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

Purpose

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.

Conditions

  • Carcinoma, Non-Small-Cell Lung
  • Neoplasm Metastasis

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

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 - Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) - Is unable or unwilling to take folic acid or vitamin B12 supplementation.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Dose Optimization: LY3537982 Dose Level 1 plus Pembrolizumab 		LY3537982 Dose level 1 administered orally in combination with pembrolizumab administered intravenously (IV) in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
  • Drug: LY3537982
    Administered orally.
    Other names:
    • Olomorasib
  • Drug: Pembrolizumab
    Administered IV.
Experimental
Dose Optimization: LY3537982 Dose Level 2 plus Pembrolizumab 		LY3537982 Dose level 2 administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
  • Drug: LY3537982
    Administered orally.
    Other names:
    • Olomorasib
  • Drug: Pembrolizumab
    Administered IV.
Experimental
Safety Lead In: LY3537982 plus Pembrolizumab, Pemetrexed and Platinum 		LY3537982 administered orally in combination with pembrolizumab, pemetrexed, and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
  • Drug: LY3537982
    Administered orally.
    Other names:
    • Olomorasib
  • Drug: Pembrolizumab
    Administered IV.
  • Drug: Cisplatin
    Administered IV.
  • Drug: Carboplatin
    Administered IV.
  • Drug: Pemetrexed
    Administered IV.
Experimental
Part A: LY3537982 plus Pembrolizumab 		LY3537982 administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
  • Drug: LY3537982
    Administered orally.
    Other names:
    • Olomorasib
  • Drug: Pembrolizumab
    Administered IV.
Placebo Comparator
Part A: Placebo plus Pembrolizumab 		Placebo administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
  • Drug: Pembrolizumab
    Administered IV.
  • Drug: Placebo
    Administered orally.
Experimental
Part B: LY3537982 plus Pembrolizumab, Pemetrexed, and Platinum 		LY3537982 administered orally in combination with pembrolizumab, pemetrexed, and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
  • Drug: LY3537982
    Administered orally.
    Other names:
    • Olomorasib
  • Drug: Pembrolizumab
    Administered IV.
  • Drug: Cisplatin
    Administered IV.
  • Drug: Carboplatin
    Administered IV.
  • Drug: Pemetrexed
    Administered IV.
Placebo Comparator
Part B: Placebo plus Pembrolizumab, Pemetrexed, and Platinum 		Placebo administered orally in combination with pembrolizumab, pemetrexed, and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
  • Drug: Pembrolizumab
    Administered IV.
  • Drug: Placebo
    Administered orally.
  • Drug: Cisplatin
    Administered IV.
  • Drug: Carboplatin
    Administered IV.
  • Drug: Pemetrexed
    Administered IV.

Recruiting Locations

Boston Medical Center
Boston, Massachusetts 02118
Contact:
617-638-7584

More Details

Status
Recruiting
Sponsor
Eli Lilly and Company

Study Contact

There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
1-317-615-4559
ClinicalTrials.gov@lilly.com

Detailed Description

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