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

What this study is about

The purpose of this study is to assess if adding LY3537982 (olomorasib) 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.

Who can join (things the study team will check)

✅ You may be able to join if…

• 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%.
  • Part C: <50%.
• 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

🚫 You may not be able to join if…

• 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.

🚫 You may not be able to join if…

• 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.

Where this trial is running

• Clearview Cancer Institute, Huntsville, Alabama, United States
• Banner MD Anderson Cancer Center, Gilbert, Arizona, United States
• Banner University Medical Center Phoenix, Phoenix, Arizona, United States
• The University of Arizona Cancer Center - North Campus, Tucson, Arizona, United States
• Highlands Oncology Group, Springdale, Arkansas, United States
• Cedars-Sinai Medical Center, Los Angeles, California, United States
• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, United States
• BASS Cancer Center, Walnut Creek, California, United States
• USO - Rocky Mountain Cancer Centers, Lone Tree, Colorado, United States
• Yale University School of Medicine, New Haven, Connecticut, United States
• Sibley Memorial Hospital, Washington D.C., District of Columbia, United States
• Millennium Oncology Research Clinic, Hollywood, Florida, United States

+ 407 more sites.

Who to contact

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or · 1-317-615-4559 · LillyTrials@Lilly.com

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT06119581.