A Study to Evaluate INCB161734 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation

Open to people ages 18 years and up

• ≥18 years old
• Locally-advanced or metastatic solid tumor with KRAS G12D mutation
• For Part 1 and Part 2 Combination Groups 1 and 2: Disease progression on prior standard treatment, intolerance to or ineligibility for standard treatment, or no available standard treatment to improve the disease outcome
• For Part 2 Combination Groups 3 and 4: 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 ≤ 2 prior standard systemic regimens for pancreatic cancer
    • Disease group 2: diagnosis of CRC
    • Disease group 3: diagnosis of NSCLC
    • Disease group 4: diagnosis of other advanced solid tumor and not part of Disease groups 1, 2 or 3
  • Part 1c: Confirmed diagnosis of PDAC, CRC, or NSCLC
  • Parts 2A and 2B

    • Combination 1: 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 2: Diagnoses of PDAC, CRC or NSCLC

    • Combination Group 3 (INCB161734 in combination with GEMNabP) and

      Combination Group 4 (INCB161734 in combination with mFOLFIRINOX):

      - Diagnosis of PDAC - ≤ 1 prior standard systemic regimen for pancreatic cancer

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Prior treatment with any KRAS G12D 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