Overview

This is a Phase 1/2, multicenter, open-label (unless otherwise specified in a combination-specific module) study of DCC-3116 in combination with anticancer therapies. Modules within the master protocol are defined according to different combinations of DCC-3116 with other anticancer agents.

Eligibility

Inclusion Criteria:

• Male or female ≥18 years of age
• Module A: Part 1 and Part 2:

        Module A Part 1 and Part 2 DCC-3116 combination closed on January 8, 2024, with no
        participants enrolled.
          -  Module B: Only for Part 1 (Safety/Dose-finding):
               -  Pathologically confirmed diagnosis of GIST with a KIT or platelet-derived growth
                  factor receptor alpha (PDGFRA) mutation
               -  Must have progressed on at least one approved systemic regimen given in the
                  locally advanced or metastatic setting or have documented intolerance to it
               -  Must not have received prior ripretinib treatment
          -  Module B: Only for Part 2 (Expansion)
               -  Pathologically confirmed GIST with documented mutation in KIT exon 11
               -  Must have progressed on imatinib given in the locally advanced or metastatic
                  setting or have been intolerant to imatinib and may not have received additional
                  systemic therapy for GIST
          -  Measurable disease
          -  Must have a life expectancy of more than 3 months and an ECOG performance status of
             0-1
          -  Adequate organ function and bone marrow reserve based on laboratory assessments
             performed at Screening
          -  Must provide a fresh tumor biopsy and an archival tumor tissue sample, if available
          -  Must agree to provide an on treatment biopsy
        Exclusion Criteria:
          -  Must not have received the following within the specified time periods prior to the
             first dose of study drug:
               1. Medications, including anticancer therapies, that are known strong or moderate
                  inhibitors or inducers of CYP3A4 or P-glycoprotein (P-gp) including certain
                  herbal medications (eg, St. John's wort): 14 days or 5×the half-life of the
                  medication (whichever is longer)
               2. Other anticancer therapies and any investigational therapies with a known safety
                  and PK profile: 14 days or 5×the half-life of the medication (whichever is
                  shorter)
               3. Investigational therapies with unknown safety and PK profile: 28 days. If there
                  is enough data on the investigational therapy to assess the risk for drug-drug
                  interactions and late toxicities of prior therapy as low, the Sponsor's Medical
                  Monitor may approve a shorter washout of 14 days
               4. Grapefruit or grapefruit juice: 14 days
          -  Have not recovered from all clinically relevant toxicities from prior therapy
          -  New York Heart Association Class III or IV heart disease, active ischemia, or any
             other uncontrolled cardiac condition, clinically significant cardiac arrhythmia
             requiring therapy, uncontrolled hypertension, congestive heart failure, or myocardial
             infarction within 6 months prior to the first dose of study drug
          -  Symptomatic central nervous system (CNS) metastases or presence of leptomeningeal
             disease
          -  Malabsorption syndrome
          -  Bone disease that requires ongoing treatment or has required treatment within 6 months
             of signing the informed consent form
          -  Radiation for indications other than bone disease must have been completed 4 weeks
             prior to first dose of study drug, unless it consisted of limited field palliative
             radiation, including whole brain radiation, which must have been completed at least 2
             weeks prior to first dose of study drug
          -  Major surgery within 4 weeks of the first dose of study drug
          -  Active HIV, Hepatitis B or Hepatitis C infection