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

About

Brief Summary

This study is conducted to determine the safety and tolerability of INCB161734 as a single agent or in combination with other anticancer therapies.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 1

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

18 Years

Maximum Age

N/A

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 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

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