A Study to Evaluate INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation

A Phase 1, Open-Label, Multicenter Study of INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation

The purpose of this study is to evaluate INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation.

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.