SUNRAY-01, A Global Pivotal Study in Participants With KRAS G12C-Mutant, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Comparing First-Line Treatment of LY3537982 and Pembrolizumab vs Placebo and Pembrolizumab in Those With PD-L1 Expression ≥50% or LY3537982 and Pembrolizumab, Pemetrexed, Platinum vs Placebo and Pembrolizumab, Pemetrexed, Platinum Regardless of PD-L1 Expression

Dose Optimization, Part A, and Part B are randomized. Safety Lead-In for Part B is single arm, non-randomized.

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 and after study intervention for at least 180 days.

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)

• Squamous cell and/or mixed small cell/nonsmall cell histology is not permitted.
• Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs)
• Is unable or unwilling to take folic acid or vitamin B12 supplementation.