A Study to Evaluate INCB161734 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 Groups 1 and 2: Disease progression on priorstandard treatment, intolerance to or ineligibility for standard treatment, or noavailable 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 solidtumor of any tissue origin

• Part 1B

• Disease group 1: diagnosis of PDAC and ≤ 2 prior standard systemicregimens 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 ofDisease 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-basedchemotherapy 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) andCombination 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

Exclusion Criteria:

• 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