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
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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 outcome measure(s)
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.
Trial sites (28)
Facility
City
Region
Status
University of Southern California - Norris Comprehensive Cancer Center
Los Angeles
California
Recruiting
UCLA Department of Medicine-Hematology/Oncology
Los Angeles
California
Recruiting
Sylvester Comprehensive Cancer Center
Miami
Florida
Recruiting
University of Massachusetts Worcester
Worcester
Massachusetts
Recruiting
START Midwest
Grand Rapids
Michigan
Recruiting
Washington University School of Medicine - Siteman Cancer Center
St Louis
Missouri
Recruiting
Memorial Sloan Kettering Cancer Center - Main Campus
New York
New York
Recruiting
Cleveland Clinic Taussig Cancer Center
Cleveland
Ohio
Recruiting
Oregon Health & Science University
Portland
Oregon
Recruiting
Fox Chase Cancer Center
Philadelphia
Pennsylvania
Recruiting
Virginia Cancer Specialist, PC
Fairfax
Virginia
Recruiting
Aarhus University Hospital
Aarhus
Denmark
Recruiting
Centre Oscar Lambret
Lille
France
Recruiting
Institut Curie, Service d'Oncologie Médicale
Paris
France
Recruiting
Hôpital Européen Georges Pompidou
Paris
France
Recruiting
Universitatsklinikum Franfurt
Frankfurt
Germany
Recruiting
Universitätsklinikum Eppendorf
Hamburg
Germany
Recruiting
AOU Careggi - Padiglione 16 - Piano Terra - Ambulatori Oncologici - Ufficio Trial
Florence
Italy
Recruiting
IRCCS Azienda Ospedaliera Metropolitana
Genova
Italy
Recruiting
Istituto Europeo di Oncologia
Milan
Italy
Recruiting
Antonie Van Leeuwenhoek Hospital
Amsterdam
Netherlands
Recruiting
Radboudumc
Nijmegen
Netherlands
Recruiting
Instituto Português de Oncologia do Porto Francisco Gentil, E.P.E.
Porto
Portugal
Recruiting
ICO Hospitalet
Barcelona
Spain
Recruiting
Hospital Universitario Ramón y Cajal
Madrid
Spain
Recruiting
Hospital Universitario Clinico San Carlos
Madrid
Spain
Recruiting
Hospital Universitario Virgen Del Rocio
Seville
Spain
Recruiting
Inselspital Universitätsklinikum Bern
Bern
Switzerland
Recruiting
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This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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