Combining Olomorasib and Pembrolizumab for Advanced KRAS G12C-Mutant Lung Cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This study evaluates the effectiveness of the drug LY3537982 in combination with Pembrolizumab, with or without chemotherapy, for patients with untreated advanced non-small cell lung cancer (NSCLC) that has a specific genetic mutation (KRAS G12C). Participants will be randomized into different treatment groups, and the study will assess the safety and efficacy of these combinations over a follow-up period of up to three years. The goal is to determine if this new combination therapy offers better outcomes compared to standard treatments.

Why it matters

Who can join: the full rules

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%.
  * 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

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.

Where it's running

• Clearview Cancer Institute
  Huntsville, Alabama, United States Recruiting
• Banner MD Anderson Cancer Center
  Gilbert, Arizona, United States Recruiting
• Banner University Medical Center Phoenix
  Phoenix, Arizona, United States Recruiting
• The University of Arizona Cancer Center - North Campus
  Tucson, Arizona, United States Recruiting
• Highlands Oncology Group
  Springdale, Arkansas, United States Recruiting
• Cedars-Sinai Medical Center
  Los Angeles, California, United States Recruiting

+365 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
• Email: LillyTrials@Lilly.com
• Phone: 1-317-615-4559

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.