A Study of LY3537982 Plus Immunotherapy With or Without Chemotherapy in Participants With Non-Small Cell Lung Cancer (NSCLC) With a Change in a Gene Called KRAS G12C

• Status: Recruiting
• Trial end date: 2029-10-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Eli Lilly and Company
• Collaborator: Loxo Oncology, Inc.
• Treatments: Carboplatin; Pembrolizumab; Pemetrexed

Criteria

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.