Clinical trial NCT05957367: A Study of Inlexisertib (DCC-3116) in Combination With Anticancer Therapies in Participants With Advanced Malignancies
Official title: A Master Protocol for the Multi-Cohort, Phase 1/2 Study of DCC-3116 in Combination With Anticancer Therapies in Participants With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: GIST
Keywords: Advanced gastrointestinal stromal tumors
gastrointestinal stromal tumors
ripretinib
Lead sponsor: Deciphera Pharmaceuticals, LLC
Sponsor class: INDUSTRY
First posted: 2023-07-24
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Adverse Events (Escalation Phase)
timeFrame: Approximately 24 months
measure: Recommended Phase 2 Doses (RP2D) (Escalation Phase)
timeFrame: Approximately 18 months
measure: Objective response rate (ORR) (Expansion Phase)
timeFrame: Approximately 24 months
Secondary outcomes:
measure: Duration of response (DoR)
timeFrame: Approximately 24 months
measure: Disease Control Rate (DCR)
timeFrame: Approximately 24 months
measure: Time to response
timeFrame: Approximately 24 months
measure: Progression-free survival (PFS)
timeFrame: Approximately 24 months
measure: Overall Survival (OS)
timeFrame: Approximately 48 months
measure: Maximum observed concentration (Cmax)
timeFrame: Predose and up to 12 hours postdose
measure: Time to maximum observed concentration (Tmax)
timeFrame: Predose and up to 12 hours postdose
measure: Minimum observed concentration (Cmin)
timeFrame: Predose and up to 12 hours postdose
measure: Area under the concentration-time curve (AUC)
timeFrame: Predose and up to 12 hours postdose
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California - Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA Department of Medicine-Hematology/Oncology
state: California
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Siteman Cancer Center
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center - Main Campus
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
Study officials:
affiliation: Deciphera Pharmaceuticals, LLC
name: Clinical Team
role: STUDY_DIRECTOR
References: