Overview
The purpose of this study is to assess if adding LY3537982 in combination with standard of care anti-cancer drugs is more effective than standard of care in participants with untreated advanced NSCLC. NSCLC must have a change in a gene called KRAS G12C. Study participation, including follow-up, could last up to 3 years, depending on how you and your lung cancer are doing.
Description
Dose Optimization, Part A, and Part B are randomized. Safety Lead-In for Part B is single arm, non-randomized.
Eligibility
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.