,

      3. patients must not require use of enzyme-inducing antiepileptic drugs,

      4. patients that require steroids must be on a stable dose for 2 weeks prior to the
      first dose of study drug.

   3. Patients with solid tumors (with the exception of glial tumors and tumors that are
   anatomically inaccessible) must have an archival tumor biopsy sample as long as no
   anticancer therapy was administered since the sample was collected; otherwise, a
   current biopsy is required. In the case of glial tumors and anatomically inaccessible
   tumors, the most recent archival tissue is required.

   4. Male or female patients ≥18 years of age.

   5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.

   6. Female patients of childbearing potential must have a negative serum beta‑human
   chorionic gonadotropin (β-hCG) pregnancy test within 28 days prior to the start of
   study drug. For clinical sites in the UK, pregnancy testing must occur within 7 days
   prior to the start of study drug.

   7. Patients of reproductive potential must agree to follow the contraception requirements
   outlined in Section 6.8.11.

   8. The patient is capable of understanding and complying with the protocol and has signed
   the informed consent document. A signed informed consent form must be obtained before
   any study‑specific procedures are performed. Standard procedures performed as part of
   the practice of medicine prior to consent (eg, imaging, physical exam) can be used to
   determine eligibility if completed within 28 days prior to the initial dose of study
   drug.

   9. Patients with solid tumors must have at least 1 measurable lesion according to RECIST
   Version 1.1 (non-nodal lesions must be ≥1.0 cm in the long axis or ≥double the slice
   thickness in the long axis; nodal lesions must be ≥1.5 cm in the short axis) or
   Response Assessment in Neuro-Oncology Criteria (RANO).

   a) A non-brain lesion in a previously irradiated area is eligible to be considered as
   measurable disease as long as there is objective evidence of progression of the lesion
   before study enrollment.

10. Adequate organ function and bone marrow function as indicated by the following central
   laboratory screening assessments performed within 14 days prior to the first dose of
   study drug. Local laboratory values obtained after screening and prior to Cycle 1 Day
   1 dosing that do not meet the criteria below must be discussed with the Sponsor:

      1. Solid Tumor Patients: Bone Marrow Function: Absolute neutrophil count (ANC)
      ≥1500/μL; hemoglobin ≥9 g/dL; platelet count ≥75,000/μL.

      2. All Patients:

   i. Hepatic Function: Serum direct bilirubin ≤1.5 times the upper limit of normal (ULN)
   (≤3 × ULN if this elevation is solely due to ASM/MCL); aspartate transaminase
   (AST)/alanine transaminase (ALT), ≤3 × ULN (≤5 × ULN in the presence of hepatic
   metastases or if this elevation is solely due to ASM/MCL).

   ii. Renal Function: Serum creatinine ≤2.0 × ULN or creatinine clearance ≥50 mL/min
   based either on urine collection or Cockcroft Gault estimation.

   iii. Coagulation Profile: Prothrombin time (PT) - international normalized ratio
   (INR)/partial thromboplastin time (PTT) ≤1.5 × ULN. Patients on a stable, maintenance
   regimen of anticoagulant therapy for at least 30 days prior to study drug
   administration may have PT/INR measurements >1.5 × ULN if, in the opinion of the
   Investigator, the patient is suitable for the study. An adequate rationale must be
   provided to the Sponsor prior to enrollment.

   c) SM patients with one or more inadequate organ function laboratory value may be
   eligible if both the Investigator and Sponsor deem it to be disease-related and the
   abnormality qualifies as a C-Finding (see Appendix 10.5).

11. Resolution of all toxicities from prior therapy to ≤Grade 1 (or baseline) within 1
   week prior to the first dose of study drug (excluding alopecia and ≤Grade 3 clinically
   asymptomatic lipase, amylase, and creatine phosphokinase laboratory abnormalities).

Exclusion Criteria (Escalation and Expansion Phases)

Patients meeting any of the following criteria will be excluded from the study:

   1. GIST patients with wild type or unknown KIT or PDGFRA status.

   2. Patients with SM or other hematologic malignancies will be excluded if the following
   apply:

      1. SM patients with wild type KIT mutational status.

      2. SM patients with neutropenia accompanied by fever or infection, or
      thrombocytopenia associated with clinically significant bleeding.

         - Patients with an infection that is well controlled with antibiotics are
         eligible if there is an immediate need for treatment

      3. SM-AHN patients diagnosed with:

   i. SM with MDS (SM-MDS) who require treatment for MDS. ii. Patients requiring
   immediate treatment for AHN. d) Patients with leukemias, with the exception of MCL and
   CEL, that have progressed after imatinib.

   e) Eosinophilic myeloproliferative neoplasm patients: i. Lacking a mutation that is a
   known target of DCC-2618. This includes, but is not limited to, fusions/mutations of
   FGFR1, JAK2, and ABL.

   3. Has a known additional malignancy that is progressing or required active treatment
   within 3 years of the first dose of study treatment. Exceptions include basal cell
   carcinoma of the skin, squamous cell carcinoma of the skin that has undergone
   potentially curative therapy, or other in situ cancers.

   4. Treatment with anticancer therapy, including investigational therapy, within 2 weeks
   prior to the administration of study drug, with the exception of hydroxyurea that is
   allowed to control white blood cell count. For prior therapies with a half-life longer
   than 3 days, the interval must be at least 28 days prior to the first administration
   of study drug.

   5. New York Heart Association class III and IV heart disease, active ischemia or any
   other uncontrolled cardiac condition such as angina pectoris, clinically significant
   cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart
   failure.

   6. Arterial thrombotic or embolic events such as cerebrovascular accident (including
   ischemic attacks) or hemoptysis within 6 months before start of study drug.

   7. Venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg,
   pulmonary embolism) within the 3 months before start of study drug. Patients with
   venous thrombotic events ≥3 months before start of study drug on stable
   anticoagulation therapy are eligible.

   8. Baseline prolongation of the rate-corrected QT interval based on repeated
   demonstration of QT interval corrected by Fridericia's formula (QTcF) >450 ms in males
   or >470 ms in females or history of long QT interval corrected (QTc) syndrome.

   9. LVEF <50% or below the lower limit of normal (whichever is higher).

10. Major surgery within 4 weeks of the first dose of study drug; following major
   surgeries >4 weeks prior to the first dose of study drug, all surgical wounds must be
   healed and free of infection or dehiscence.

11. Any other clinically significant comorbidities, such as uncontrolled pulmonary
   disease, active infection, or any other condition, which in the judgment of the
   Investigator, could compromise compliance with the protocol, interfere with the
   interpretation of study results, or predispose the patient to safety risks.

12. Malabsorption syndrome or other illness that could affect oral absorption.

13. Known human immunodeficiency virus or active hepatitis C infection only if the patient
   is taking medications that are described in Section 5.8.2.2, active hepatitis B, or
   active hepatitis C infection.

14. If female, the patient is pregnant or lactating.

15. Known allergy or hypersensitivity to any component of the investigational drug
   product.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Justin Abuel
650-723-1367
Recruiting

A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies

The purpose of this Phase 1 study is to determine the safety, tolerability, maximum tolerated dose, and (preliminary) effectiveness of oral DCC-2618 in patients with advanced malignancies. The study will also determine the pharmacokinetic and pharmacodynamics profile of oral DCC-2618. The study will consist of an Escalation Phase in patients with advanced malignancies (to test safety and to determine the maximum tolerated dose of the study drug) followed by an Expansion Phase in select tumors (to further test the safety and tolerability and to obtain preliminary evidence of efficacy of the study drug). At Stanford we will be taking part in the expansion phase, for patients with GIST.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Deciphera Pharmaceuticals LLC

Intervention(s):

  • Drug: DCC-2618

Phase:

Phase 1

Eligibility


Inclusion Criteria (Escalation and Expansion Phases)

Patients must meet the following criteria to be eligible to enroll in the study:

   1. Patients must have histologically confirmed solid tumors or hematologic malignancies.
   Eligible patients include the following:

   a) GIST patients must have a KIT and PDGFRA mutation and must have progressed on or
   had an intolerability to at least 1 line of systemic anticancer therapy: i. Patients
   with a pre-existing resistance mutation to an approved line of therapy are eligible.
   For example, imatinib resistant mutations including KIT Exon 17 and PDGFRA D842V.

   b) SM patients must have a confirmed diagnosis (confirmed by a central independent
   pathologist) of advanced SM according to 2016 World Health Organization (WHO) criteria
   for SM and must have documented KIT mutant disease. SM patients must also have a
   normal karyotype.

   Advanced SM includes: ASM, SM-AHN, wherein the AHN does not require immediate
   alternative therapy, such as acute myeloid leukemia. AHNs that are eligible include:
   low grade myelodysplastic syndrome (MDS) with a high SM burden who require treatment
   for SM only, myeloproliferative neoplasms (MPNs), MDS/MPN, and HES/CEL], and MCL i.
   Patients with advanced SM must present with at least 1 eligible C-Finding (organ
   damage) as outlined in Table 3 of the 2013 International Working
   Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European
   Competence Network on Mastocytosis (ECNM) consensus response criteria (Appendix 10.5);
   please see below for MCL exception) (#iii).

   ii. Patients with imatinib-sensitive KIT mutations must have progressed on or were
   intolerant to a tryosine kinase inhibitor.

   iii. Patients with histopathologically-confirmed MCL without a C-finding are eligible.

   iv. Patients with symptomatic SSM are eligible. By definition, SSM patients must have
   at least 2 B-findings, and clinically significant symptom burden (eg, flushing,
   diarrhea, etc.) despite maximal treatment with approved agents to treat mediator
   symptoms, such as antihistamines and cromolyn sodium. Patients must have a normal
   karyotype.

   v. Patients with hematologic malignancies featuring clonal expansion of eosinophils
   driven by genomic alterations of KIT or PDGFR (eg, HES or CEL) must have a diagnosis
   confirmed by a central independent pathologist and are eligible if they have
   progressed on or are intolerant of imatinib therapy. Patients with de novo imatinib
   resistant mutations, such as but not limited to KIT D816V or PDGFRA D842V, are
   eligible without prior imatinib therapy.

   c) Malignant glioma patients with genomic alterations potentially conferring
   sensitivity to DCC-2618 including, but not limited to, amplification and/or mutations
   of PDGFRA and/or KIT.

   i. Patients must not require use of enzyme-inducing antiepileptic drugs. ii. Patients
   that require steroids must be on a stable dose for 2 weeks prior to the first dose of
   study drug.

   d) Other solid tumor patients that have alterations in genes encoding kinases that are
   targets of DCC-2618. This includes KIT, PDGFR (A or B), TIE2, CSF1R, and VEGFR2.
   Patients must have received approved treatments known to provide clinical benefit
   prior to study entry.

   e) If signs or symptoms suggest CNS metastases, a brain MRI must be performed to
   confirm absence of CNS disease within 1 week prior to receiving study drug.

   2. Patients with known CNS metastases may participate provided that:

      1. they are stable (ie, without evidence of progression by magnetic resonance
      imaging [MRI]) for at least 4 weeks prior to the first dose study drug (patients
      with active disease may be eligible following discussion between the Investigator
      and the Sponsor),

      2. all neurologic symptoms have been stable for 2 weeks prior to the first dose of
      study drug,

      3. patients must not require use of enzyme-inducing antiepileptic drugs,

      4. patients that require steroids must be on a stable dose for 2 weeks prior to the
      first dose of study drug.

   3. Patients with solid tumors (with the exception of glial tumors and tumors that are
   anatomically inaccessible) must have an archival tumor biopsy sample as long as no
   anticancer therapy was administered since the sample was collected; otherwise, a
   current biopsy is required. In the case of glial tumors and anatomically inaccessible
   tumors, the most recent archival tissue is required.

   4. Male or female patients ≥18 years of age.

   5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.

   6. Female patients of childbearing potential must have a negative serum beta‑human
   chorionic gonadotropin (β-hCG) pregnancy test within 28 days prior to the start of
   study drug. For clinical sites in the UK, pregnancy testing must occur within 7 days
   prior to the start of study drug.

   7. Patients of reproductive potential must agree to follow the contraception requirements
   outlined in Section 6.8.11.

   8. The patient is capable of understanding and complying with the protocol and has signed
   the informed consent document. A signed informed consent form must be obtained before
   any study‑specific procedures are performed. Standard procedures performed as part of
   the practice of medicine prior to consent (eg, imaging, physical exam) can be used to
   determine eligibility if completed within 28 days prior to the initial dose of study
   drug.

   9. Patients with solid tumors must have at least 1 measurable lesion according to RECIST
   Version 1.1 (non-nodal lesions must be ≥1.0 cm in the long axis or ≥double the slice
   thickness in the long axis; nodal lesions must be ≥1.5 cm in the short axis) or
   Response Assessment in Neuro-Oncology Criteria (RANO).

   a) A non-brain lesion in a previously irradiated area is eligible to be considered as
   measurable disease as long as there is objective evidence of progression of the lesion
   before study enrollment.

10. Adequate organ function and bone marrow function as indicated by the following central
   laboratory screening assessments performed within 14 days prior to the first dose of
   study drug. Local laboratory values obtained after screening and prior to Cycle 1 Day
   1 dosing that do not meet the criteria below must be discussed with the Sponsor:

      1. Solid Tumor Patients: Bone Marrow Function: Absolute neutrophil count (ANC)
      ≥1500/μL; hemoglobin ≥9 g/dL; platelet count ≥75,000/μL.

      2. All Patients:

   i. Hepatic Function: Serum direct bilirubin ≤1.5 times the upper limit of normal (ULN)
   (≤3 × ULN if this elevation is solely due to ASM/MCL); aspartate transaminase
   (AST)/alanine transaminase (ALT), ≤3 × ULN (≤5 × ULN in the presence of hepatic
   metastases or if this elevation is solely due to ASM/MCL).

   ii. Renal Function: Serum creatinine ≤2.0 × ULN or creatinine clearance ≥50 mL/min
   based either on urine collection or Cockcroft Gault estimation.

   iii. Coagulation Profile: Prothrombin time (PT) - international normalized ratio
   (INR)/partial thromboplastin time (PTT) ≤1.5 × ULN. Patients on a stable, maintenance
   regimen of anticoagulant therapy for at least 30 days prior to study drug
   administration may have PT/INR measurements >1.5 × ULN if, in the opinion of the
   Investigator, the patient is suitable for the study. An adequate rationale must be
   provided to the Sponsor prior to enrollment.

   c) SM patients with one or more inadequate organ function laboratory value may be
   eligible if both the Investigator and Sponsor deem it to be disease-related and the
   abnormality qualifies as a C-Finding (see Appendix 10.5).

11. Resolution of all toxicities from prior therapy to ≤Grade 1 (or baseline) within 1
   week prior to the first dose of study drug (excluding alopecia and ≤Grade 3 clinically
   asymptomatic lipase, amylase, and creatine phosphokinase laboratory abnormalities).

Exclusion Criteria (Escalation and Expansion Phases)

Patients meeting any of the following criteria will be excluded from the study:

   1. GIST patients with wild type or unknown KIT or PDGFRA status.

   2. Patients with SM or other hematologic malignancies will be excluded if the following
   apply:

      1. SM patients with wild type KIT mutational status.

      2. SM patients with neutropenia accompanied by fever or infection, or
      thrombocytopenia associated with clinically significant bleeding.

         - Patients with an infection that is well controlled with antibiotics are
         eligible if there is an immediate need for treatment

      3. SM-AHN patients diagnosed with:

   i. SM with MDS (SM-MDS) who require treatment for MDS. ii. Patients requiring
   immediate treatment for AHN. d) Patients with leukemias, with the exception of MCL and
   CEL, that have progressed after imatinib.

   e) Eosinophilic myeloproliferative neoplasm patients: i. Lacking a mutation that is a
   known target of DCC-2618. This includes, but is not limited to, fusions/mutations of
   FGFR1, JAK2, and ABL.

   3. Has a known additional malignancy that is progressing or required active treatment
   within 3 years of the first dose of study treatment. Exceptions include basal cell
   carcinoma of the skin, squamous cell carcinoma of the skin that has undergone
   potentially curative therapy, or other in situ cancers.

   4. Treatment with anticancer therapy, including investigational therapy, within 2 weeks
   prior to the administration of study drug, with the exception of hydroxyurea that is
   allowed to control white blood cell count. For prior therapies with a half-life longer
   than 3 days, the interval must be at least 28 days prior to the first administration
   of study drug.

   5. New York Heart Association class III and IV heart disease, active ischemia or any
   other uncontrolled cardiac condition such as angina pectoris, clinically significant
   cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart
   failure.

   6. Arterial thrombotic or embolic events such as cerebrovascular accident (including
   ischemic attacks) or hemoptysis within 6 months before start of study drug.

   7. Venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg,
   pulmonary embolism) within the 3 months before start of study drug. Patients with
   venous thrombotic events ≥3 months before start of study drug on stable
   anticoagulation therapy are eligible.

   8. Baseline prolongation of the rate-corrected QT interval based on repeated
   demonstration of QT interval corrected by Fridericia's formula (QTcF) >450 ms in males
   or >470 ms in females or history of long QT interval corrected (QTc) syndrome.

   9. LVEF <50% or below the lower limit of normal (whichever is higher).

10. Major surgery within 4 weeks of the first dose of study drug; following major
   surgeries >4 weeks prior to the first dose of study drug, all surgical wounds must be
   healed and free of infection or dehiscence.

11. Any other clinically significant comorbidities, such as uncontrolled pulmonary
   disease, active infection, or any other condition, which in the judgment of the
   Investigator, could compromise compliance with the protocol, interfere with the
   interpretation of study results, or predispose the patient to safety risks.

12. Malabsorption syndrome or other illness that could affect oral absorption.

13. Known human immunodeficiency virus or active hepatitis C infection only if the patient
   is taking medications that are described in Section 5.8.2.2, active hepatitis B, or
   active hepatitis C infection.

14. If female, the patient is pregnant or lactating.

15. Known allergy or hypersensitivity to any component of the investigational drug
   product.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Justin Abuel
650-723-1367
Recruiting

A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies

The purpose of this Phase 1 study is to determine the safety, tolerability, maximum tolerated dose, and (preliminary) effectiveness of oral DCC-2618 in patients with advanced malignancies. The study will also determine the pharmacokinetic and pharmacodynamics profile of oral DCC-2618. The study will consist of an Escalation Phase in patients with advanced malignancies (to test safety and to determine the maximum tolerated dose of the study drug) followed by an Expansion Phase in select tumors (to further test the safety and tolerability and to obtain preliminary evidence of efficacy of the study drug). At Stanford we will be taking part in the expansion phase, for patients with GIST.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Deciphera Pharmaceuticals LLC

Intervention(s):

  • Drug: DCC-2618

Phase:

Phase 1

Eligibility


Inclusion Criteria (Escalation and Expansion Phases)

Patients must meet the following criteria to be eligible to enroll in the study:

   1. Patients must have histologically confirmed solid tumors or hematologic malignancies.
   Eligible patients include the following:

   a) GIST patients must have a KIT and PDGFRA mutation and must have progressed on or
   had an intolerability to at least 1 line of systemic anticancer therapy: i. Patients
   with a pre-existing resistance mutation to an approved line of therapy are eligible.
   For example, imatinib resistant mutations including KIT Exon 17 and PDGFRA D842V.

   b) SM patients must have a confirmed diagnosis (confirmed by a central independent
   pathologist) of advanced SM according to 2016 World Health Organization (WHO) criteria
   for SM and must have documented KIT mutant disease. SM patients must also have a
   normal karyotype.

   Advanced SM includes: ASM, SM-AHN, wherein the AHN does not require immediate
   alternative therapy, such as acute myeloid leukemia. AHNs that are eligible include:
   low grade myelodysplastic syndrome (MDS) with a high SM burden who require treatment
   for SM only, myeloproliferative neoplasms (MPNs), MDS/MPN, and HES/CEL], and MCL i.
   Patients with advanced SM must present with at least 1 eligible C-Finding (organ
   damage) as outlined in Table 3 of the 2013 International Working
   Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European
   Competence Network on Mastocytosis (ECNM) consensus response criteria (Appendix 10.5);
   please see below for MCL exception) (#iii).

   ii. Patients with imatinib-sensitive KIT mutations must have progressed on or were
   intolerant to a tryosine kinase inhibitor.

   iii. Patients with histopathologically-confirmed MCL without a C-finding are eligible.

   iv. Patients with symptomatic SSM are eligible. By definition, SSM patients must have
   at least 2 B-findings, and clinically significant symptom burden (eg, flushing,
   diarrhea, etc.) despite maximal treatment with approved agents to treat mediator
   symptoms, such as antihistamines and cromolyn sodium. Patients must have a normal
   karyotype.

   v. Patients with hematologic malignancies featuring clonal expansion of eosinophils
   driven by genomic alterations of KIT or PDGFR (eg, HES or CEL) must have a diagnosis
   confirmed by a central independent pathologist and are eligible if they have
   progressed on or are intolerant of imatinib therapy. Patients with de novo imatinib
   resistant mutations, such as but not limited to KIT D816V or PDGFRA D842V, are
   eligible without prior imatinib therapy.

   c) Malignant glioma patients with genomic alterations potentially conferring
   sensitivity to DCC-2618 including, but not limited to, amplification and/or mutations
   of PDGFRA and/or KIT.

   i. Patients must not require use of enzyme-inducing antiepileptic drugs. ii. Patients
   that require steroids must be on a stable dose for 2 weeks prior to the first dose of
   study drug.

   d) Other solid tumor patients that have alterations in genes encoding kinases that are
   targets of DCC-2618. This includes KIT, PDGFR (A or B), TIE2, CSF1R, and VEGFR2.
   Patients must have received approved treatments known to provide clinical benefit
   prior to study entry.

   e) If signs or symptoms suggest CNS metastases, a brain MRI must be performed to
   confirm absence of CNS disease within 1 week prior to receiving study drug.

   2. Patients with known CNS metastases may participate provided that:

      1. they are stable (ie, without evidence of progression by magnetic resonance
      imaging [MRI]) for at least 4 weeks prior to the first dose study drug (patients
      with active disease may be eligible following discussion between the Investigator
      and the Sponsor),

      2. all neurologic symptoms have been stable for 2 weeks prior to the first dose of
      study drug,

      3. patients must not require use of enzyme-inducing antiepileptic drugs,

      4. patients that require steroids must be on a stable dose for 2 weeks prior to the
      first dose of study drug.

   3. Patients with solid tumors (with the exception of glial tumors and tumors that are
   anatomically inaccessible) must have an archival tumor biopsy sample as long as no
   anticancer therapy was administered since the sample was collected; otherwise, a
   current biopsy is required. In the case of glial tumors and anatomically inaccessible
   tumors, the most recent archival tissue is required.

   4. Male or female patients ≥18 years of age.

   5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.

   6. Female patients of childbearing potential must have a negative serum beta‑human
   chorionic gonadotropin (β-hCG) pregnancy test within 28 days prior to the start of
   study drug. For clinical sites in the UK, pregnancy testing must occur within 7 days
   prior to the start of study drug.

   7. Patients of reproductive potential must agree to follow the contraception requirements
   outlined in Section 6.8.11.

   8. The patient is capable of understanding and complying with the protocol and has signed
   the informed consent document. A signed informed consent form must be obtained before
   any study‑specific procedures are performed. Standard procedures performed as part of
   the practice of medicine prior to consent (eg, imaging, physical exam) can be used to
   determine eligibility if completed within 28 days prior to the initial dose of study
   drug.

   9. Patients with solid tumors must have at least 1 measurable lesion according to RECIST
   Version 1.1 (non-nodal lesions must be ≥1.0 cm in the long axis or ≥double the slice
   thickness in the long axis; nodal lesions must be ≥1.5 cm in the short axis) or
   Response Assessment in Neuro-Oncology Criteria (RANO).

   a) A non-brain lesion in a previously irradiated area is eligible to be considered as
   measurable disease as long as there is objective evidence of progression of the lesion
   before study enrollment.

10. Adequate organ function and bone marrow function as indicated by the following central
   laboratory screening assessments performed within 14 days prior to the first dose of
   study drug. Local laboratory values obtained after screening and prior to Cycle 1 Day
   1 dosing that do not meet the criteria below must be discussed with the Sponsor:

      1. Solid Tumor Patients: Bone Marrow Function: Absolute neutrophil count (ANC)
      ≥1500/μL; hemoglobin ≥9 g/dL; platelet count ≥75,000/μL.

      2. All Patients:

   i. Hepatic Function: Serum direct bilirubin ≤1.5 times the upper limit of normal (ULN)
   (≤3 × ULN if this elevation is solely due to ASM/MCL); aspartate transaminase
   (AST)/alanine transaminase (ALT), ≤3 × ULN (≤5 × ULN in the presence of hepatic
   metastases or if this elevation is solely due to ASM/MCL).

   ii. Renal Function: Serum creatinine ≤2.0 × ULN or creatinine clearance ≥50 mL/min
   based either on urine collection or Cockcroft Gault estimation.

   iii. Coagulation Profile: Prothrombin time (PT) - international normalized ratio
   (INR)/partial thromboplastin time (PTT) ≤1.5 × ULN. Patients on a stable, maintenance
   regimen of anticoagulant therapy for at least 30 days prior to study drug
   administration may have PT/INR measurements >1.5 × ULN if, in the opinion of the
   Investigator, the patient is suitable for the study. An adequate rationale must be
   provided to the Sponsor prior to enrollment.

   c) SM patients with one or more inadequate organ function laboratory value may be
   eligible if both the Investigator and Sponsor deem it to be disease-related and the
   abnormality qualifies as a C-Finding (see Appendix 10.5).

11. Resolution of all toxicities from prior therapy to ≤Grade 1 (or baseline) within 1
   week prior to the first dose of study drug (excluding alopecia and ≤Grade 3 clinically
   asymptomatic lipase, amylase, and creatine phosphokinase laboratory abnormalities).

Exclusion Criteria (Escalation and Expansion Phases)

Patients meeting any of the following criteria will be excluded from the study:

   1. GIST patients with wild type or unknown KIT or PDGFRA status.

   2. Patients with SM or other hematologic malignancies will be excluded if the following
   apply:

      1. SM patients with wild type KIT mutational status.

      2. SM patients with neutropenia accompanied by fever or infection, or
      thrombocytopenia associated with clinically significant bleeding.

         - Patients with an infection that is well controlled with antibiotics are
         eligible if there is an immediate need for treatment

      3. SM-AHN patients diagnosed with:

   i. SM with MDS (SM-MDS) who require treatment for MDS. ii. Patients requiring
   immediate treatment for AHN. d) Patients with leukemias, with the exception of MCL and
   CEL, that have progressed after imatinib.

   e) Eosinophilic myeloproliferative neoplasm patients: i. Lacking a mutation that is a
   known target of DCC-2618. This includes, but is not limited to, fusions/mutations of
   FGFR1, JAK2, and ABL.

   3. Has a known additional malignancy that is progressing or required active treatment
   within 3 years of the first dose of study treatment. Exceptions include basal cell
   carcinoma of the skin, squamous cell carcinoma of the skin that has undergone
   potentially curative therapy, or other in situ cancers.

   4. Treatment with anticancer therapy, including investigational therapy, within 2 weeks
   prior to the administration of study drug, with the exception of hydroxyurea that is
   allowed to control white blood cell count. For prior therapies with a half-life longer
   than 3 days, the interval must be at least 28 days prior to the first administration
   of study drug.

   5. New York Heart Association class III and IV heart disease, active ischemia or any
   other uncontrolled cardiac condition such as angina pectoris, clinically significant
   cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart
   failure.

   6. Arterial thrombotic or embolic events such as cerebrovascular accident (including
   ischemic attacks) or hemoptysis within 6 months before start of study drug.

   7. Venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg,
   pulmonary embolism) within the 3 months before start of study drug. Patients with
   venous thrombotic events ≥3 months before start of study drug on stable
   anticoagulation therapy are eligible.

   8. Baseline prolongation of the rate-corrected QT interval based on repeated
   demonstration of QT interval corrected by Fridericia's formula (QTcF) >450 ms in males
   or >470 ms in females or history of long QT interval corrected (QTc) syndrome.

   9. LVEF <50% or below the lower limit of normal (whichever is higher).

10. Major surgery within 4 weeks of the first dose of study drug; following major
   surgeries >4 weeks prior to the first dose of study drug, all surgical wounds must be
   healed and free of infection or dehiscence.

11. Any other clinically significant comorbidities, such as uncontrolled pulmonary
   disease, active infection, or any other condition, which in the judgment of the
   Investigator, could compromise compliance with the protocol, interfere with the
   interpretation of study results, or predispose the patient to safety risks.

12. Malabsorption syndrome or other illness that could affect oral absorption.

13. Known human immunodeficiency virus or active hepatitis C infection only if the patient
   is taking medications that are described in Section 5.8.2.2, active hepatitis B, or
   active hepatitis C infection.

14. If female, the patient is pregnant or lactating.

15. Known allergy or hypersensitivity to any component of the investigational drug
   product.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Justin Abuel
650-723-1367
Recruiting

A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies

The purpose of this Phase 1 study is to determine the safety, tolerability, maximum tolerated dose, and (preliminary) effectiveness of oral DCC-2618 in patients with advanced malignancies. The study will also determine the pharmacokinetic and pharmacodynamics profile of oral DCC-2618. The study will consist of an Escalation Phase in patients with advanced malignancies (to test safety and to determine the maximum tolerated dose of the study drug) followed by an Expansion Phase in select tumors (to further test the safety and tolerability and to obtain preliminary evidence of efficacy of the study drug). At Stanford we will be taking part in the expansion phase, for patients with GIST.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Deciphera Pharmaceuticals LLC

Intervention(s):

  • Drug: DCC-2618

Phase:

Phase 1

Eligibility


Inclusion Criteria (Escalation and Expansion Phases)

Patients must meet the following criteria to be eligible to enroll in the study:

   1. Patients must have histologically confirmed solid tumors or hematologic malignancies.
   Eligible patients include the following:

   a) GIST patients must have a KIT and PDGFRA mutation and must have progressed on or
   had an intolerability to at least 1 line of systemic anticancer therapy: i. Patients
   with a pre-existing resistance mutation to an approved line of therapy are eligible.
   For example, imatinib resistant mutations including KIT Exon 17 and PDGFRA D842V.

   b) SM patients must have a confirmed diagnosis (confirmed by a central independent
   pathologist) of advanced SM according to 2016 World Health Organization (WHO) criteria
   for SM and must have documented KIT mutant disease. SM patients must also have a
   normal karyotype.

   Advanced SM includes: ASM, SM-AHN, wherein the AHN does not require immediate
   alternative therapy, such as acute myeloid leukemia. AHNs that are eligible include:
   low grade myelodysplastic syndrome (MDS) with a high SM burden who require treatment
   for SM only, myeloproliferative neoplasms (MPNs), MDS/MPN, and HES/CEL], and MCL i.
   Patients with advanced SM must present with at least 1 eligible C-Finding (organ
   damage) as outlined in Table 3 of the 2013 International Working
   Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European
   Competence Network on Mastocytosis (ECNM) consensus response criteria (Appendix 10.5);
   please see below for MCL exception) (#iii).

   ii. Patients with imatinib-sensitive KIT mutations must have progressed on or were
   intolerant to a tryosine kinase inhibitor.

   iii. Patients with histopathologically-confirmed MCL without a C-finding are eligible.

   iv. Patients with symptomatic SSM are eligible. By definition, SSM patients must have
   at least 2 B-findings, and clinically significant symptom burden (eg, flushing,
   diarrhea, etc.) despite maximal treatment with approved agents to treat mediator
   symptoms, such as antihistamines and cromolyn sodium. Patients must have a normal
   karyotype.

   v. Patients with hematologic malignancies featuring clonal expansion of eosinophils
   driven by genomic alterations of KIT or PDGFR (eg, HES or CEL) must have a diagnosis
   confirmed by a central independent pathologist and are eligible if they have
   progressed on or are intolerant of imatinib therapy. Patients with de novo imatinib
   resistant mutations, such as but not limited to KIT D816V or PDGFRA D842V, are
   eligible without prior imatinib therapy.

   c) Malignant glioma patients with genomic alterations potentially conferring
   sensitivity to DCC-2618 including, but not limited to, amplification and/or mutations
   of PDGFRA and/or KIT.

   i. Patients must not require use of enzyme-inducing antiepileptic drugs. ii. Patients
   that require steroids must be on a stable dose for 2 weeks prior to the first dose of
   study drug.

   d) Other solid tumor patients that have alterations in genes encoding kinases that are
   targets of DCC-2618. This includes KIT, PDGFR (A or B), TIE2, CSF1R, and VEGFR2.
   Patients must have received approved treatments known to provide clinical benefit
   prior to study entry.

   e) If signs or symptoms suggest CNS metastases, a brain MRI must be performed to
   confirm absence of CNS disease within 1 week prior to receiving study drug.

   2. Patients with known CNS metastases may participate provided that:

      1. they are stable (ie, without evidence of progression by magnetic resonance
      imaging [MRI]) for at least 4 weeks prior to the first dose study drug (patients
      with active disease may be eligible following discussion between the Investigator
      and the Sponsor),

      2. all neurologic symptoms have been stable for 2 weeks prior to the first dose of
      study drug,

      3. patients must not require use of enzyme-inducing antiepileptic drugs,

      4. patients that require steroids must be on a stable dose for 2 weeks prior to the
      first dose of study drug.

   3. Patients with solid tumors (with the exception of glial tumors and tumors that are
   anatomically inaccessible) must have an archival tumor biopsy sample as long as no
   anticancer therapy was administered since the sample was collected; otherwise, a
   current biopsy is required. In the case of glial tumors and anatomically inaccessible
   tumors, the most recent archival tissue is required.

   4. Male or female patients ≥18 years of age.

   5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.

   6. Female patients of childbearing potential must have a negative serum beta‑human
   chorionic gonadotropin (β-hCG) pregnancy test within 28 days prior to the start of
   study drug. For clinical sites in the UK, pregnancy testing must occur within 7 days
   prior to the start of study drug.

   7. Patients of reproductive potential must agree to follow the contraception requirements
   outlined in Section 6.8.11.

   8. The patient is capable of understanding and complying with the protocol and has signed
   the informed consent document. A signed informed consent form must be obtained before
   any study‑specific procedures are performed. Standard procedures performed as part of
   the practice of medicine prior to consent (eg, imaging, physical exam) can be used to
   determine eligibility if completed within 28 days prior to the initial dose of study
   drug.

   9. Patients with solid tumors must have at least 1 measurable lesion according to RECIST
   Version 1.1 (non-nodal lesions must be ≥1.0 cm in the long axis or ≥double the slice
   thickness in the long axis; nodal lesions must be ≥1.5 cm in the short axis) or
   Response Assessment in Neuro-Oncology Criteria (RANO).

   a) A non-brain lesion in a previously irradiated area is eligible to be considered as
   measurable disease as long as there is objective evidence of progression of the lesion
   before study enrollment.

10. Adequate organ function and bone marrow function as indicated by the following central
   laboratory screening assessments performed within 14 days prior to the first dose of
   study drug. Local laboratory values obtained after screening and prior to Cycle 1 Day
   1 dosing that do not meet the criteria below must be discussed with the Sponsor:

      1. Solid Tumor Patients: Bone Marrow Function: Absolute neutrophil count (ANC)
      ≥1500/μL; hemoglobin ≥9 g/dL; platelet count ≥75,000/μL.

      2. All Patients:

   i. Hepatic Function: Serum direct bilirubin ≤1.5 times the upper limit of normal (ULN)
   (≤3 × ULN if this elevation is solely due to ASM/MCL); aspartate transaminase
   (AST)/alanine transaminase (ALT), ≤3 × ULN (≤5 × ULN in the presence of hepatic
   metastases or if this elevation is solely due to ASM/MCL).

   ii. Renal Function: Serum creatinine ≤2.0 × ULN or creatinine clearance ≥50 mL/min
   based either on urine collection or Cockcroft Gault estimation.

   iii. Coagulation Profile: Prothrombin time (PT) - international normalized ratio
   (INR)/partial thromboplastin time (PTT) ≤1.5 × ULN. Patients on a stable, maintenance
   regimen of anticoagulant therapy for at least 30 days prior to study drug
   administration may have PT/INR measurements >1.5 × ULN if, in the opinion of the
   Investigator, the patient is suitable for the study. An adequate rationale must be
   provided to the Sponsor prior to enrollment.

   c) SM patients with one or more inadequate organ function laboratory value may be
   eligible if both the Investigator and Sponsor deem it to be disease-related and the
   abnormality qualifies as a C-Finding (see Appendix 10.5).

11. Resolution of all toxicities from prior therapy to ≤Grade 1 (or baseline) within 1
   week prior to the first dose of study drug (excluding alopecia and ≤Grade 3 clinically
   asymptomatic lipase, amylase, and creatine phosphokinase laboratory abnormalities).

Exclusion Criteria (Escalation and Expansion Phases)

Patients meeting any of the following criteria will be excluded from the study:

   1. GIST patients with wild type or unknown KIT or PDGFRA status.

   2. Patients with SM or other hematologic malignancies will be excluded if the following
   apply:

      1. SM patients with wild type KIT mutational status.

      2. SM patients with neutropenia accompanied by fever or infection, or
      thrombocytopenia associated with clinically significant bleeding.

         - Patients with an infection that is well controlled with antibiotics are
         eligible if there is an immediate need for treatment

      3. SM-AHN patients diagnosed with:

   i. SM with MDS (SM-MDS) who require treatment for MDS. ii. Patients requiring
   immediate treatment for AHN. d) Patients with leukemias, with the exception of MCL and
   CEL, that have progressed after imatinib.

   e) Eosinophilic myeloproliferative neoplasm patients: i. Lacking a mutation that is a
   known target of DCC-2618. This includes, but is not limited to, fusions/mutations of
   FGFR1, JAK2, and ABL.

   3. Has a known additional malignancy that is progressing or required active treatment
   within 3 years of the first dose of study treatment. Exceptions include basal cell
   carcinoma of the skin, squamous cell carcinoma of the skin that has undergone
   potentially curative therapy, or other in situ cancers.

   4. Treatment with anticancer therapy, including investigational therapy, within 2 weeks
   prior to the administration of study drug, with the exception of hydroxyurea that is
   allowed to control white blood cell count. For prior therapies with a half-life longer
   than 3 days, the interval must be at least 28 days prior to the first administration
   of study drug.

   5. New York Heart Association class III and IV heart disease, active ischemia or any
   other uncontrolled cardiac condition such as angina pectoris, clinically significant
   cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart
   failure.

   6. Arterial thrombotic or embolic events such as cerebrovascular accident (including
   ischemic attacks) or hemoptysis within 6 months before start of study drug.

   7. Venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg,
   pulmonary embolism) within the 3 months before start of study drug. Patients with
   venous thrombotic events ≥3 months before start of study drug on stable
   anticoagulation therapy are eligible.

   8. Baseline prolongation of the rate-corrected QT interval based on repeated
   demonstration of QT interval corrected by Fridericia's formula (QTcF) >450 ms in males
   or >470 ms in females or history of long QT interval corrected (QTc) syndrome.

   9. LVEF <50% or below the lower limit of normal (whichever is higher).

10. Major surgery within 4 weeks of the first dose of study drug; following major
   surgeries >4 weeks prior to the first dose of study drug, all surgical wounds must be
   healed and free of infection or dehiscence.

11. Any other clinically significant comorbidities, such as uncontrolled pulmonary
   disease, active infection, or any other condition, which in the judgment of the
   Investigator, could compromise compliance with the protocol, interfere with the
   interpretation of study results, or predispose the patient to safety risks.

12. Malabsorption syndrome or other illness that could affect oral absorption.

13. Known human immunodeficiency virus or active hepatitis C infection only if the patient
   is taking medications that are described in Section 5.8.2.2, active hepatitis B, or
   active hepatitis C infection.

14. If female, the patient is pregnant or lactating.

15. Known allergy or hypersensitivity to any component of the investigational drug
   product.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Justin Abuel
650-723-1367
Recruiting

A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies

The purpose of this Phase 1 study is to determine the safety, tolerability, maximum tolerated dose, and (preliminary) effectiveness of oral DCC-2618 in patients with advanced malignancies. The study will also determine the pharmacokinetic and pharmacodynamics profile of oral DCC-2618. The study will consist of an Escalation Phase in patients with advanced malignancies (to test safety and to determine the maximum tolerated dose of the study drug) followed by an Expansion Phase in select tumors (to further test the safety and tolerability and to obtain preliminary evidence of efficacy of the study drug). At Stanford we will be taking part in the expansion phase, for patients with GIST.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Deciphera Pharmaceuticals LLC

Intervention(s):

  • Drug: DCC-2618

Phase:

Phase 1

Eligibility


Inclusion Criteria (Escalation and Expansion Phases)

Patients must meet the following criteria to be eligible to enroll in the study:

   1. Patients must have histologically confirmed solid tumors or hematologic malignancies.
   Eligible patients include the following:

   a) GIST patients must have a KIT and PDGFRA mutation and must have progressed on or
   had an intolerability to at least 1 line of systemic anticancer therapy: i. Patients
   with a pre-existing resistance mutation to an approved line of therapy are eligible.
   For example, imatinib resistant mutations including KIT Exon 17 and PDGFRA D842V.

   b) SM patients must have a confirmed diagnosis (confirmed by a central independent
   pathologist) of advanced SM according to 2016 World Health Organization (WHO) criteria
   for SM and must have documented KIT mutant disease. SM patients must also have a
   normal karyotype.

   Advanced SM includes: ASM, SM-AHN, wherein the AHN does not require immediate
   alternative therapy, such as acute myeloid leukemia. AHNs that are eligible include:
   low grade myelodysplastic syndrome (MDS) with a high SM burden who require treatment
   for SM only, myeloproliferative neoplasms (MPNs), MDS/MPN, and HES/CEL], and MCL i.
   Patients with advanced SM must present with at least 1 eligible C-Finding (organ
   damage) as outlined in Table 3 of the 2013 International Working
   Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European
   Competence Network on Mastocytosis (ECNM) consensus response criteria (Appendix 10.5);
   please see below for MCL exception) (#iii).

   ii. Patients with imatinib-sensitive KIT mutations must have progressed on or were
   intolerant to a tryosine kinase inhibitor.

   iii. Patients with histopathologically-confirmed MCL without a C-finding are eligible.

   iv. Patients with symptomatic SSM are eligible. By definition, SSM patients must have
   at least 2 B-findings, and clinically significant symptom burden (eg, flushing,
   diarrhea, etc.) despite maximal treatment with approved agents to treat mediator
   symptoms, such as antihistamines and cromolyn sodium. Patients must have a normal
   karyotype.

   v. Patients with hematologic malignancies featuring clonal expansion of eosinophils
   driven by genomic alterations of KIT or PDGFR (eg, HES or CEL) must have a diagnosis
   confirmed by a central independent pathologist and are eligible if they have
   progressed on or are intolerant of imatinib therapy. Patients with de novo imatinib
   resistant mutations, such as but not limited to KIT D816V or PDGFRA D842V, are
   eligible without prior imatinib therapy.

   c) Malignant glioma patients with genomic alterations potentially conferring
   sensitivity to DCC-2618 including, but not limited to, amplification and/or mutations
   of PDGFRA and/or KIT.

   i. Patients must not require use of enzyme-inducing antiepileptic drugs. ii. Patients
   that require steroids must be on a stable dose for 2 weeks prior to the first dose of
   study drug.

   d) Other solid tumor patients that have alterations in genes encoding kinases that are
   targets of DCC-2618. This includes KIT, PDGFR (A or B), TIE2, CSF1R, and VEGFR2.
   Patients must have received approved treatments known to provide clinical benefit
   prior to study entry.

   e) If signs or symptoms suggest CNS metastases, a brain MRI must be performed to
   confirm absence of CNS disease within 1 week prior to receiving study drug.

   2. Patients with known CNS metastases may participate provided that:

      1. they are stable (ie, without evidence of progression by magnetic resonance
      imaging [MRI]) for at least 4 weeks prior to the first dose study drug (patients
      with active disease may be eligible following discussion between the Investigator
      and the Sponsor),

      2. all neurologic symptoms have been stable for 2 weeks prior to the first dose of
      study drug,

      3. patients must not require use of enzyme-inducing antiepileptic drugs,

      4. patients that require steroids must be on a stable dose for 2 weeks prior to the
      first dose of study drug.

   3. Patients with solid tumors (with the exception of glial tumors and tumors that are
   anatomically inaccessible) must have an archival tumor biopsy sample as long as no
   anticancer therapy was administered since the sample was collected; otherwise, a
   current biopsy is required. In the case of glial tumors and anatomically inaccessible
   tumors, the most recent archival tissue is required.

   4. Male or female patients ≥18 years of age.

   5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.

   6. Female patients of childbearing potential must have a negative serum beta‑human
   chorionic gonadotropin (β-hCG) pregnancy test within 28 days prior to the start of
   study drug. For clinical sites in the UK, pregnancy testing must occur within 7 days
   prior to the start of study drug.

   7. Patients of reproductive potential must agree to follow the contraception requirements
   outlined in Section 6.8.11.

   8. The patient is capable of understanding and complying with the protocol and has signed
   the informed consent document. A signed informed consent form must be obtained before
   any study‑specific procedures are performed. Standard procedures performed as part of
   the practice of medicine prior to consent (eg, imaging, physical exam) can be used to
   determine eligibility if completed within 28 days prior to the initial dose of study
   drug.

   9. Patients with solid tumors must have at least 1 measurable lesion according to RECIST
   Version 1.1 (non-nodal lesions must be ≥1.0 cm in the long axis or ≥double the slice
   thickness in the long axis; nodal lesions must be ≥1.5 cm in the short axis) or
   Response Assessment in Neuro-Oncology Criteria (RANO).

   a) A non-brain lesion in a previously irradiated area is eligible to be considered as
   measurable disease as long as there is objective evidence of progression of the lesion
   before study enrollment.

10. Adequate organ function and bone marrow function as indicated by the following central
   laboratory screening assessments performed within 14 days prior to the first dose of
   study drug. Local laboratory values obtained after screening and prior to Cycle 1 Day
   1 dosing that do not meet the criteria below must be discussed with the Sponsor:

      1. Solid Tumor Patients: Bone Marrow Function: Absolute neutrophil count (ANC)
      ≥1500/μL; hemoglobin ≥9 g/dL; platelet count ≥75,000/μL.

      2. All Patients:

   i. Hepatic Function: Serum direct bilirubin ≤1.5 times the upper limit of normal (ULN)
   (≤3 × ULN if this elevation is solely due to ASM/MCL); aspartate transaminase
   (AST)/alanine transaminase (ALT), ≤3 × ULN (≤5 × ULN in the presence of hepatic
   metastases or if this elevation is solely due to ASM/MCL).

   ii. Renal Function: Serum creatinine ≤2.0 × ULN or creatinine clearance ≥50 mL/min
   based either on urine collection or Cockcroft Gault estimation.

   iii. Coagulation Profile: Prothrombin time (PT) - international normalized ratio
   (INR)/partial thromboplastin time (PTT) ≤1.5 × ULN. Patients on a stable, maintenance
   regimen of anticoagulant therapy for at least 30 days prior to study drug
   administration may have PT/INR measurements >1.5 × ULN if, in the opinion of the
   Investigator, the patient is suitable for the study. An adequate rationale must be
   provided to the Sponsor prior to enrollment.

   c) SM patients with one or more inadequate organ function laboratory value may be
   eligible if both the Investigator and Sponsor deem it to be disease-related and the
   abnormality qualifies as a C-Finding (see Appendix 10.5).

11. Resolution of all toxicities from prior therapy to ≤Grade 1 (or baseline) within 1
   week prior to the first dose of study drug (excluding alopecia and ≤Grade 3 clinically
   asymptomatic lipase, amylase, and creatine phosphokinase laboratory abnormalities).

Exclusion Criteria (Escalation and Expansion Phases)

Patients meeting any of the following criteria will be excluded from the study:

   1. GIST patients with wild type or unknown KIT or PDGFRA status.

   2. Patients with SM or other hematologic malignancies will be excluded if the following
   apply:

      1. SM patients with wild type KIT mutational status.

      2. SM patients with neutropenia accompanied by fever or infection, or
      thrombocytopenia associated with clinically significant bleeding.

         - Patients with an infection that is well controlled with antibiotics are
         eligible if there is an immediate need for treatment

      3. SM-AHN patients diagnosed with:

   i. SM with MDS (SM-MDS) who require treatment for MDS. ii. Patients requiring
   immediate treatment for AHN. d) Patients with leukemias, with the exception of MCL and
   CEL, that have progressed after imatinib.

   e) Eosinophilic myeloproliferative neoplasm patients: i. Lacking a mutation that is a
   known target of DCC-2618. This includes, but is not limited to, fusions/mutations of
   FGFR1, JAK2, and ABL.

   3. Has a known additional malignancy that is progressing or required active treatment
   within 3 years of the first dose of study treatment. Exceptions include basal cell
   carcinoma of the skin, squamous cell carcinoma of the skin that has undergone
   potentially curative therapy, or other in situ cancers.

   4. Treatment with anticancer therapy, including investigational therapy, within 2 weeks
   prior to the administration of study drug, with the exception of hydroxyurea that is
   allowed to control white blood cell count. For prior therapies with a half-life longer
   than 3 days, the interval must be at least 28 days prior to the first administration
   of study drug.

   5. New York Heart Association class III and IV heart disease, active ischemia or any
   other uncontrolled cardiac condition such as angina pectoris, clinically significant
   cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart
   failure.

   6. Arterial thrombotic or embolic events such as cerebrovascular accident (including
   ischemic attacks) or hemoptysis within 6 months before start of study drug.

   7. Venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg,
   pulmonary embolism) within the 3 months before start of study drug. Patients with
   venous thrombotic events ≥3 months before start of study drug on stable
   anticoagulation therapy are eligible.

   8. Baseline prolongation of the rate-corrected QT interval based on repeated
   demonstration of QT interval corrected by Fridericia's formula (QTcF) >450 ms in males
   or >470 ms in females or history of long QT interval corrected (QTc) syndrome.

   9. LVEF <50% or below the lower limit of normal (whichever is higher).

10. Major surgery within 4 weeks of the first dose of study drug; following major
   surgeries >4 weeks prior to the first dose of study drug, all surgical wounds must be
   healed and free of infection or dehiscence.

11. Any other clinically significant comorbidities, such as uncontrolled pulmonary
   disease, active infection, or any other condition, which in the judgment of the
   Investigator, could compromise compliance with the protocol, interfere with the
   interpretation of study results, or predispose the patient to safety risks.

12. Malabsorption syndrome or other illness that could affect oral absorption.

13. Known human immunodeficiency virus or active hepatitis C infection only if the patient
   is taking medications that are described in Section 5.8.2.2, active hepatitis B, or
   active hepatitis C infection.

14. If female, the patient is pregnant or lactating.

15. Known allergy or hypersensitivity to any component of the investigational drug
   product.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Justin Abuel
650-723-1367
Recruiting

A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies

The purpose of this Phase 1 study is to determine the safety, tolerability, maximum tolerated dose, and (preliminary) effectiveness of oral DCC-2618 in patients with advanced malignancies. The study will also determine the pharmacokinetic and pharmacodynamics profile of oral DCC-2618. The study will consist of an Escalation Phase in patients with advanced malignancies (to test safety and to determine the maximum tolerated dose of the study drug) followed by an Expansion Phase in select tumors (to further test the safety and tolerability and to obtain preliminary evidence of efficacy of the study drug). At Stanford we will be taking part in the expansion phase, for patients with GIST.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Deciphera Pharmaceuticals LLC

Intervention(s):

  • Drug: DCC-2618

Phase:

Phase 1

Eligibility


Inclusion Criteria (Escalation and Expansion Phases)

Patients must meet the following criteria to be eligible to enroll in the study:

   1. Patients must have histologically confirmed solid tumors or hematologic malignancies.
   Eligible patients include the following:

   a) GIST patients must have a KIT and PDGFRA mutation and must have progressed on or
   had an intolerability to at least 1 line of systemic anticancer therapy: i. Patients
   with a pre-existing resistance mutation to an approved line of therapy are eligible.
   For example, imatinib resistant mutations including KIT Exon 17 and PDGFRA D842V.

   b) SM patients must have a confirmed diagnosis (confirmed by a central independent
   pathologist) of advanced SM according to 2016 World Health Organization (WHO) criteria
   for SM and must have documented KIT mutant disease. SM patients must also have a
   normal karyotype.

   Advanced SM includes: ASM, SM-AHN, wherein the AHN does not require immediate
   alternative therapy, such as acute myeloid leukemia. AHNs that are eligible include:
   low grade myelodysplastic syndrome (MDS) with a high SM burden who require treatment
   for SM only, myeloproliferative neoplasms (MPNs), MDS/MPN, and HES/CEL], and MCL i.
   Patients with advanced SM must present with at least 1 eligible C-Finding (organ
   damage) as outlined in Table 3 of the 2013 International Working
   Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European
   Competence Network on Mastocytosis (ECNM) consensus response criteria (Appendix 10.5);
   please see below for MCL exception) (#iii).

   ii. Patients with imatinib-sensitive KIT mutations must have progressed on or were
   intolerant to a tryosine kinase inhibitor.

   iii. Patients with histopathologically-confirmed MCL without a C-finding are eligible.

   iv. Patients with symptomatic SSM are eligible. By definition, SSM patients must have
   at least 2 B-findings, and clinically significant symptom burden (eg, flushing,
   diarrhea, etc.) despite maximal treatment with approved agents to treat mediator
   symptoms, such as antihistamines and cromolyn sodium. Patients must have a normal
   karyotype.

   v. Patients with hematologic malignancies featuring clonal expansion of eosinophils
   driven by genomic alterations of KIT or PDGFR (eg, HES or CEL) must have a diagnosis
   confirmed by a central independent pathologist and are eligible if they have
   progressed on or are intolerant of imatinib therapy. Patients with de novo imatinib
   resistant mutations, such as but not limited to KIT D816V or PDGFRA D842V, are
   eligible without prior imatinib therapy.

   c) Malignant glioma patients with genomic alterations potentially conferring
   sensitivity to DCC-2618 including, but not limited to, amplification and/or mutations
   of PDGFRA and/or KIT.

   i. Patients must not require use of enzyme-inducing antiepileptic drugs. ii. Patients
   that require steroids must be on a stable dose for 2 weeks prior to the first dose of
   study drug.

   d) Other solid tumor patients that have alterations in genes encoding kinases that are
   targets of DCC-2618. This includes KIT, PDGFR (A or B), TIE2, CSF1R, and VEGFR2.
   Patients must have received approved treatments known to provide clinical benefit
   prior to study entry.

   e) If signs or symptoms suggest CNS metastases, a brain MRI must be performed to
   confirm absence of CNS disease within 1 week prior to receiving study drug.

   2. Patients with known CNS metastases may participate provided that:

      1. they are stable (ie, without evidence of progression by magnetic resonance
      imaging [MRI]) for at least 4 weeks prior to the first dose study drug (patients
      with active disease may be eligible following discussion between the Investigator
      and the Sponsor),

      2. all neurologic symptoms have been stable for 2 weeks prior to the first dose of
      study drug,

      3. patients must not require use of enzyme-inducing antiepileptic drugs,

      4. patients that require steroids must be on a stable dose for 2 weeks prior to the
      first dose of study drug.

   3. Patients with solid tumors (with the exception of glial tumors and tumors that are
   anatomically inaccessible) must have an archival tumor biopsy sample as long as no
   anticancer therapy was administered since the sample was collected; otherwise, a
   current biopsy is required. In the case of glial tumors and anatomically inaccessible
   tumors, the most recent archival tissue is required.

   4. Male or female patients ≥18 years of age.

   5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.

   6. Female patients of childbearing potential must have a negative serum beta‑human
   chorionic gonadotropin (β-hCG) pregnancy test within 28 days prior to the start of
   study drug. For clinical sites in the UK, pregnancy testing must occur within 7 days
   prior to the start of study drug.

   7. Patients of reproductive potential must agree to follow the contraception requirements
   outlined in Section 6.8.11.

   8. The patient is capable of understanding and complying with the protocol and has signed
   the informed consent document. A signed informed consent form must be obtained before
   any study‑specific procedures are performed. Standard procedures performed as part of
   the practice of medicine prior to consent (eg, imaging, physical exam) can be used to
   determine eligibility if completed within 28 days prior to the initial dose of study
   drug.

   9. Patients with solid tumors must have at least 1 measurable lesion according to RECIST
   Version 1.1 (non-nodal lesions must be ≥1.0 cm in the long axis or ≥double the slice
   thickness in the long axis; nodal lesions must be ≥1.5 cm in the short axis) or
   Response Assessment in Neuro-Oncology Criteria (RANO).

   a) A non-brain lesion in a previously irradiated area is eligible to be considered as
   measurable disease as long as there is objective evidence of progression of the lesion
   before study enrollment.

10. Adequate organ function and bone marrow function as indicated by the following central
   laboratory screening assessments performed within 14 days prior to the first dose of
   study drug. Local laboratory values obtained after screening and prior to Cycle 1 Day
   1 dosing that do not meet the criteria below must be discussed with the Sponsor:

      1. Solid Tumor Patients: Bone Marrow Function: Absolute neutrophil count (ANC)
      ≥1500/μL; hemoglobin ≥9 g/dL; platelet count ≥75,000/μL.

      2. All Patients:

   i. Hepatic Function: Serum direct bilirubin ≤1.5 times the upper limit of normal (ULN)
   (≤3 × ULN if this elevation is solely due to ASM/MCL); aspartate transaminase
   (AST)/alanine transaminase (ALT), ≤3 × ULN (≤5 × ULN in the presence of hepatic
   metastases or if this elevation is solely due to ASM/MCL).

   ii. Renal Function: Serum creatinine ≤2.0 × ULN or creatinine clearance ≥50 mL/min
   based either on urine collection or Cockcroft Gault estimation.

   iii. Coagulation Profile: Prothrombin time (PT) - international normalized ratio
   (INR)/partial thromboplastin time (PTT) ≤1.5 × ULN. Patients on a stable, maintenance
   regimen of anticoagulant therapy for at least 30 days prior to study drug
   administration may have PT/INR measurements >1.5 × ULN if, in the opinion of the
   Investigator, the patient is suitable for the study. An adequate rationale must be
   provided to the Sponsor prior to enrollment.

   c) SM patients with one or more inadequate organ function laboratory value may be
   eligible if both the Investigator and Sponsor deem it to be disease-related and the
   abnormality qualifies as a C-Finding (see Appendix 10.5).

11. Resolution of all toxicities from prior therapy to ≤Grade 1 (or baseline) within 1
   week prior to the first dose of study drug (excluding alopecia and ≤Grade 3 clinically
   asymptomatic lipase, amylase, and creatine phosphokinase laboratory abnormalities).

Exclusion Criteria (Escalation and Expansion Phases)

Patients meeting any of the following criteria will be excluded from the study:

   1. GIST patients with wild type or unknown KIT or PDGFRA status.

   2. Patients with SM or other hematologic malignancies will be excluded if the following
   apply:

      1. SM patients with wild type KIT mutational status.

      2. SM patients with neutropenia accompanied by fever or infection, or
      thrombocytopenia associated with clinically significant bleeding.

         - Patients with an infection that is well controlled with antibiotics are
         eligible if there is an immediate need for treatment

      3. SM-AHN patients diagnosed with:

   i. SM with MDS (SM-MDS) who require treatment for MDS. ii. Patients requiring
   immediate treatment for AHN. d) Patients with leukemias, with the exception of MCL and
   CEL, that have progressed after imatinib.

   e) Eosinophilic myeloproliferative neoplasm patients: i. Lacking a mutation that is a
   known target of DCC-2618. This includes, but is not limited to, fusions/mutations of
   FGFR1, JAK2, and ABL.

   3. Has a known additional malignancy that is progressing or required active treatment
   within 3 years of the first dose of study treatment. Exceptions include basal cell
   carcinoma of the skin, squamous cell carcinoma of the skin that has undergone
   potentially curative therapy, or other in situ cancers.

   4. Treatment with anticancer therapy, including investigational therapy, within 2 weeks
   prior to the administration of study drug, with the exception of hydroxyurea that is
   allowed to control white blood cell count. For prior therapies with a half-life longer
   than 3 days, the interval must be at least 28 days prior to the first administration
   of study drug.

   5. New York Heart Association class III and IV heart disease, active ischemia or any
   other uncontrolled cardiac condition such as angina pectoris, clinically significant
   cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart
   failure.

   6. Arterial thrombotic or embolic events such as cerebrovascular accident (including
   ischemic attacks) or hemoptysis within 6 months before start of study drug.

   7. Venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg,
   pulmonary embolism) within the 3 months before start of study drug. Patients with
   venous thrombotic events ≥3 months before start of study drug on stable
   anticoagulation therapy are eligible.

   8. Baseline prolongation of the rate-corrected QT interval based on repeated
   demonstration of QT interval corrected by Fridericia's formula (QTcF) >450 ms in males
   or >470 ms in females or history of long QT interval corrected (QTc) syndrome.

   9. LVEF <50% or below the lower limit of normal (whichever is higher).

10. Major surgery within 4 weeks of the first dose of study drug; following major
   surgeries >4 weeks prior to the first dose of study drug, all surgical wounds must be
   healed and free of infection or dehiscence.

11. Any other clinically significant comorbidities, such as uncontrolled pulmonary
   disease, active infection, or any other condition, which in the judgment of the
   Investigator, could compromise compliance with the protocol, interfere with the
   interpretation of study results, or predispose the patient to safety risks.

12. Malabsorption syndrome or other illness that could affect oral absorption.

13. Known human immunodeficiency virus or active hepatitis C infection only if the patient
   is taking medications that are described in Section 5.8.2.2, active hepatitis B, or
   active hepatitis C infection.

14. If female, the patient is pregnant or lactating.

15. Known allergy or hypersensitivity to any component of the investigational drug
   product.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Justin Abuel
650-723-1367
Recruiting

A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies

The purpose of this Phase 1 study is to determine the safety, tolerability, maximum tolerated dose, and (preliminary) effectiveness of oral DCC-2618 in patients with advanced malignancies. The study will also determine the pharmacokinetic and pharmacodynamics profile of oral DCC-2618. The study will consist of an Escalation Phase in patients with advanced malignancies (to test safety and to determine the maximum tolerated dose of the study drug) followed by an Expansion Phase in select tumors (to further test the safety and tolerability and to obtain preliminary evidence of efficacy of the study drug). At Stanford we will be taking part in the expansion phase, for patients with GIST.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Deciphera Pharmaceuticals LLC

Intervention(s):

  • Drug: DCC-2618

Phase:

Phase 1

Eligibility


Inclusion Criteria (Escalation and Expansion Phases)

Patients must meet the following criteria to be eligible to enroll in the study:

   1. Patients must have histologically confirmed solid tumors or hematologic malignancies.
   Eligible patients include the following:

   a) GIST patients must have a KIT and PDGFRA mutation and must have progressed on or
   had an intolerability to at least 1 line of systemic anticancer therapy: i. Patients
   with a pre-existing resistance mutation to an approved line of therapy are eligible.
   For example, imatinib resistant mutations including KIT Exon 17 and PDGFRA D842V.

   b) SM patients must have a confirmed diagnosis (confirmed by a central independent
   pathologist) of advanced SM according to 2016 World Health Organization (WHO) criteria
   for SM and must have documented KIT mutant disease. SM patients must also have a
   normal karyotype.

   Advanced SM includes: ASM, SM-AHN, wherein the AHN does not require immediate
   alternative therapy, such as acute myeloid leukemia. AHNs that are eligible include:
   low grade myelodysplastic syndrome (MDS) with a high SM burden who require treatment
   for SM only, myeloproliferative neoplasms (MPNs), MDS/MPN, and HES/CEL], and MCL i.
   Patients with advanced SM must present with at least 1 eligible C-Finding (organ
   damage) as outlined in Table 3 of the 2013 International Working
   Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European
   Competence Network on Mastocytosis (ECNM) consensus response criteria (Appendix 10.5);
   please see below for MCL exception) (#iii).

   ii. Patients with imatinib-sensitive KIT mutations must have progressed on or were
   intolerant to a tryosine kinase inhibitor.

   iii. Patients with histopathologically-confirmed MCL without a C-finding are eligible.

   iv. Patients with symptomatic SSM are eligible. By definition, SSM patients must have
   at least 2 B-findings, and clinically significant symptom burden (eg, flushing,
   diarrhea, etc.) despite maximal treatment with approved agents to treat mediator
   symptoms, such as antihistamines and cromolyn sodium. Patients must have a normal
   karyotype.

   v. Patients with hematologic malignancies featuring clonal expansion of eosinophils
   driven by genomic alterations of KIT or PDGFR (eg, HES or CEL) must have a diagnosis
   confirmed by a central independent pathologist and are eligible if they have
   progressed on or are intolerant of imatinib therapy. Patients with de novo imatinib
   resistant mutations, such as but not limited to KIT D816V or PDGFRA D842V, are
   eligible without prior imatinib therapy.

   c) Malignant glioma patients with genomic alterations potentially conferring
   sensitivity to DCC-2618 including, but not limited to, amplification and/or mutations
   of PDGFRA and/or KIT.

   i. Patients must not require use of enzyme-inducing antiepileptic drugs. ii. Patients
   that require steroids must be on a stable dose for 2 weeks prior to the first dose of
   study drug.

   d) Other solid tumor patients that have alterations in genes encoding kinases that are
   targets of DCC-2618. This includes KIT, PDGFR (A or B), TIE2, CSF1R, and VEGFR2.
   Patients must have received approved treatments known to provide clinical benefit
   prior to study entry.

   e) If signs or symptoms suggest CNS metastases, a brain MRI must be performed to
   confirm absence of CNS disease within 1 week prior to receiving study drug.

   2. Patients with known CNS metastases may participate provided that:

      1. they are stable (ie, without evidence of progression by magnetic resonance
      imaging [MRI]) for at least 4 weeks prior to the first dose study drug (patients
      with active disease may be eligible following discussion between the Investigator
      and the Sponsor),

      2. all neurologic symptoms have been stable for 2 weeks prior to the first dose of
      study drug,

      3. patients must not require use of enzyme-inducing antiepileptic drugs,

      4. patients that require steroids must be on a stable dose for 2 weeks prior to the
      first dose of study drug.

   3. Patients with solid tumors (with the exception of glial tumors and tumors that are
   anatomically inaccessible) must have an archival tumor biopsy sample as long as no
   anticancer therapy was administered since the sample was collected; otherwise, a
   current biopsy is required. In the case of glial tumors and anatomically inaccessible
   tumors, the most recent archival tissue is required.

   4. Male or female patients ≥18 years of age.

   5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.

   6. Female patients of childbearing potential must have a negative serum beta‑human
   chorionic gonadotropin (β-hCG) pregnancy test within 28 days prior to the start of
   study drug. For clinical sites in the UK, pregnancy testing must occur within 7 days
   prior to the start of study drug.

   7. Patients of reproductive potential must agree to follow the contraception requirements
   outlined in Section 6.8.11.

   8. The patient is capable of understanding and complying with the protocol and has signed
   the informed consent document. A signed informed consent form must be obtained before
   any study‑specific procedures are performed. Standard procedures performed as part of
   the practice of medicine prior to consent (eg, imaging, physical exam) can be used to
   determine eligibility if completed within 28 days prior to the initial dose of study
   drug.

   9. Patients with solid tumors must have at least 1 measurable lesion according to RECIST
   Version 1.1 (non-nodal lesions must be ≥1.0 cm in the long axis or ≥double the slice
   thickness in the long axis; nodal lesions must be ≥1.5 cm in the short axis) or
   Response Assessment in Neuro-Oncology Criteria (RANO).

   a) A non-brain lesion in a previously irradiated area is eligible to be considered as
   measurable disease as long as there is objective evidence of progression of the lesion
   before study enrollment.

10. Adequate organ function and bone marrow function as indicated by the following central
   laboratory screening assessments performed within 14 days prior to the first dose of
   study drug. Local laboratory values obtained after screening and prior to Cycle 1 Day
   1 dosing that do not meet the criteria below must be discussed with the Sponsor:

      1. Solid Tumor Patients: Bone Marrow Function: Absolute neutrophil count (ANC)
      ≥1500/μL; hemoglobin ≥9 g/dL; platelet count ≥75,000/μL.

      2. All Patients:

   i. Hepatic Function: Serum direct bilirubin ≤1.5 times the upper limit of normal (ULN)
   (≤3 × ULN if this elevation is solely due to ASM/MCL); aspartate transaminase
   (AST)/alanine transaminase (ALT), ≤3 × ULN (≤5 × ULN in the presence of hepatic
   metastases or if this elevation is solely due to ASM/MCL).

   ii. Renal Function: Serum creatinine ≤2.0 × ULN or creatinine clearance ≥50 mL/min
   based either on urine collection or Cockcroft Gault estimation.

   iii. Coagulation Profile: Prothrombin time (PT) - international normalized ratio
   (INR)/partial thromboplastin time (PTT) ≤1.5 × ULN. Patients on a stable, maintenance
   regimen of anticoagulant therapy for at least 30 days prior to study drug
   administration may have PT/INR measurements >1.5 × ULN if, in the opinion of the
   Investigator, the patient is suitable for the study. An adequate rationale must be
   provided to the Sponsor prior to enrollment.

   c) SM patients with one or more inadequate organ function laboratory value may be
   eligible if both the Investigator and Sponsor deem it to be disease-related and the
   abnormality qualifies as a C-Finding (see Appendix 10.5).

11. Resolution of all toxicities from prior therapy to ≤Grade 1 (or baseline) within 1
   week prior to the first dose of study drug (excluding alopecia and ≤Grade 3 clinically
   asymptomatic lipase, amylase, and creatine phosphokinase laboratory abnormalities).

Exclusion Criteria (Escalation and Expansion Phases)

Patients meeting any of the following criteria will be excluded from the study:

   1. GIST patients with wild type or unknown KIT or PDGFRA status.

   2. Patients with SM or other hematologic malignancies will be excluded if the following
   apply:

      1. SM patients with wild type KIT mutational status.

      2. SM patients with neutropenia accompanied by fever or infection, or
      thrombocytopenia associated with clinically significant bleeding.

         - Patients with an infection that is well controlled with antibiotics are
         eligible if there is an immediate need for treatment

      3. SM-AHN patients diagnosed with:

   i. SM with MDS (SM-MDS) who require treatment for MDS. ii. Patients requiring
   immediate treatment for AHN. d) Patients with leukemias, with the exception of MCL and
   CEL, that have progressed after imatinib.

   e) Eosinophilic myeloproliferative neoplasm patients: i. Lacking a mutation that is a
   known target of DCC-2618. This includes, but is not limited to, fusions/mutations of
   FGFR1, JAK2, and ABL.

   3. Has a known additional malignancy that is progressing or required active treatment
   within 3 years of the first dose of study treatment. Exceptions include basal cell
   carcinoma of the skin, squamous cell carcinoma of the skin that has undergone
   potentially curative therapy, or other in situ cancers.

   4. Treatment with anticancer therapy, including investigational therapy, within 2 weeks
   prior to the administration of study drug, with the exception of hydroxyurea that is
   allowed to control white blood cell count. For prior therapies with a half-life longer
   than 3 days, the interval must be at least 28 days prior to the first administration
   of study drug.

   5. New York Heart Association class III and IV heart disease, active ischemia or any
   other uncontrolled cardiac condition such as angina pectoris, clinically significant
   cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart
   failure.

   6. Arterial thrombotic or embolic events such as cerebrovascular accident (including
   ischemic attacks) or hemoptysis within 6 months before start of study drug.

   7. Venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg,
   pulmonary embolism) within the 3 months before start of study drug. Patients with
   venous thrombotic events ≥3 months before start of study drug on stable
   anticoagulation therapy are eligible.

   8. Baseline prolongation of the rate-corrected QT interval based on repeated
   demonstration of QT interval corrected by Fridericia's formula (QTcF) >450 ms in males
   or >470 ms in females or history of long QT interval corrected (QTc) syndrome.

   9. LVEF <50% or below the lower limit of normal (whichever is higher).

10. Major surgery within 4 weeks of the first dose of study drug; following major
   surgeries >4 weeks prior to the first dose of study drug, all surgical wounds must be
   healed and free of infection or dehiscence.

11. Any other clinically significant comorbidities, such as uncontrolled pulmonary
   disease, active infection, or any other condition, which in the judgment of the
   Investigator, could compromise compliance with the protocol, interfere with the
   interpretation of study results, or predispose the patient to safety risks.

12. Malabsorption syndrome or other illness that could affect oral absorption.

13. Known human immunodeficiency virus or active hepatitis C infection only if the patient
   is taking medications that are described in Section 5.8.2.2, active hepatitis B, or
   active hepatitis C infection.

14. If female, the patient is pregnant or lactating.

15. Known allergy or hypersensitivity to any component of the investigational drug
   product.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Justin Abuel
650-723-1367
Recruiting

A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies

The purpose of this Phase 1 study is to determine the safety, tolerability, maximum tolerated dose, and (preliminary) effectiveness of oral DCC-2618 in patients with advanced malignancies. The study will also determine the pharmacokinetic and pharmacodynamics profile of oral DCC-2618. The study will consist of an Escalation Phase in patients with advanced malignancies (to test safety and to determine the maximum tolerated dose of the study drug) followed by an Expansion Phase in select tumors (to further test the safety and tolerability and to obtain preliminary evidence of efficacy of the study drug). At Stanford we will be taking part in the expansion phase, for patients with GIST.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Deciphera Pharmaceuticals LLC

Intervention(s):

  • Drug: DCC-2618

Phase:

Phase 1

Eligibility


Inclusion Criteria (Escalation and Expansion Phases)

Patients must meet the following criteria to be eligible to enroll in the study:

   1. Patients must have histologically confirmed solid tumors or hematologic malignancies.
   Eligible patients include the following:

   a) GIST patients must have a KIT and PDGFRA mutation and must have progressed on or
   had an intolerability to at least 1 line of systemic anticancer therapy: i. Patients
   with a pre-existing resistance mutation to an approved line of therapy are eligible.
   For example, imatinib resistant mutations including KIT Exon 17 and PDGFRA D842V.

   b) SM patients must have a confirmed diagnosis (confirmed by a central independent
   pathologist) of advanced SM according to 2016 World Health Organization (WHO) criteria
   for SM and must have documented KIT mutant disease. SM patients must also have a
   normal karyotype.

   Advanced SM includes: ASM, SM-AHN, wherein the AHN does not require immediate
   alternative therapy, such as acute myeloid leukemia. AHNs that are eligible include:
   low grade myelodysplastic syndrome (MDS) with a high SM burden who require treatment
   for SM only, myeloproliferative neoplasms (MPNs), MDS/MPN, and HES/CEL], and MCL i.
   Patients with advanced SM must present with at least 1 eligible C-Finding (organ
   damage) as outlined in Table 3 of the 2013 International Working
   Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European
   Competence Network on Mastocytosis (ECNM) consensus response criteria (Appendix 10.5);
   please see below for MCL exception) (#iii).

   ii. Patients with imatinib-sensitive KIT mutations must have progressed on or were
   intolerant to a tryosine kinase inhibitor.

   iii. Patients with histopathologically-confirmed MCL without a C-finding are eligible.

   iv. Patients with symptomatic SSM are eligible. By definition, SSM patients must have
   at least 2 B-findings, and clinically significant symptom burden (eg, flushing,
   diarrhea, etc.) despite maximal treatment with approved agents to treat mediator
   symptoms, such as antihistamines and cromolyn sodium. Patients must have a normal
   karyotype.

   v. Patients with hematologic malignancies featuring clonal expansion of eosinophils
   driven by genomic alterations of KIT or PDGFR (eg, HES or CEL) must have a diagnosis
   confirmed by a central independent pathologist and are eligible if they have
   progressed on or are intolerant of imatinib therapy. Patients with de novo imatinib
   resistant mutations, such as but not limited to KIT D816V or PDGFRA D842V, are
   eligible without prior imatinib therapy.

   c) Malignant glioma patients with genomic alterations potentially conferring
   sensitivity to DCC-2618 including, but not limited to, amplification and/or mutations
   of PDGFRA and/or KIT.

   i. Patients must not require use of enzyme-inducing antiepileptic drugs. ii. Patients
   that require steroids must be on a stable dose for 2 weeks prior to the first dose of
   study drug.

   d) Other solid tumor patients that have alterations in genes encoding kinases that are
   targets of DCC-2618. This includes KIT, PDGFR (A or B), TIE2, CSF1R, and VEGFR2.
   Patients must have received approved treatments known to provide clinical benefit
   prior to study entry.

   e) If signs or symptoms suggest CNS metastases, a brain MRI must be performed to
   confirm absence of CNS disease within 1 week prior to receiving study drug.

   2. Patients with known CNS metastases may participate provided that:

      1. they are stable (ie, without evidence of progression by magnetic resonance
      imaging [MRI]) for at least 4 weeks prior to the first dose study drug (patients
      with active disease may be eligible following discussion between the Investigator
      and the Sponsor),

      2. all neurologic symptoms have been stable for 2 weeks prior to the first dose of
      study drug,

      3. patients must not require use of enzyme-inducing antiepileptic drugs,

      4. patients that require steroids must be on a stable dose for 2 weeks prior to the
      first dose of study drug.

   3. Patients with solid tumors (with the exception of glial tumors and tumors that are
   anatomically inaccessible) must have an archival tumor biopsy sample as long as no
   anticancer therapy was administered since the sample was collected; otherwise, a
   current biopsy is required. In the case of glial tumors and anatomically inaccessible
   tumors, the most recent archival tissue is required.

   4. Male or female patients ≥18 years of age.

   5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.

   6. Female patients of childbearing potential must have a negative serum beta‑human
   chorionic gonadotropin (β-hCG) pregnancy test within 28 days prior to the start of
   study drug. For clinical sites in the UK, pregnancy testing must occur within 7 days
   prior to the start of study drug.

   7. Patients of reproductive potential must agree to follow the contraception requirements
   outlined in Section 6.8.11.

   8. The patient is capable of understanding and complying with the protocol and has signed
   the informed consent document. A signed informed consent form must be obtained before
   any study‑specific procedures are performed. Standard procedures performed as part of
   the practice of medicine prior to consent (eg, imaging, physical exam) can be used to
   determine eligibility if completed within 28 days prior to the initial dose of study
   drug.

   9. Patients with solid tumors must have at least 1 measurable lesion according to RECIST
   Version 1.1 (non-nodal lesions must be ≥1.0 cm in the long axis or ≥double the slice
   thickness in the long axis; nodal lesions must be ≥1.5 cm in the short axis) or
   Response Assessment in Neuro-Oncology Criteria (RANO).

   a) A non-brain lesion in a previously irradiated area is eligible to be considered as
   measurable disease as long as there is objective evidence of progression of the lesion
   before study enrollment.

10. Adequate organ function and bone marrow function as indicated by the following central
   laboratory screening assessments performed within 14 days prior to the first dose of
   study drug. Local laboratory values obtained after screening and prior to Cycle 1 Day
   1 dosing that do not meet the criteria below must be discussed with the Sponsor:

      1. Solid Tumor Patients: Bone Marrow Function: Absolute neutrophil count (ANC)
      ≥1500/μL; hemoglobin ≥9 g/dL; platelet count ≥75,000/μL.

      2. All Patients:

   i. Hepatic Function: Serum direct bilirubin ≤1.5 times the upper limit of normal (ULN)
   (≤3 × ULN if this elevation is solely due to ASM/MCL); aspartate transaminase
   (AST)/alanine transaminase (ALT), ≤3 × ULN (≤5 × ULN in the presence of hepatic
   metastases or if this elevation is solely due to ASM/MCL).

   ii. Renal Function: Serum creatinine ≤2.0 × ULN or creatinine clearance ≥50 mL/min
   based either on urine collection or Cockcroft Gault estimation.

   iii. Coagulation Profile: Prothrombin time (PT) - international normalized ratio
   (INR)/partial thromboplastin time (PTT) ≤1.5 × ULN. Patients on a stable, maintenance
   regimen of anticoagulant therapy for at least 30 days prior to study drug
   administration may have PT/INR measurements >1.5 × ULN if, in the opinion of the
   Investigator, the patient is suitable for the study. An adequate rationale must be
   provided to the Sponsor prior to enrollment.

   c) SM patients with one or more inadequate organ function laboratory value may be
   eligible if both the Investigator and Sponsor deem it to be disease-related and the
   abnormality qualifies as a C-Finding (see Appendix 10.5).

11. Resolution of all toxicities from prior therapy to ≤Grade 1 (or baseline) within 1
   week prior to the first dose of study drug (excluding alopecia and ≤Grade 3 clinically
   asymptomatic lipase, amylase, and creatine phosphokinase laboratory abnormalities).

Exclusion Criteria (Escalation and Expansion Phases)

Patients meeting any of the following criteria will be excluded from the study:

   1. GIST patients with wild type or unknown KIT or PDGFRA status.

   2. Patients with SM or other hematologic malignancies will be excluded if the following
   apply:

      1. SM patients with wild type KIT mutational status.

      2. SM patients with neutropenia accompanied by fever or infection, or
      thrombocytopenia associated with clinically significant bleeding.

         - Patients with an infection that is well controlled with antibiotics are
         eligible if there is an immediate need for treatment

      3. SM-AHN patients diagnosed with:

   i. SM with MDS (SM-MDS) who require treatment for MDS. ii. Patients requiring
   immediate treatment for AHN. d) Patients with leukemias, with the exception of MCL and
   CEL, that have progressed after imatinib.

   e) Eosinophilic myeloproliferative neoplasm patients: i. Lacking a mutation that is a
   known target of DCC-2618. This includes, but is not limited to, fusions/mutations of
   FGFR1, JAK2, and ABL.

   3. Has a known additional malignancy that is progressing or required active treatment
   within 3 years of the first dose of study treatment. Exceptions include basal cell
   carcinoma of the skin, squamous cell carcinoma of the skin that has undergone
   potentially curative therapy, or other in situ cancers.

   4. Treatment with anticancer therapy, including investigational therapy, within 2 weeks
   prior to the administration of study drug, with the exception of hydroxyurea that is
   allowed to control white blood cell count. For prior therapies with a half-life longer
   than 3 days, the interval must be at least 28 days prior to the first administration
   of study drug.

   5. New York Heart Association class III and IV heart disease, active ischemia or any
   other uncontrolled cardiac condition such as angina pectoris, clinically significant
   cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart
   failure.

   6. Arterial thrombotic or embolic events such as cerebrovascular accident (including
   ischemic attacks) or hemoptysis within 6 months before start of study drug.

   7. Venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg,
   pulmonary embolism) within the 3 months before start of study drug. Patients with
   venous thrombotic events ≥3 months before start of study drug on stable
   anticoagulation therapy are eligible.

   8. Baseline prolongation of the rate-corrected QT interval based on repeated
   demonstration of QT interval corrected by Fridericia's formula (QTcF) >450 ms in males
   or >470 ms in females or history of long QT interval corrected (QTc) syndrome.

   9. LVEF <50% or below the lower limit of normal (whichever is higher).

10. Major surgery within 4 weeks of the first dose of study drug; following major
   surgeries >4 weeks prior to the first dose of study drug, all surgical wounds must be
   healed and free of infection or dehiscence.

11. Any other clinically significant comorbidities, such as uncontrolled pulmonary
   disease, active infection, or any other condition, which in the judgment of the
   Investigator, could compromise compliance with the protocol, interfere with the
   interpretation of study results, or predispose the patient to safety risks.

12. Malabsorption syndrome or other illness that could affect oral absorption.

13. Known human immunodeficiency virus or active hepatitis C infection only if the patient
   is taking medications that are described in Section 5.8.2.2, active hepatitis B, or
   active hepatitis C infection.

14. If female, the patient is pregnant or lactating.

15. Known allergy or hypersensitivity to any component of the investigational drug
   product.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Justin Abuel
650-723-1367
Recruiting

A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies

The purpose of this Phase 1 study is to determine the safety, tolerability, maximum tolerated dose, and (preliminary) effectiveness of oral DCC-2618 in patients with advanced malignancies. The study will also determine the pharmacokinetic and pharmacodynamics profile of oral DCC-2618. The study will consist of an Escalation Phase in patients with advanced malignancies (to test safety and to determine the maximum tolerated dose of the study drug) followed by an Expansion Phase in select tumors (to further test the safety and tolerability and to obtain preliminary evidence of efficacy of the study drug). At Stanford we will be taking part in the expansion phase, for patients with GIST.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Deciphera Pharmaceuticals LLC

Intervention(s):

  • Drug: DCC-2618

Phase:

Phase 1

Eligibility


Inclusion Criteria (Escalation and Expansion Phases)

Patients must meet the following criteria to be eligible to enroll in the study:

   1. Patients must have histologically confirmed solid tumors or hematologic malignancies.
   Eligible patients include the following:

   a) GIST patients must have a KIT and PDGFRA mutation and must have progressed on or
   had an intolerability to at least 1 line of systemic anticancer therapy: i. Patients
   with a pre-existing resistance mutation to an approved line of therapy are eligible.
   For example, imatinib resistant mutations including KIT Exon 17 and PDGFRA D842V.

   b) SM patients must have a confirmed diagnosis (confirmed by a central independent
   pathologist) of advanced SM according to 2016 World Health Organization (WHO) criteria
   for SM and must have documented KIT mutant disease. SM patients must also have a
   normal karyotype.

   Advanced SM includes: ASM, SM-AHN, wherein the AHN does not require immediate
   alternative therapy, such as acute myeloid leukemia. AHNs that are eligible include:
   low grade myelodysplastic syndrome (MDS) with a high SM burden who require treatment
   for SM only, myeloproliferative neoplasms (MPNs), MDS/MPN, and HES/CEL], and MCL i.
   Patients with advanced SM must present with at least 1 eligible C-Finding (organ
   damage) as outlined in Table 3 of the 2013 International Working
   Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European
   Competence Network on Mastocytosis (ECNM) consensus response criteria (Appendix 10.5);
   please see below for MCL exception) (#iii).

   ii. Patients with imatinib-sensitive KIT mutations must have progressed on or were
   intolerant to a tryosine kinase inhibitor.

   iii. Patients with histopathologically-confirmed MCL without a C-finding are eligible.

   iv. Patients with symptomatic SSM are eligible. By definition, SSM patients must have
   at least 2 B-findings, and clinically significant symptom burden (eg, flushing,
   diarrhea, etc.) despite maximal treatment with approved agents to treat mediator
   symptoms, such as antihistamines and cromolyn sodium. Patients must have a normal
   karyotype.

   v. Patients with hematologic malignancies featuring clonal expansion of eosinophils
   driven by genomic alterations of KIT or PDGFR (eg, HES or CEL) must have a diagnosis
   confirmed by a central independent pathologist and are eligible if they have
   progressed on or are intolerant of imatinib therapy. Patients with de novo imatinib
   resistant mutations, such as but not limited to KIT D816V or PDGFRA D842V, are
   eligible without prior imatinib therapy.

   c) Malignant glioma patients with genomic alterations potentially conferring
   sensitivity to DCC-2618 including, but not limited to, amplification and/or mutations
   of PDGFRA and/or KIT.

   i. Patients must not require use of enzyme-inducing antiepileptic drugs. ii. Patients
   that require steroids must be on a stable dose for 2 weeks prior to the first dose of
   study drug.

   d) Other solid tumor patients that have alterations in genes encoding kinases that are
   targets of DCC-2618. This includes KIT, PDGFR (A or B), TIE2, CSF1R, and VEGFR2.
   Patients must have received approved treatments known to provide clinical benefit
   prior to study entry.

   e) If signs or symptoms suggest CNS metastases, a brain MRI must be performed to
   confirm absence of CNS disease within 1 week prior to receiving study drug.

   2. Patients with known CNS metastases may participate provided that:

      1. they are stable (ie, without evidence of progression by magnetic resonance
      imaging [MRI]) for at least 4 weeks prior to the first dose study drug (patients
      with active disease may be eligible following discussion between the Investigator
      and the Sponsor),

      2. all neurologic symptoms have been stable for 2 weeks prior to the first dose of
      study drug,

      3. patients must not require use of enzyme-inducing antiepileptic drugs,

      4. patients that require steroids must be on a stable dose for 2 weeks prior to the
      first dose of study drug.

   3. Patients with solid tumors (with the exception of glial tumors and tumors that are
   anatomically inaccessible) must have an archival tumor biopsy sample as long as no
   anticancer therapy was administered since the sample was collected; otherwise, a
   current biopsy is required. In the case of glial tumors and anatomically inaccessible
   tumors, the most recent archival tissue is required.

   4. Male or female patients ≥18 years of age.

   5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.

   6. Female patients of childbearing potential must have a negative serum beta‑human
   chorionic gonadotropin (β-hCG) pregnancy test within 28 days prior to the start of
   study drug. For clinical sites in the UK, pregnancy testing must occur within 7 days
   prior to the start of study drug.

   7. Patients of reproductive potential must agree to follow the contraception requirements
   outlined in Section 6.8.11.

   8. The patient is capable of understanding and complying with the protocol and has signed
   the informed consent document. A signed informed consent form must be obtained before
   any study‑specific procedures are performed. Standard procedures performed as part of
   the practice of medicine prior to consent (eg, imaging, physical exam) can be used to
   determine eligibility if completed within 28 days prior to the initial dose of study
   drug.

   9. Patients with solid tumors must have at least 1 measurable lesion according to RECIST
   Version 1.1 (non-nodal lesions must be ≥1.0 cm in the long axis or ≥double the slice
   thickness in the long axis; nodal lesions must be ≥1.5 cm in the short axis) or
   Response Assessment in Neuro-Oncology Criteria (RANO).

   a) A non-brain lesion in a previously irradiated area is eligible to be considered as
   measurable disease as long as there is objective evidence of progression of the lesion
   before study enrollment.

10. Adequate organ function and bone marrow function as indicated by the following central
   laboratory screening assessments performed within 14 days prior to the first dose of
   study drug. Local laboratory values obtained after screening and prior to Cycle 1 Day
   1 dosing that do not meet the criteria below must be discussed with the Sponsor:

      1. Solid Tumor Patients: Bone Marrow Function: Absolute neutrophil count (ANC)
      ≥1500/μL; hemoglobin ≥9 g/dL; platelet count ≥75,000/μL.

      2. All Patients:

   i. Hepatic Function: Serum direct bilirubin ≤1.5 times the upper limit of normal (ULN)
   (≤3 × ULN if this elevation is solely due to ASM/MCL); aspartate transaminase
   (AST)/alanine transaminase (ALT), ≤3 × ULN (≤5 × ULN in the presence of hepatic
   metastases or if this elevation is solely due to ASM/MCL).

   ii. Renal Function: Serum creatinine ≤2.0 × ULN or creatinine clearance ≥50 mL/min
   based either on urine collection or Cockcroft Gault estimation.

   iii. Coagulation Profile: Prothrombin time (PT) - international normalized ratio
   (INR)/partial thromboplastin time (PTT) ≤1.5 × ULN. Patients on a stable, maintenance
   regimen of anticoagulant therapy for at least 30 days prior to study drug
   administration may have PT/INR measurements >1.5 × ULN if, in the opinion of the
   Investigator, the patient is suitable for the study. An adequate rationale must be
   provided to the Sponsor prior to enrollment.

   c) SM patients with one or more inadequate organ function laboratory value may be
   eligible if both the Investigator and Sponsor deem it to be disease-related and the
   abnormality qualifies as a C-Finding (see Appendix 10.5).

11. Resolution of all toxicities from prior therapy to ≤Grade 1 (or baseline) within 1
   week prior to the first dose of study drug (excluding alopecia and ≤Grade 3 clinically
   asymptomatic lipase, amylase, and creatine phosphokinase laboratory abnormalities).

Exclusion Criteria (Escalation and Expansion Phases)

Patients meeting any of the following criteria will be excluded from the study:

   1. GIST patients with wild type or unknown KIT or PDGFRA status.

   2. Patients with SM or other hematologic malignancies will be excluded if the following
   apply:

      1. SM patients with wild type KIT mutational status.

      2. SM patients with neutropenia accompanied by fever or infection, or
      thrombocytopenia associated with clinically significant bleeding.

         - Patients with an infection that is well controlled with antibiotics are
         eligible if there is an immediate need for treatment

      3. SM-AHN patients diagnosed with:

   i. SM with MDS (SM-MDS) who require treatment for MDS. ii. Patients requiring
   immediate treatment for AHN. d) Patients with leukemias, with the exception of MCL and
   CEL, that have progressed after imatinib.

   e) Eosinophilic myeloproliferative neoplasm patients: i. Lacking a mutation that is a
   known target of DCC-2618. This includes, but is not limited to, fusions/mutations of
   FGFR1, JAK2, and ABL.

   3. Has a known additional malignancy that is progressing or required active treatment
   within 3 years of the first dose of study treatment. Exceptions include basal cell
   carcinoma of the skin, squamous cell carcinoma of the skin that has undergone
   potentially curative therapy, or other in situ cancers.

   4. Treatment with anticancer therapy, including investigational therapy, within 2 weeks
   prior to the administration of study drug, with the exception of hydroxyurea that is
   allowed to control white blood cell count. For prior therapies with a half-life longer
   than 3 days, the interval must be at least 28 days prior to the first administration
   of study drug.

   5. New York Heart Association class III and IV heart disease, active ischemia or any
   other uncontrolled cardiac condition such as angina pectoris, clinically significant
   cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart
   failure.

   6. Arterial thrombotic or embolic events such as cerebrovascular accident (including
   ischemic attacks) or hemoptysis within 6 months before start of study drug.

   7. Venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg,
   pulmonary embolism) within the 3 months before start of study drug. Patients with
   venous thrombotic events ≥3 months before start of study drug on stable
   anticoagulation therapy are eligible.

   8. Baseline prolongation of the rate-corrected QT interval based on repeated
   demonstration of QT interval corrected by Fridericia's formula (QTcF) >450 ms in males
   or >470 ms in females or history of long QT interval corrected (QTc) syndrome.

   9. LVEF <50% or below the lower limit of normal (whichever is higher).

10. Major surgery within 4 weeks of the first dose of study drug; following major
   surgeries >4 weeks prior to the first dose of study drug, all surgical wounds must be
   healed and free of infection or dehiscence.

11. Any other clinically significant comorbidities, such as uncontrolled pulmonary
   disease, active infection, or any other condition, which in the judgment of the
   Investigator, could compromise compliance with the protocol, interfere with the
   interpretation of study results, or predispose the patient to safety risks.

12. Malabsorption syndrome or other illness that could affect oral absorption.

13. Known human immunodeficiency virus or active hepatitis C infection only if the patient
   is taking medications that are described in Section 5.8.2.2, active hepatitis B, or
   active hepatitis C infection.

14. If female, the patient is pregnant or lactating.

15. Known allergy or hypersensitivity to any component of the investigational drug
   product.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Justin Abuel
650-723-1367
Recruiting

A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies

The purpose of this Phase 1 study is to determine the safety, tolerability, maximum tolerated dose, and (preliminary) effectiveness of oral DCC-2618 in patients with advanced malignancies. The study will also determine the pharmacokinetic and pharmacodynamics profile of oral DCC-2618. The study will consist of an Escalation Phase in patients with advanced malignancies (to test safety and to determine the maximum tolerated dose of the study drug) followed by an Expansion Phase in select tumors (to further test the safety and tolerability and to obtain preliminary evidence of efficacy of the study drug). At Stanford we will be taking part in the expansion phase, for patients with GIST.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Deciphera Pharmaceuticals LLC

Intervention(s):

  • Drug: DCC-2618

Phase:

Phase 1

Eligibility


Inclusion Criteria (Escalation and Expansion Phases)

Patients must meet the following criteria to be eligible to enroll in the study:

   1. Patients must have histologically confirmed solid tumors or hematologic malignancies.
   Eligible patients include the following:

   a) GIST patients must have a KIT and PDGFRA mutation and must have progressed on or
   had an intolerability to at least 1 line of systemic anticancer therapy: i. Patients
   with a pre-existing resistance mutation to an approved line of therapy are eligible.
   For example, imatinib resistant mutations including KIT Exon 17 and PDGFRA D842V.

   b) SM patients must have a confirmed diagnosis (confirmed by a central independent
   pathologist) of advanced SM according to 2016 World Health Organization (WHO) criteria
   for SM and must have documented KIT mutant disease. SM patients must also have a
   normal karyotype.

   Advanced SM includes: ASM, SM-AHN, wherein the AHN does not require immediate
   alternative therapy, such as acute myeloid leukemia. AHNs that are eligible include:
   low grade myelodysplastic syndrome (MDS) with a high SM burden who require treatment
   for SM only, myeloproliferative neoplasms (MPNs), MDS/MPN, and HES/CEL], and MCL i.
   Patients with advanced SM must present with at least 1 eligible C-Finding (organ
   damage) as outlined in Table 3 of the 2013 International Working
   Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European
   Competence Network on Mastocytosis (ECNM) consensus response criteria (Appendix 10.5);
   please see below for MCL exception) (#iii).

   ii. Patients with imatinib-sensitive KIT mutations must have progressed on or were
   intolerant to a tryosine kinase inhibitor.

   iii. Patients with histopathologically-confirmed MCL without a C-finding are eligible.

   iv. Patients with symptomatic SSM are eligible. By definition, SSM patients must have
   at least 2 B-findings, and clinically significant symptom burden (eg, flushing,
   diarrhea, etc.) despite maximal treatment with approved agents to treat mediator
   symptoms, such as antihistamines and cromolyn sodium. Patients must have a normal
   karyotype.

   v. Patients with hematologic malignancies featuring clonal expansion of eosinophils
   driven by genomic alterations of KIT or PDGFR (eg, HES or CEL) must have a diagnosis
   confirmed by a central independent pathologist and are eligible if they have
   progressed on or are intolerant of imatinib therapy. Patients with de novo imatinib
   resistant mutations, such as but not limited to KIT D816V or PDGFRA D842V, are
   eligible without prior imatinib therapy.

   c) Malignant glioma patients with genomic alterations potentially conferring
   sensitivity to DCC-2618 including, but not limited to, amplification and/or mutations
   of PDGFRA and/or KIT.

   i. Patients must not require use of enzyme-inducing antiepileptic drugs. ii. Patients
   that require steroids must be on a stable dose for 2 weeks prior to the first dose of
   study drug.

   d) Other solid tumor patients that have alterations in genes encoding kinases that are
   targets of DCC-2618. This includes KIT, PDGFR (A or B), TIE2, CSF1R, and VEGFR2.
   Patients must have received approved treatments known to provide clinical benefit
   prior to study entry.

   e) If signs or symptoms suggest CNS metastases, a brain MRI must be performed to
   confirm absence of CNS disease within 1 week prior to receiving study drug.

   2. Patients with known CNS metastases may participate provided that:

      1. they are stable (ie, without evidence of progression by magnetic resonance
      imaging [MRI]) for at least 4 weeks prior to the first dose study drug (patients
      with active disease may be eligible following discussion between the Investigator
      and the Sponsor),

      2. all neurologic symptoms have been stable for 2 weeks prior to the first dose of
      study drug,

      3. patients must not require use of enzyme-inducing antiepileptic drugs,

      4. patients that require steroids must be on a stable dose for 2 weeks prior to the
      first dose of study drug.

   3. Patients with solid tumors (with the exception of glial tumors and tumors that are
   anatomically inaccessible) must have an archival tumor biopsy sample as long as no
   anticancer therapy was administered since the sample was collected; otherwise, a
   current biopsy is required. In the case of glial tumors and anatomically inaccessible
   tumors, the most recent archival tissue is required.

   4. Male or female patients ≥18 years of age.

   5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.

   6. Female patients of childbearing potential must have a negative serum beta‑human
   chorionic gonadotropin (β-hCG) pregnancy test within 28 days prior to the start of
   study drug. For clinical sites in the UK, pregnancy testing must occur within 7 days
   prior to the start of study drug.

   7. Patients of reproductive potential must agree to follow the contraception requirements
   outlined in Section 6.8.11.

   8. The patient is capable of understanding and complying with the protocol and has signed
   the informed consent document. A signed informed consent form must be obtained before
   any study‑specific procedures are performed. Standard procedures performed as part of
   the practice of medicine prior to consent (eg, imaging, physical exam) can be used to
   determine eligibility if completed within 28 days prior to the initial dose of study
   drug.

   9. Patients with solid tumors must have at least 1 measurable lesion according to RECIST
   Version 1.1 (non-nodal lesions must be ≥1.0 cm in the long axis or ≥double the slice
   thickness in the long axis; nodal lesions must be ≥1.5 cm in the short axis) or
   Response Assessment in Neuro-Oncology Criteria (RANO).

   a) A non-brain lesion in a previously irradiated area is eligible to be considered as
   measurable disease as long as there is objective evidence of progression of the lesion
   before study enrollment.

10. Adequate organ function and bone marrow function as indicated by the following central
   laboratory screening assessments performed within 14 days prior to the first dose of
   study drug. Local laboratory values obtained after screening and prior to Cycle 1 Day
   1 dosing that do not meet the criteria below must be discussed with the Sponsor:

      1. Solid Tumor Patients: Bone Marrow Function: Absolute neutrophil count (ANC)
      ≥1500/μL; hemoglobin ≥9 g/dL; platelet count ≥75,000/μL.

      2. All Patients:

   i. Hepatic Function: Serum direct bilirubin ≤1.5 times the upper limit of normal (ULN)
   (≤3 × ULN if this elevation is solely due to ASM/MCL); aspartate transaminase
   (AST)/alanine transaminase (ALT), ≤3 × ULN (≤5 × ULN in the presence of hepatic
   metastases or if this elevation is solely due to ASM/MCL).

   ii. Renal Function: Serum creatinine ≤2.0 × ULN or creatinine clearance ≥50 mL/min
   based either on urine collection or Cockcroft Gault estimation.

   iii. Coagulation Profile: Prothrombin time (PT) - international normalized ratio
   (INR)/partial thromboplastin time (PTT) ≤1.5 × ULN. Patients on a stable, maintenance
   regimen of anticoagulant therapy for at least 30 days prior to study drug
   administration may have PT/INR measurements >1.5 × ULN if, in the opinion of the
   Investigator, the patient is suitable for the study. An adequate rationale must be
   provided to the Sponsor prior to enrollment.

   c) SM patients with one or more inadequate organ function laboratory value may be
   eligible if both the Investigator and Sponsor deem it to be disease-related and the
   abnormality qualifies as a C-Finding (see Appendix 10.5).

11. Resolution of all toxicities from prior therapy to ≤Grade 1 (or baseline) within 1
   week prior to the first dose of study drug (excluding alopecia and ≤Grade 3 clinically
   asymptomatic lipase, amylase, and creatine phosphokinase laboratory abnormalities).

Exclusion Criteria (Escalation and Expansion Phases)

Patients meeting any of the following criteria will be excluded from the study:

   1. GIST patients with wild type or unknown KIT or PDGFRA status.

   2. Patients with SM or other hematologic malignancies will be excluded if the following
   apply:

      1. SM patients with wild type KIT mutational status.

      2. SM patients with neutropenia accompanied by fever or infection, or
      thrombocytopenia associated with clinically significant bleeding.

         - Patients with an infection that is well controlled with antibiotics are
         eligible if there is an immediate need for treatment

      3. SM-AHN patients diagnosed with:

   i. SM with MDS (SM-MDS) who require treatment for MDS. ii. Patients requiring
   immediate treatment for AHN. d) Patients with leukemias, with the exception of MCL and
   CEL, that have progressed after imatinib.

   e) Eosinophilic myeloproliferative neoplasm patients: i. Lacking a mutation that is a
   known target of DCC-2618. This includes, but is not limited to, fusions/mutations of
   FGFR1, JAK2, and ABL.

   3. Has a known additional malignancy that is progressing or required active treatment
   within 3 years of the first dose of study treatment. Exceptions include basal cell
   carcinoma of the skin, squamous cell carcinoma of the skin that has undergone
   potentially curative therapy, or other in situ cancers.

   4. Treatment with anticancer therapy, including investigational therapy, within 2 weeks
   prior to the administration of study drug, with the exception of hydroxyurea that is
   allowed to control white blood cell count. For prior therapies with a half-life longer
   than 3 days, the interval must be at least 28 days prior to the first administration
   of study drug.

   5. New York Heart Association class III and IV heart disease, active ischemia or any
   other uncontrolled cardiac condition such as angina pectoris, clinically significant
   cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart
   failure.

   6. Arterial thrombotic or embolic events such as cerebrovascular accident (including
   ischemic attacks) or hemoptysis within 6 months before start of study drug.

   7. Venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg,
   pulmonary embolism) within the 3 months before start of study drug. Patients with
   venous thrombotic events ≥3 months before start of study drug on stable
   anticoagulation therapy are eligible.

   8. Baseline prolongation of the rate-corrected QT interval based on repeated
   demonstration of QT interval corrected by Fridericia's formula (QTcF) >450 ms in males
   or >470 ms in females or history of long QT interval corrected (QTc) syndrome.

   9. LVEF <50% or below the lower limit of normal (whichever is higher).

10. Major surgery within 4 weeks of the first dose of study drug; following major
   surgeries >4 weeks prior to the first dose of study drug, all surgical wounds must be
   healed and free of infection or dehiscence.

11. Any other clinically significant comorbidities, such as uncontrolled pulmonary
   disease, active infection, or any other condition, which in the judgment of the
   Investigator, could compromise compliance with the protocol, interfere with the
   interpretation of study results, or predispose the patient to safety risks.

12. Malabsorption syndrome or other illness that could affect oral absorption.

13. Known human immunodeficiency virus or active hepatitis C infection only if the patient
   is taking medications that are described in Section 5.8.2.2, active hepatitis B, or
   active hepatitis C infection.

14. If female, the patient is pregnant or lactating.

15. Known allergy or hypersensitivity to any component of the investigational drug
   product.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Justin Abuel
650-723-1367
Recruiting

A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies

The purpose of this Phase 1 study is to determine the safety, tolerability, maximum tolerated dose, and (preliminary) effectiveness of oral DCC-2618 in patients with advanced malignancies. The study will also determine the pharmacokinetic and pharmacodynamics profile of oral DCC-2618. The study will consist of an Escalation Phase in patients with advanced malignancies (to test safety and to determine the maximum tolerated dose of the study drug) followed by an Expansion Phase in select tumors (to further test the safety and tolerability and to obtain preliminary evidence of efficacy of the study drug). At Stanford we will be taking part in the expansion phase, for patients with GIST.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Deciphera Pharmaceuticals LLC

Intervention(s):

  • Drug: DCC-2618

Phase:

Phase 1

Eligibility


Inclusion Criteria (Escalation and Expansion Phases)

Patients must meet the following criteria to be eligible to enroll in the study:

   1. Patients must have histologically confirmed solid tumors or hematologic malignancies.
   Eligible patients include the following:

   a) GIST patients must have a KIT and PDGFRA mutation and must have progressed on or
   had an intolerability to at least 1 line of systemic anticancer therapy: i. Patients
   with a pre-existing resistance mutation to an approved line of therapy are eligible.
   For example, imatinib resistant mutations including KIT Exon 17 and PDGFRA D842V.

   b) SM patients must have a confirmed diagnosis (confirmed by a central independent
   pathologist) of advanced SM according to 2016 World Health Organization (WHO) criteria
   for SM and must have documented KIT mutant disease. SM patients must also have a
   normal karyotype.

   Advanced SM includes: ASM, SM-AHN, wherein the AHN does not require immediate
   alternative therapy, such as acute myeloid leukemia. AHNs that are eligible include:
   low grade myelodysplastic syndrome (MDS) with a high SM burden who require treatment
   for SM only, myeloproliferative neoplasms (MPNs), MDS/MPN, and HES/CEL], and MCL i.
   Patients with advanced SM must present with at least 1 eligible C-Finding (organ
   damage) as outlined in Table 3 of the 2013 International Working
   Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European
   Competence Network on Mastocytosis (ECNM) consensus response criteria (Appendix 10.5);
   please see below for MCL exception) (#iii).

   ii. Patients with imatinib-sensitive KIT mutations must have progressed on or were
   intolerant to a tryosine kinase inhibitor.

   iii. Patients with histopathologically-confirmed MCL without a C-finding are eligible.

   iv. Patients with symptomatic SSM are eligible. By definition, SSM patients must have
   at least 2 B-findings, and clinically significant symptom burden (eg, flushing,
   diarrhea, etc.) despite maximal treatment with approved agents to treat mediator
   symptoms, such as antihistamines and cromolyn sodium. Patients must have a normal
   karyotype.

   v. Patients with hematologic malignancies featuring clonal expansion of eosinophils
   driven by genomic alterations of KIT or PDGFR (eg, HES or CEL) must have a diagnosis
   confirmed by a central independent pathologist and are eligible if they have
   progressed on or are intolerant of imatinib therapy. Patients with de novo imatinib
   resistant mutations, such as but not limited to KIT D816V or PDGFRA D842V, are
   eligible without prior imatinib therapy.

   c) Malignant glioma patients with genomic alterations potentially conferring
   sensitivity to DCC-2618 including, but not limited to, amplification and/or mutations
   of PDGFRA and/or KIT.

   i. Patients must not require use of enzyme-inducing antiepileptic drugs. ii. Patients
   that require steroids must be on a stable dose for 2 weeks prior to the first dose of
   study drug.

   d) Other solid tumor patients that have alterations in genes encoding kinases that are
   targets of DCC-2618. This includes KIT, PDGFR (A or B), TIE2, CSF1R, and VEGFR2.
   Patients must have received approved treatments known to provide clinical benefit
   prior to study entry.

   e) If signs or symptoms suggest CNS metastases, a brain MRI must be performed to
   confirm absence of CNS disease within 1 week prior to receiving study drug.

   2. Patients with known CNS metastases may participate provided that:

      1. they are stable (ie, without evidence of progression by magnetic resonance
      imaging [MRI]) for at least 4 weeks prior to the first dose study drug (patients
      with active disease may be eligible following discussion between the Investigator
      and the Sponsor),

      2. all neurologic symptoms have been stable for 2 weeks prior to the first dose of
      study drug,

      3. patients must not require use of enzyme-inducing antiepileptic drugs,

      4. patients that require steroids must be on a stable dose for 2 weeks prior to the
      first dose of study drug.

   3. Patients with solid tumors (with the exception of glial tumors and tumors that are
   anatomically inaccessible) must have an archival tumor biopsy sample as long as no
   anticancer therapy was administered since the sample was collected; otherwise, a
   current biopsy is required. In the case of glial tumors and anatomically inaccessible
   tumors, the most recent archival tissue is required.

   4. Male or female patients ≥18 years of age.

   5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.

   6. Female patients of childbearing potential must have a negative serum beta‑human
   chorionic gonadotropin (β-hCG) pregnancy test within 28 days prior to the start of
   study drug. For clinical sites in the UK, pregnancy testing must occur within 7 days
   prior to the start of study drug.

   7. Patients of reproductive potential must agree to follow the contraception requirements
   outlined in Section 6.8.11.

   8. The patient is capable of understanding and complying with the protocol and has signed
   the informed consent document. A signed informed consent form must be obtained before
   any study‑specific procedures are performed. Standard procedures performed as part of
   the practice of medicine prior to consent (eg, imaging, physical exam) can be used to
   determine eligibility if completed within 28 days prior to the initial dose of study
   drug.

   9. Patients with solid tumors must have at least 1 measurable lesion according to RECIST
   Version 1.1 (non-nodal lesions must be ≥1.0 cm in the long axis or ≥double the slice
   thickness in the long axis; nodal lesions must be ≥1.5 cm in the short axis) or
   Response Assessment in Neuro-Oncology Criteria (RANO).

   a) A non-brain lesion in a previously irradiated area is eligible to be considered as
   measurable disease as long as there is objective evidence of progression of the lesion
   before study enrollment.

10. Adequate organ function and bone marrow function as indicated by the following central
   laboratory screening assessments performed within 14 days prior to the first dose of
   study drug. Local laboratory values obtained after screening and prior to Cycle 1 Day
   1 dosing that do not meet the criteria below must be discussed with the Sponsor:

      1. Solid Tumor Patients: Bone Marrow Function: Absolute neutrophil count (ANC)
      ≥1500/μL; hemoglobin ≥9 g/dL; platelet count ≥75,000/μL.

      2. All Patients:

   i. Hepatic Function: Serum direct bilirubin ≤1.5 times the upper limit of normal (ULN)
   (≤3 × ULN if this elevation is solely due to ASM/MCL); aspartate transaminase
   (AST)/alanine transaminase (ALT), ≤3 × ULN (≤5 × ULN in the presence of hepatic
   metastases or if this elevation is solely due to ASM/MCL).

   ii. Renal Function: Serum creatinine ≤2.0 × ULN or creatinine clearance ≥50 mL/min
   based either on urine collection or Cockcroft Gault estimation.

   iii. Coagulation Profile: Prothrombin time (PT) - international normalized ratio
   (INR)/partial thromboplastin time (PTT) ≤1.5 × ULN. Patients on a stable, maintenance
   regimen of anticoagulant therapy for at least 30 days prior to study drug
   administration may have PT/INR measurements >1.5 × ULN if, in the opinion of the
   Investigator, the patient is suitable for the study. An adequate rationale must be
   provided to the Sponsor prior to enrollment.

   c) SM patients with one or more inadequate organ function laboratory value may be
   eligible if both the Investigator and Sponsor deem it to be disease-related and the
   abnormality qualifies as a C-Finding (see Appendix 10.5).

11. Resolution of all toxicities from prior therapy to ≤Grade 1 (or baseline) within 1
   week prior to the first dose of study drug (excluding alopecia and ≤Grade 3 clinically
   asymptomatic lipase, amylase, and creatine phosphokinase laboratory abnormalities).

Exclusion Criteria (Escalation and Expansion Phases)

Patients meeting any of the following criteria will be excluded from the study:

   1. GIST patients with wild type or unknown KIT or PDGFRA status.

   2. Patients with SM or other hematologic malignancies will be excluded if the following
   apply:

      1. SM patients with wild type KIT mutational status.

      2. SM patients with neutropenia accompanied by fever or infection, or
      thrombocytopenia associated with clinically significant bleeding.

         - Patients with an infection that is well controlled with antibiotics are
         eligible if there is an immediate need for treatment

      3. SM-AHN patients diagnosed with:

   i. SM with MDS (SM-MDS) who require treatment for MDS. ii. Patients requiring
   immediate treatment for AHN. d) Patients with leukemias, with the exception of MCL and
   CEL, that have progressed after imatinib.

   e) Eosinophilic myeloproliferative neoplasm patients: i. Lacking a mutation that is a
   known target of DCC-2618. This includes, but is not limited to, fusions/mutations of
   FGFR1, JAK2, and ABL.

   3. Has a known additional malignancy that is progressing or required active treatment
   within 3 years of the first dose of study treatment. Exceptions include basal cell
   carcinoma of the skin, squamous cell carcinoma of the skin that has undergone
   potentially curative therapy, or other in situ cancers.

   4. Treatment with anticancer therapy, including investigational therapy, within 2 weeks
   prior to the administration of study drug, with the exception of hydroxyurea that is
   allowed to control white blood cell count. For prior therapies with a half-life longer
   than 3 days, the interval must be at least 28 days prior to the first administration
   of study drug.

   5. New York Heart Association class III and IV heart disease, active ischemia or any
   other uncontrolled cardiac condition such as angina pectoris, clinically significant
   cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart
   failure.

   6. Arterial thrombotic or embolic events such as cerebrovascular accident (including
   ischemic attacks) or hemoptysis within 6 months before start of study drug.

   7. Venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg,
   pulmonary embolism) within the 3 months before start of study drug. Patients with
   venous thrombotic events ≥3 months before start of study drug on stable
   anticoagulation therapy are eligible.

   8. Baseline prolongation of the rate-corrected QT interval based on repeated
   demonstration of QT interval corrected by Fridericia's formula (QTcF) >450 ms in males
   or >470 ms in females or history of long QT interval corrected (QTc) syndrome.

   9. LVEF <50% or below the lower limit of normal (whichever is higher).

10. Major surgery within 4 weeks of the first dose of study drug; following major
   surgeries >4 weeks prior to the first dose of study drug, all surgical wounds must be
   healed and free of infection or dehiscence.

11. Any other clinically significant comorbidities, such as uncontrolled pulmonary
   disease, active infection, or any other condition, which in the judgment of the
   Investigator, could compromise compliance with the protocol, interfere with the
   interpretation of study results, or predispose the patient to safety risks.

12. Malabsorption syndrome or other illness that could affect oral absorption.

13. Known human immunodeficiency virus or active hepatitis C infection only if the patient
   is taking medications that are described in Section 5.8.2.2, active hepatitis B, or
   active hepatitis C infection.

14. If female, the patient is pregnant or lactating.

15. Known allergy or hypersensitivity to any component of the investigational drug
   product.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Justin Abuel
650-723-1367
Recruiting