GIST
Conditions
Keywords
Advanced gastrointestinal stromal tumors, gastrointestinal stromal tumors, ripretinib
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.
Interventions
DRUGInlexisertib
Oral Tablet Formulation
DRUGRipretinib
Oral Tablet Formulation
Sponsors
Deciphera Pharmaceuticals, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
Denmark, France, Germany, Italy, Netherlands, Portugal, Spain, Switzerland, United States
Contacts
CONTACTClinical Team
STUDY_DIRECTORClinical Team
Deciphera Pharmaceuticals, LLC
Outcome results
None listed