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 (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.

Conditions

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
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%. - 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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)
Masking Description
Parts A and B are double blind. Dose Optimization, Safety Lead-In for Part B and Part C are open label.

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.
Experimental
Part C: 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.

Recruiting Locations

Clearview Cancer Institute
Huntsville, Alabama 35805
Contact:
256-705-4224

Banner MD Anderson Cancer Center
Gilbert, Arizona 85234

Banner University Medical Center Phoenix
Phoenix, Arizona 85006

The University of Arizona Cancer Center - North Campus
Tucson, Arizona 85719
Contact:
520-626-3434

Highlands Oncology Group
Springdale, Arkansas 72762
Contact:
479-872-8130

Cedars-Sinai Medical Center
Los Angeles, California 90048

Mercy Cancer Center
Merced, California 95340
Contact:
209-564-3607

BASS Cancer Center
Walnut Creek, California 94598

USO - Rocky Mountain Cancer Centers
Lone Tree, Colorado 80124
Contact:
303-925-0700

Yale University School of Medicine
New Haven, Connecticut 06510
Contact:
475-306-2658

Sibley Memorial Hospital
Washington D.C., District of Columbia 20016

Millennium Oncology Research Clinic
Hollywood, Florida 33024
Contact:
954-450-1808

University of Florida - Jacksonville
Jacksonville, Florida 32209
Contact:
904-244-4292

Miami Cancer Institute at Baptist Health, Inc.
Miami, Florida 33176

Ocala Oncology Center PL DBA Florida Cancer Affiliates - Ocala
Ocala, Florida 34474
Contact:
352-732-4032

Comprehensive Hematology Oncology
St. Petersburg, Florida 33709
Contact:
727-344-6569

University Cancer & Blood Center, LLC
Athens, Georgia 30607
Contact:
706-353-2990

Emory University School of Medicine- Grady Campus
Atlanta, Georgia 30303
Contact:
404-251-5544

Winship Cancer Institute, Emory University
Atlanta, Georgia 30322
Contact:
404-251-5544

University of Illinois at Chicago
Chicago, Illinois 60612

University of Chicago Hospital
Chicago, Illinois 60637
Contact:
773-702-9901

Springfield Clinic Main Campus
Springfield, Illinois 62702

Parkview Research Center at Parkview Regional Medical Center
Fort Wayne, Indiana 46845

Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana 46202

Franciscan Health
Indianapolis, Indiana 46237
Contact:
317-859-5252

Community Cancer Center North
Indianapolis, Indiana 46250
Contact:
317-621-3858

The University of Kansas Cancer Center - Westwood
Westwood, Kansas 66205
Contact:
913-588-6029

CHI Saint Joseph Cancer Center - East
Lexington, Kentucky 40509

University of Kentucky Chandler Medical Center
Lexington, Kentucky 40536
Contact:
859-257-9568

Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana 70809
Contact:
225-215-1185

Johns Hopkins Bayview Medical Center
Baltimore, Maryland 21224

USO - Maryland Oncology Hematology
Columbia, Maryland 21044

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

Lahey Hospital & Medical Center
Burlington, Massachusetts 01805
Contact:
781-744-8400

University of Michigan
Ann Arbor, Michigan 48109

Karmanos Cancer Institute
Detroit, Michigan 48201

The Cancer & Hematology Centers
Grand Rapids, Michigan 49503

Allina Health Cancer Institute - Abbott Northwestern Hospital
Minneapolis, Minnesota 55407

HealthPartners Cancer Research Center
Saint Paul, Minnesota 55101

North Mississippi Hematology and Oncology Associates
Tupelo, Mississippi 38801

Oncology Hematology Associates
Springfield, Missouri 65807
Contact:
417-882-4880

Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada 89169

Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire 03756

The Valley Hospital, Inc.
Paramus, New Jersey 07652

University of New Mexico Comprehensive Cancer Center
Albuquerque, New Mexico 87131

Maimonides Cancer Center
Brooklyn, New York 11220
Contact:
718-765-2600

Northwell Health/ RJ Zuckerberg Cancer Center
Lake Success, New York 11042

Perlmutter Cancer Center at NYU Langone Hospital - Long Island
Mineola, New York 11501
Contact:
212-731-6363

Laura and Isaac Perlmutter Cancer Center
New York, New York 10016
Contact:
212-731-6363

Manhattan Eye, Ear and Throat Hospital
New York, New York 10065

Memorial Sloan Kettering Cancer Center
New York, New York 10065

University of North Carolina Medical Center
Chapel Hill, North Carolina 27599

Duke Cancer Institute
Durham, North Carolina 27710

UNC REX Cancer Center
Raleigh, North Carolina 27607

USO - Oncology Hematology Care
Cincinnati, Ohio 45242

The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer -T
Columbus, Ohio 43210
Contact:
614-293-3300

USO - Oncology Associates of Oregon
Eugene, Oregon 97401
Contact:
541-683-5001

Asante Rogue Regional Medical Center
Medford, Oregon 97504
Contact:
541-789-5003

Providence Portland Medical Center
Portland, Oregon 97213

Providence St. Vincent Medical Center
Portland, Oregon 97225

Kaiser Permanente Interstate Medical Office Central
Portland, Oregon 97227
Contact:
503-249-3315

USO - Alliance Cancer Specialists, PC
Horsham, Pennsylvania 19044

Thomas Jefferson University, Sidney Kimmel Cancer Center - Clinical Trials Office
Philadelphia, Pennsylvania 19107

UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania 15232

Lifespan Cancer Institute
Providence, Rhode Island 02903

Medical University of South Carolina
Charleston, South Carolina 29425

Prisma Health Cancer Institute
Greenville, South Carolina 29605

Lexington Medical Center
West Columbia, South Carolina 29169
Contact:
803-794-7511

Tennessee Oncology Chattanooga
Chattanooga, Tennessee 37404

University of Tennessee Medical Center
Knoxville, Tennessee 37920
Contact:
865-305-8780

Baptist Memorial Hospital-Memphis
Memphis, Tennessee 38120

Tennessee Oncology
Nashville, Tennessee 37203

USO - US Oncology Research Network
Nashville, Tennessee 37203

USO - Texas Oncology
Austin, Texas 78745

William Beaumont Army Medical Center
Fort Bliss, Texas 79918
Contact:
915-203-2268

Brooke Army Medical Center
Fort Sam Houston, Texas 78234
Contact:
210-916-3332

Houston Methodist Hospital
Houston, Texas 77030
Contact:
713-441-9948

University of Texas MD Anderson Cancer Center
Houston, Texas 77030
Contact:
713-792-6363

USO - Texas Oncology
Webster, Texas 77598

The University of Vermont Medical Center Inc.
Burlington, Vermont 05401

University of Virginia Health System
Charlottesville, Virginia 22903
Contact:
434-924-4251

USO - Virginia Cancer Specialists
Fairfax, Virginia 22031

VCU Health Adult Outpatient Pavillion
Richmond, Virginia 23219
Contact:
804-828-7999

Swedish Cancer Institute - Edmonds
Edmonds, Washington 98026

Kadlec Clinic Hematology and Oncology
Kennewick, Washington 99336

Swedish Medical Center
Seattle, Washington 98104

VA Puget Sound Health Care System
Seattle, Washington 98108

USO - Northwest Cancer Specialists
Vancouver, Washington 98684

SSM Health Dean Medical Group - South Madison Campus Health Research/Circuit Clinical
Madison, Wisconsin 53715

More Details

NCT ID
NCT06119581
Status
Recruiting
Sponsor
Eli Lilly and Company

Study Contact

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

Detailed Description

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

For help using this page: trialstoday@researchmatch.org or call 855-514-7001

ResearchMatch is funded in part by the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program, led by the NIH’s National Center for Advancing Translational Sciences (NCATS), grants UL1TR000445 and 1U54RR032646-01, and grant U24TR001579 from NCATS and the National Library of Medicine. The content of this website is solely the responsibility of ResearchMatch and Vanderbilt University and does not necessarily represent the official views of the NIH, NCATS, or NLM.

Vanderbilt University Medical Center