The main purpose of this study is to assess if olomorasib in combination with pembrolizumab is more effective than the pembrolizumab and placebo combination in part A in participants with resected KRAS G12C-mutant NSCLC and to assess if olomorasib in combination with durvalumab is more effective than the durvalumab and placebo combination in part B in participants with unresectable KRAS G12C-mutant non-small cell lung cancer. The study may last up to 3 years for each participant.

Inclusion Criteria:

• Histological or cytological confirmation of NSCLC.

  • Part A

    1. Clinical Stage II-IIIB (N2) treated with presurgical chemoimmunotherapy, with residual tumor present at time of surgery. Patients with a pathologic complete response are not eligible.
    2. Pathologic Stage II-IIIB (N2) NSCLC treated with initial upfront resection.

  • Part B - Clinical Stage III, unresectable NSCLC, without progression on concurrent platinum-based chemoradiotherapy.

• Must have disease with evidence of KRAS G12C mutation.

• Must have known programmed death-ligand 1 (PD-L1) expression

• Must have an ECOG performance status of 0 or 1.

• Able to swallow oral medication.

• Must have adequate laboratory parameters.

• Contraceptive use should be consistent with local regulations for those participating in clinical studies.

• Women of childbearing potential must

  • Have a negative pregnancy test.
  • Not be breastfeeding during treatment

Exclusion Criteria:

• Have known changes in the EGFR or ALK genes.
• Have another type of cancer that is progressing or required active treatment within the past 2 years before screening.
• Have an active autoimmune disease that required systemic treatment in the past 2 years. Endocrine replacement therapy is allowed.
• Had any immune-related side effect or allergic reaction (Grade 3 or higher) from a previous immunotherapy medicine, or any immune-related side effect greater than Grade 1 that has not resolved. This does not apply for people with hormone-related diseases who are now on stable hormone replacement therapy.

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Both Part A and B are randomized, double-blind, placebo-controlled.