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

NCT02571036 | Completed Phase 1 FDA Drug

• 1 other identifier: DCC-2618-01-001
• Study Type: interventional
• Target: 282
• Locations: 6 countries
• Sites: 26

Brief Summary

This is a Phase 1, open-label, first-in-human (FIH) dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of DCC-2618, administered orally (PO), in adult patients with advanced malignancies. The study consists of 2 parts, a dose-escalation phase, and an expansion phase. All active patients (from both dose-escalation and expansion phases) will then transition into an extension phase.

Conditions

Gastrointestinal Stromal Tumors; Advanced Systemic Mastocytosis; Advanced Cancers

Keywords

Gastrointestinal stromal tumors (GIST); systemic mastocytosis (SM); PDGFR-alpha; KIT; mast cell leukemia (MCL); mast cell disease (MCD); DCC-2618; melanoma; aggressive systemic mastocytosis (ASM); soft tissue sarcoma (STS); germ cell tumors; penile cancer; non-small cell lung carcinoma (NSCLC); renal impairment; malignant gliomas

Outcome Measures

Primary Outcomes (3)

• Safety/tolerability of oral DCC-2618: incidence of adverse events

  Dose limiting toxicities, AEs, SAEs, discontinuation of drug due to toxicity, physical exams and ECOG PS, ophthalmologic examinations, changes from baseline in laboratory parameters, electrocardiograms, LVEF, and vital signs.

  Approximately 24 months

• Determination of the Maximum Tolerated Dose and the Recommended Phase 2 Dose

  18 months

• Expansion Phase: Assess Antitumor Activity of DCC-2618 in all diseases

  Objective response rate (ORR); Disease control rate (DCR)

  Approximately 24 months

Secondary Outcomes (2)

• Determine the PK profile of oral DCC-2618

  Predose and up to 24 hours postdose (Cycle = 28 Days)

• Escalation Phase: Assess Antitumor Activity of DCC-2618 in patients with advanced malignancies

  Approximately 24 months

Study Arms (12)

Escalation

EXPERIMENTAL

Escalation Phase: DCC-2618 tablets in escalating dose cohorts given orally BID (twice daily) every 12 hours or once daily (QD) for repeated 28-day cycles. Participants may continue to receive study drug until discontinuation criteria are met. \[Closed for Enrollment\]

Drug: DCC-2618

Expansion Cohort 1

EXPERIMENTAL

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with GIST who have received 3 prior therapies. \[Closed for Enrollment\]

Drug: DCC-2618

Expansion Cohort 2

EXPERIMENTAL

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with GIST who have received 4 prior therapies. \[Closed for Enrollment\]

Drug: DCC-2618

Expansion Cohort 3

EXPERIMENTAL

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with GIST who have received at least one prior therapy and no more than 2 prior therapies. \[Closed for Enrollment\]

Drug: DCC-2618

Expansion Cohort 4

EXPERIMENTAL

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with systemic mastocytosis and other hematologic malignancies.\[Closed for Enrollment\]

Drug: DCC-2618

Expansion Cohort 5

EXPERIMENTAL

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with malignant gliomas.\[Closed for Enrollment\]

Drug: DCC-2618

Expansion Cohort 6

EXPERIMENTAL

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with other solid tumors. \[Closed for Enrollment\]

Drug: DCC-2618

Expansion Cohort 7

EXPERIMENTAL

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with melanomas. \[Closed for Enrollment\]

Drug: DCC-2618

Expansion Cohort 8

EXPERIMENTAL

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with soft tissue sarcomas.\[Closed for Enrollment\]

Drug: DCC-2618

Expansion Cohort 9

EXPERIMENTAL

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with germ cell, penile cancer and non-small cell lung carcinoma (NSCLC). \[Closed for Enrollment\]

Drug: DCC-2618

Expansion Cohort 10

EXPERIMENTAL

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with GIST and other solid tumors with renal impairment. \[Closed for Enrollment\]

Drug: DCC-2618

Extension Cohort

EXPERIMENTAL

150 mg DCC-2618 given once daily in repeated 28-day cycles for active patients from the Escalation and Extension Phases.

Drug: DCC-2618

Interventions

DCC-2618 DRUG

50 mg formulated tablets

Also known as: ripretinib

Expansion Cohort 1; Expansion Cohort 10; Expansion Cohort 2; Expansion Cohort 3; Expansion Cohort 4; Expansion Cohort 5; Expansion Cohort 6; Expansion Cohort 7; Expansion Cohort 8; Expansion Cohort 9; Extension Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet the following criteria to be eligible to enroll in the study:
• Male or female patients ≥18 years of age.
• Patients must have histologically confirmed solid tumors or hematologic malignancies. Eligible patients include the following:
• 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.
• SM patients must have a confirmed diagnosis of advanced SM according to 2016 World Health Organization (WHO) criteria for SM and must have documented KIT mutant disease. Patients with imatinib-sensitive KIT mutations must have progressed on or were intolerant to a tyrosine kinase inhibitor. Patients with advanced SM must present with at least 1 eligible C-Finding (organ damage) per 2013 International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) \& European Competence Network on Mastocytosis consensus response criteria; please see below for MCL exception.
• Advanced SM includes:
• i. Aggressive SM (ASM)
• ii. SM with associated hematologic neoplasm (SM-AHN), wherein the AHN does not require immediate alternative therapy. AHNs that are eligible include: low grade myelodysplastic syndrome (MDS) with a high SM burden who require treatment for SM only, myeloproliferative neoplasms (MPN), MDS/MPN, unclassifiable MDS, and HES/CEL.
• iii. MCL
• Patients with histopathologically-confirmed MCL without a C-finding are eligible.
• iv. Symptomatic SSM
• 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.
• v. Patients with hematologic malignancies featuring clonal expansion of eosinophils driven by genomic alterations of KIT or PDGFRA (eg, HES or CEL) 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.
• Other solid tumor patients that have alterations in genes encoding kinases that are targets of DCC-2618. This includes:

You may not qualify if:

• Patients meeting any of the following criteria will be excluded from the study:
• GIST patients with wild type or unknown KIT or PDGFRA status.
• Patients with SM or other hematologic malignancies will be excluded if the following apply:
• 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.
• SM-AHN patients diagnosed with:
• i. SM with MDS who require treatment for MDS. ii. Patients requiring immediate treatment for AHN.
• c. Patients with leukemias, with the exception of MCL and CEL, that have progressed after imatinib.
• d. Eosinophilic myeloproliferative neoplasm patients: i. Lacking a mutation that is a known target of DCC-2618.
• Prior or concurrent malignancy whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of DCC-2618. Patients receiving adjuvant cancer treatment are not eligible if those medications are potentially active against GIST or excluded per protocol.
• 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.
• Arterial thrombotic or embolic events such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 6 months before start of study drug.
• 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.
• 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.
• Left ventricular ejection fraction (LVEF) \<50% or below the lower limit of normal (whichever is higher).

Sponsors & Collaborators

• Deciphera Pharmaceuticals, LLC: lead

Study Sites (26)

Honor Health (GIST, mastocytosis, other solid tumors)

Scottsdale, Arizona, 85258, United States

Location

UCLA Hematology Center (mastocytosis)

Los Angeles, California, 90024, United States

Location

UCLA (glial malignancies only)

Los Angeles, California, 90095, United States

Location

Stanford University Comprehensive Cancer Center (GIST)

Palo Alto, California, 94304, United States

Location

Stanford University Hematology Clinic (mastocytosis)

Palo Alto, California, 94305, United States

Location

UCSF (glial malignancies only)

San Francisco, California, 94143, United States

Location

Mayo Clinic (GIST, mastocytosis, glial malignancies, other solid tumors)

Jacksonville, Florida, 32224, United States

Location

University of Miami (GIST, mastocytosis, glial malignancies, other solid tumors)

Miami, Florida, 33136, United States

Location

Dana Farber Cancer Institute (GIST, mastocytosis, glial malignancies, other solid tumors)

Boston, Massachusetts, 02215, United States

Location

Colombia University Medical Center (mastocytosis)

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center (GIST, mastocytosis, glial malignancies, other solid tumors)

New York, New York, 10065, United States

Location

OHSU (GIST & mastocytosis only)

Portland, Oregon, 97239, United States

Location

Fox Chase Cancer Center (GIST only)

Philadelphia, Pennsylvania, 19111, United States

Location

MD Anderson Cancer Center (GIST, mastocytosis, glial malignancies, other solid tumors)

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute (GIST, mastocytosis, glial malignancies, other solid tumors)

Salt Lake City, Utah, 84103, United States

Location

Virginia Commonwealth University School of Medicine (mastocytosis)

Richmond, Virginia, 23219, United States

Location

Princess Margaret Cancer Centre (GIST, other solid tumors)

Toronto, M5G IX5, Canada

Location

Uniklinik RWTH Aachen (mastocytosis, GIST, and other solid tumors)

Aachen, 52074, Germany

Location

HELIOS Klinikum Berlin-Buch (GIST, and other solid tumors)

Berlin, 13125, Germany

Location

Essen University Hospital (mastocytosis, GIST, and other solid tumors)

Essen, 45147, Germany

Location

Freiburg University Hospital (mastocytosis, and other solid tumors)

Freiburg im Breisgau, 79106, Germany

Location

University Medical Centre Mannheim (mastocytosis)

Mannheim, 68167, Germany

Location

University Hospital of Verona (mastocytosis)

Verona, 37134, Italy

Location

Leiden University Medical Center (GIST and other solid tumors)

Leiden, 2333, Netherlands

Location

Guy's Hospital (mastocytosis only)

London, SE1 9RT, United Kingdom

Location

Royal Marsden Hospital (GIST, glial malignancies, other solid tumors)

London, SW3 6JJ, United Kingdom

Location

Related Publications (1)

• Janku F, Abdul Razak AR, Chi P, Heinrich MC, von Mehren M, Jones RL, Ganjoo K, Trent J, Gelderblom H, Somaiah N, Hu S, Rosen O, Su Y, Ruiz-Soto R, Gordon M, George S. Switch Control Inhibition of KIT and PDGFRA in Patients With Advanced Gastrointestinal Stromal Tumor: A Phase I Study of Ripretinib. J Clin Oncol. 2020 Oct 1;38(28):3294-3303. doi: 10.1200/JCO.20.00522. Epub 2020 Aug 17.

  PMID: 32804590 DERIVED

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors; Mastocytosis, Systemic; Leukemia, Mast-Cell; Mast Cell Activation Disorders; Melanoma; Sarcoma; Neoplasms, Germ Cell and Embryonal; Penile Neoplasms; Carcinoma, Non-Small-Cell Lung; Renal Insufficiency; Glioma

Interventions

ripretinib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Mastocytosis; Immune System Diseases; Leukemia; Leukemia, Myeloid, Acute; Leukemia, Myeloid; Hematologic Diseases; Hemic and Lymphatic Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Penile Diseases; Male Urogenital Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial

Study Officials

• Deciphera Pharmaceuticals, LLC

  Deciphera Pharmaceuticals, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2015
• First Posted: October 8, 2015
• Study Start: November 1, 2015
• Primary Completion: April 29, 2022
• Study Completion: April 29, 2022
• Last Updated: December 13, 2023

Record last verified: 2023-12

Locations

US (16); DE (5); CA (1); IT (1); NL (1); GB (2)