A Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung Cancer

Inclusion Criteria

• Histologically or cytologically confirmed NSCLC with Stage IIIB-IIIC or Stage IV disease, not suitable for curative intent radical surgery or radiation therapy.
• Part B and Safety Lead-In Part B: the histology of the tumor must be predominantly non-squamous (in line with pemetrexed label).
• Must have disease with evidence of KRAS G12C mutation.
• Must have known programmed death-ligand 1 (PD-L1) expression
• Part A: Greater than or equal to (≥)50 percent (%).
• Part B: 0% to 100%.
• Must have measurable disease per RECIST v1.1.
• Must have an ECOG performance status of 0 or 1.
• Estimated life expectancy ≥12 weeks.
• Ability to swallow capsules.
• 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 a documented additional validated targetable oncogenic driver mutation or alteration in genes such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), BRAF (V600E), human epidermal growth factor receptor 2 (HER2), MET (exon 14), ROS1, rearranged during transfection (RET), or neurotrophic tyrosine receptor kinase (NTRK)1/2/3.
• Have had any of the following prior to randomization: -- Prior systemic therapy (chemotherapy, immunotherapy, targeted therapy, or biological therapy) for advanced or metastatic NSCLC. --- 1 cycle of standard-of-care treatment prior to study enrollment will be allowed for cases where immediate treatment is clinically indicated:
• Have known active central nervous system metastases and/or carcinomatous meningitis. Exclusion Criteria for Participants receiving Pemetrexed and Platinum (Part B and Safety Lead-In Part B)
• Have predominantly squamous cell histology for NSCLC
• Only for participants with mild to moderate renal insufficiency: Unable to avoid aspirin, ibuprofen, or other nonsteroidal anti-inflammatory drugs (NSAIDs) two days before (5 days for long acting NSAIDs), day of, and two days after administration of pemetrexed
• Is unable or unwilling to take folic acid or vitamin B12 supplementation.