Print

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

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.