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

Prior treatment

• Prior treatment with any KRAS inhibitor.

Other illness

• 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.

Other

• History or presence of an ECG abnormality.
• Inadequate organ function.
  • Other protocol-defined Inclusion/Exclusion Criteria may apply.

• ≥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.