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

Deciphera Pharmaceuticals, LLC

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: GIST

Treatments: Drug: Ripretinib; Drug: DCC-3116

Study type: Interventional

Funder types: Industry

Identifiers

NCT05957367

DCC-3116-01-002

Details and patient eligibility

About

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.

Enrollment: 94 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

• 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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94 participants in 4 patient groups

Dose Escalation (Part 1, Module A)

Experimental group

Description:

Escalation Module A Part 1 DCC-3116 combination closed on January 8, 2024, with no participants enrolled.

Treatment:

Drug: DCC-3116

Expansion (Part 2, Module A)

Experimental group

Description:

Expansion Module A Part 2 DCC-3116 combination closed on January 8, 2024, with no participants enrolled.

Treatment:

Drug: DCC-3116

Dose Escalation (Part 1, Module B)

Experimental group

Description:

DCC-3116 tablets in escalating dose cohorts in 28-day cycles will be administered in combination with ripretinib once daily (QD).

Treatment:

Drug: DCC-3116

Drug: Ripretinib

Expansion (Part 2, Module B)

Experimental group

Description:

DCC-3116 tablets will be administered in combination with ripretinib in 28-day cycles to evaluate preliminary efficacy in participants with 2nd-line advanced gastrointestinal stromal tumor (GIST).

Treatment:

Drug: DCC-3116

Drug: Ripretinib