INCB186748: INCB186748 will be administered at protocol defined dose.
Cetuximab: Cetuximab will be administered at protocol defined dose.
GEMNabP: GEMNabP will be administered at protocol defined dose.
mFOLFIRINOX: mFOLFIRINOX will be administered at protocol defined dose.
Study summary
The purpose of this study is to evaluate INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* ≥18 years old.
* Locally advanced or metastatic solid tumor with KRAS G12D mutation.
* For Part 1 and Part 2 Combination Group 1: Disease progression on or after prior standard treatment, or intolerance to or ineligibility for standard treatment, or no standard available treatment to improve the disease outcome.
* For Part 2 Combination Groups 2 and 3: No more than 1 prior standard treatment.
* Cohort-specific requirements as follows:
* Parts 1a and 1d: histologically or cytologically confirmed malignant solid tumor of any tissue origin.
* Part 1b
* Disease Group 1: diagnosis of PDAC and at least 1 but no more than 2 prior standard systemic regimens for pancreatic cancer.
* Disease Group 2: diagnosis of CRC.
* Part 1c: Confirmed diagnosis of PDAC or CRC.
* Parts 2a and 2b
* Combination Group 1 (INCB186748 in combination with cetuximab):
* Diagnosis of PDAC or
* Diagnosis of CRC and ∘ Prior treatment in the advanced setting with a fluoropyrimidine-based chemotherapy regimen containing either oxaliplatin or irinotecan and
* In Part 2a: ≤ 3 prior standard regimens.
* In Part 2b: ≤ 2 prior standard regimens.
* Combination Group 2 (INCB186748 in combination with GEMNabP) and
* Combination Group 3 (INCB186748 in combination with mFOLFIRINOX):
* Diagnosis of PDAC.
* ≤ 1 prior standard systemic regimen for pancreatic cancer.
* Measurable disease according to RECIST v1.1.
* ECOG performance status score of 0 or 1.
Exclusion Criteria:
* Prior treatment with any KRAS inhibitor.
* Known additional invasive malignancy within 1 year of the first dose of study drug.
* History of organ transplant, including allogeneic stem cell transplantation.
* Significant, uncontrolled medical condition.
* History or presence of an ECG abnormality.
* Inadequate organ function.
Other protocol-defined Inclusion/Exclusion Criteria may apply.
Primary outcome measure(s)
Number of participants with Dose Limiting Toxicities (DLTs) — Up to 28 days Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
Number of participants with Treatment-emergent Adverse Events (TEAEs) — Up to approximately 12 months and 60 days Defined as adverse events reported for the first time or worsening of a pre-existing event occurring after the first dose of study drug up to 30 days (for INCB186748 as monotherapy and in combination with GEMNabP or mFOLFIRINOX) and 60 days (for INCB186748 in combination with cetuximab) after the last dose of INCB186748.
Number of participants with TEAEs leading to dose modification or discontinuation — Up to approximately 12 months and 60 days Number of participants with TEAEs leading to dose modification or discontinuation.
Trial sites (9)
Facility
City
Region
Status
UCLA Healthcare Hematology-Oncology
Santa Monica
California
Sarah Cannon Research Institue At Healthone
Denver
Colorado
Georgetown University Hospital
Washington D.C.
District of Columbia
Florida Cancer Specialists
Sarasota
Florida
Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins
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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