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.
Male or female ≥18 years of age
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
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)
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)
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
Grapefruit or grapefruit juice: 14 days
Sequential
Inlexisertib
DrugOral Tablet Formulation
Ripretinib
DrugOral Tablet Formulation
Incidence of Adverse Events (Escalation Phase)
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)
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)
Proportion of participants who achieve CR or PR per histology-specific consensus response criteria.
Duration of response (DoR)
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)
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
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)
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.
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