A Study 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 priorstandard treatment, or intolerance to or ineligibility for standard treatment, or nostandard 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 solidtumor of any tissue origin.

• Part 1b

• Disease Group 1: diagnosis of PDAC and at least 1 but no more than 2 priorstandard 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 afluoropyrimidine-based chemotherapy regimen containing eitheroxaliplatin 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.