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

Phase 1

Recruiting

• Conditions: GIST
• Interventions: Drug: Inlexisertib; Drug: Ripretinib

• Registration Number: NCT05957367
• Lead Sponsor: Deciphera Pharmaceuticals, LLC

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-07-14
• Study First Submitted QC: 2023-07-14
• Study First Posted: 2023-07-24
• Study Start: 2023-09-28
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-02
• Last Update Posted: 2025-05-06
• Primary Completion: 2027-03
• Study Completion: 2029-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 94

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Escalation (Part 1, Module A)	Inlexisertib	Escalation Module A Part 1 inlexisertib combination closed on January 8, 2024, with no participants enrolled.
Dose Escalation (Part 1, Module B)	Ripretinib	Inlexisertib tablets in escalating dose cohorts in 28-day cycles will be administered in combination with ripretinib once daily (QD).
Expansion (Part 2, Module A)	Inlexisertib	Expansion Module A Part 2 inlexisertib combination closed on January 8, 2024, with no participants enrolled.
Expansion (Part 2, Module B)	Inlexisertib	Inlexisertib 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).
Dose Escalation (Part 1, Module B)	Inlexisertib	Inlexisertib tablets in escalating dose cohorts in 28-day cycles will be administered in combination with ripretinib once daily (QD).
Expansion (Part 2, Module B)	Ripretinib	Inlexisertib 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).

Primary Outcome Measures

Name	Time	Method
Incidence of Adverse Events (Escalation Phase)	Approximately 24 months	Identify the observed adverse events and serious adverse events associated with inlexisertib in combination with other anticancer therapies.
Recommended Phase 2 Doses (RP2D) (Escalation Phase)	Approximately 18 months	Identify the dose-limiting toxicities for each dose level tested and determine the recommended Phase 2 doses of inlexisertib in combination with other anticancer therapies.
Objective response rate (ORR) (Expansion Phase)	Approximately 24 months	Proportion of participants who achieve CR or PR per histology-specific consensus response criteria.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Approximately 48 months	OS is defined as the time from initiation of treatment until death.
Maximum observed concentration (Cmax)	Predose and up to 12 hours postdose	Measure the maximum observed concentration of inlexisertib combinations.
Time to maximum observed concentration (Tmax)	Predose and up to 12 hours postdose	Measure the time to maximum plasma concentration of inlexisertib combinations.
Minimum observed concentration (Cmin)	Predose and up to 12 hours postdose	Measure the minimum observed concentration of inlexisertib combinations.
Area under the concentration-time curve (AUC)	Predose and up to 12 hours postdose	Measure the AUC of inlexisertib combinations.
Disease Control Rate (DCR)	Approximately 24 months	The DCR is defined as the proportion of participants who achieve CR, PR, or stable disease (SD) per histology-specific consensus response criteria.
Time to response	Approximately 24 months	Time to response is defined as the time from initiation of treatment until the first assessment demonstrating CR or PR per histology-specific consensus response criteria.
Progression-free survival (PFS)	Approximately 24 months	PFS is defined as the time from initiation of treatment until documented disease progression per histology-specific consensus response criteria or death, whichever occurs first.
Duration of response (DoR)	Approximately 24 months	DoR is defined as the time interval from the time that the measurement criteria are first met for CR or PR (whichever is first recorded) per histology-specific consensus response criteria until the first date that the progressive disease is objectively documented or death, whichever occurs first.

Trial Locations

Locations (10)

University of Southern California - Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

UCLA Department of Medicine-Hematology/Oncology; 🇺🇸 Los Angeles, California, United States

Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

START Midwest; 🇺🇸 Grand Rapids, Michigan, United States

Washington University School of Medicine - Siteman Cancer Center; 🇺🇸 Saint Louis, Missouri, United States

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Cancer Center - Main Campus; 🇺🇸 New York, New York, United States

Cleveland Clinic Taussig Cancer Center; 🇺🇸 Cleveland, Ohio, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States