A Study of Inlexisertib (DCC-3116) in Combination With Anticancer Therapies in Participants With Advanced Malignancies

A Master Protocol for the Multi-Cohort, Phase 1/2 Study of DCC-3116 in Combination With Anticancer Therapies in Participants With Advanced Malignancies

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

Inclusion Criteria:

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

Module A Part 1 and Part 2 inlexisertib 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

• Must have at least 1 measurable lesion according to Modified Response Evaluation Criteria in Solid Tumors (mRECIST)

• 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, if able

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

• 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