Recruiting

Phase 3

Olomorasib & PembrolizumabA Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung Cancer

Sponsor:

Eli Lilly and Company

Code:

NCT06119581

Conditions

Carcinoma, Non-Small-Cell Lung

Neoplasm Metastasis

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

LY3537982

Pembrolizumab

Placebo

Cisplatin

Carboplatin

Study Details

Brief summary:

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

Study ID

NCT06119581

Start date

Dec 21, 2023

Status verified date

Aug, 2026

Completion date

Jan, 2031

Anticipated

Primary completion date

Nov, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Enrollment

1264 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

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.

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.

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.

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.

experimental: Part B: LY3537982 plus Pembrolizumab, Pemetrexed, and Platinum

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.

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.

Interventions

LY3537982

Administered orally.

Pembrolizumab

Administered IV.

Placebo

Administered orally.

Cisplatin

Administered IV.

Carboplatin

Administered IV.

Pemetrexed

Administered IV.

Primary outcome measure

Dose Optimization and Safety Lead-In Part B: Number of Participants with a Treatment Emergent Adverse Event(s) (TEAE) [ Time Frame: Randomization to first documented progression of disease or death from any cause. (Estimated as approximately 1 year) ]
Part A and Part B: Progression-Free Survival (PFS) [ Time Frame: Randomization to first documented progression of disease or death from any cause. (Estimated as approximately 1 year) ]

Central Contacts and Locations

Central contacts

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

1-317-615-4559 LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

clinical_inquiry_hub@lilly.com

Locations

Clearview Cancer Institute

Recruiting

Huntsville, Alabama, United States, 35805

Contacts

256-705-4224

Principal Investigator:

Marshall Schreeder

Banner MD Anderson Cancer Center

Recruiting

Gilbert, Arizona, United States, 85234

Contacts

602-521-3700

Principal Investigator:

Jiaxin Niu

Banner University Medical Center Phoenix

Recruiting

Phoenix, Arizona, United States, 85006

Principal Investigator:

Jiaxin Niu

The University of Arizona Cancer Center - North Campus

Recruiting

Tucson, Arizona, United States, 85719

Contacts

520-626-3434

Principal Investigator:

Linda Garland

Highlands Oncology Group

Recruiting

Springdale, Arkansas, United States, 72762

Contacts

479-872-8130

Principal Investigator:

Eric Schaefer

Cedars-Sinai Medical Center

Recruiting

Los Angeles, California, United States, 90048

Principal Investigator:

Kamya Sankar

BASS Cancer Center

Recruiting

Walnut Creek, California, United States, 94598

Principal Investigator:

Jewel Johl

USO - Rocky Mountain Cancer Centers

Recruiting

Lone Tree, Colorado, United States, 80124

Contacts

303-925-0700

Principal Investigator:

Robert Jotte

Yale University School of Medicine

Recruiting

New Haven, Connecticut, United States, 06510

Contacts

475-306-2658

Principal Investigator:

So Yeon Kim

Sibley Memorial Hospital

Recruiting

Washington D.C., District of Columbia, United States, 20016

Principal Investigator:

Kristen Marrone

Millennium Oncology Research Clinic

Recruiting

Hollywood, Florida, United States, 33024

Contacts

954-450-1808

Principal Investigator:

Isaac Levy

University of Florida - Jacksonville

Recruiting

Jacksonville, Florida, United States, 32209

Contacts

904-244-4292

Principal Investigator:

Gregory Wynn

Miami Cancer Institute at Baptist Health, Inc.

Recruiting

Miami, Florida, United States, 33176

Principal Investigator:

Bruna Pellini

Ocala Oncology Center PL DBA Florida Cancer Affiliates - Ocala

Recruiting

Ocala, Florida, United States, 34474

Contacts

352-732-4032

Principal Investigator:

Ketan Doshi

Comprehensive Hematology Oncology

Recruiting

St. Petersburg, Florida, United States, 33709

Contacts

727-344-6569

Principal Investigator:

Neeharika Makani

University Cancer & Blood Center, LLC

Recruiting

Athens, Georgia, United States, 30607

Contacts

706-353-2990

Principal Investigator:

PETROS NIKOLINAKOS

Emory University School of Medicine- Grady Campus

Recruiting

Atlanta, Georgia, United States, 30303

Contacts

404-251-5544

Principal Investigator:

Ticiana Leal

Winship Cancer Institute, Emory University

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

404-251-5544

Principal Investigator:

Ticiana Leal

University of Illinois at Chicago

Recruiting

Chicago, Illinois, United States, 60612

Principal Investigator:

Frank Weinberg

University of Chicago Hospital

Recruiting

Chicago, Illinois, United States, 60637

Contacts

773-702-9901

Principal Investigator:

Marina Garassino

Springfield Clinic Main Campus

Recruiting

Springfield, Illinois, United States, 62702

Principal Investigator:

Preet Singh

Parkview Research Center at Parkview Regional Medical Center

Recruiting

Fort Wayne, Indiana, United States, 46845

Principal Investigator:

patricia Rich

Indiana University Melvin and Bren Simon Cancer Center

Recruiting

Indianapolis, Indiana, United States, 46202

Principal Investigator:

Gregory Durm

Franciscan Health

Recruiting

Indianapolis, Indiana, United States, 46237

Contacts

317-859-5252

Principal Investigator:

Harsha Ranganath

Community Cancer Center North

Recruiting

Indianapolis, Indiana, United States, 46250

Contacts

317-621-3858

Principal Investigator:

Natraj Ammakkanavar

The University of Kansas Cancer Center - Westwood

Recruiting

Westwood, Kansas, United States, 66205

Contacts

913-588-6029

Principal Investigator:

Chao Huang

CHI Saint Joseph Cancer Center - East

Recruiting

Lexington, Kentucky, United States, 40509

Principal Investigator:

Nicola Jabbour

University of Kentucky Chandler Medical Center

Recruiting

Lexington, Kentucky, United States, 40536

Contacts

859-257-9568

Principal Investigator:

Susanne Arnold

Mary Bird Perkins Cancer Center

Recruiting

Baton Rouge, Louisiana, United States, 70809

Contacts

225-215-1185

Principal Investigator:

Victor Lin

Johns Hopkins Bayview Medical Center

Recruiting

Baltimore, Maryland, United States, 21224

Principal Investigator:

Kristen Marrone

USO - Maryland Oncology Hematology

Recruiting

Columbia, Maryland, United States, 21044

Principal Investigator:

Benjamin Bridges

Boston Medical Center

Recruiting

Boston, Massachusetts, United States, 02118

Contacts

617-638-7584

Principal Investigator:

Umit Tapan

Lahey Hospital & Medical Center

Recruiting

Burlington, Massachusetts, United States, 01805

Contacts

781-744-8400

Principal Investigator:

Andrew Piper-Vallillo

University of Michigan

Recruiting

Ann Arbor, Michigan, United States, 48109

Principal Investigator:

Angel Qin

The Cancer & Hematology Centers

Recruiting

Grand Rapids, Michigan, United States, 49503

Principal Investigator:

Eric Santos

Allina Health Cancer Institute - Abbott Northwestern Hospital

Recruiting

Minneapolis, Minnesota, United States, 55407

Principal Investigator:

Charlene Fares

HealthPartners Cancer Research Center

Recruiting

Saint Paul, Minnesota, United States, 55101

Principal Investigator:

Kurt Demel

North Mississippi Hematology and Oncology Associates

Recruiting

Tupelo, Mississippi, United States, 38801

Principal Investigator:

Amit Jain

Oncology Hematology Associates

Recruiting

Springfield, Missouri, United States, 65807

Contacts

417-882-4880

Principal Investigator:

Viran Holden

Comprehensive Cancer Centers of Nevada

Recruiting

Las Vegas, Nevada, United States, 89169

Principal Investigator:

Liawaty Ho

Dartmouth-Hitchcock Medical Center

Recruiting

Lebanon, New Hampshire, United States, 03756

Principal Investigator:

Konstantin Dragnev

The Valley Hospital, Inc.

Recruiting

Paramus, New Jersey, United States, 07652

Principal Investigator:

Eli Kirshner

University of New Mexico Comprehensive Cancer Center

Recruiting

Albuquerque, New Mexico, United States, 87131

Principal Investigator:

Moises Harari Turquie

Maimonides Cancer Center

Recruiting

Brooklyn, New York, United States, 11220

Contacts

718-765-2600

Principal Investigator:

Julie Huang

Northwell Health/ RJ Zuckerberg Cancer Center

Recruiting

Lake Success, New York, United States, 11042

Principal Investigator:

Alexander Barbaro

Perlmutter Cancer Center at NYU Langone Hospital - Long Island

Recruiting

Mineola, New York, United States, 11501

Contacts

212-731-6363

Principal Investigator:

Joshua Sabari

Laura and Isaac Perlmutter Cancer Center

Recruiting

New York, New York, United States, 10016

Contacts

212-731-6363

Principal Investigator:

Joshua Sabari

Manhattan Eye, Ear and Throat Hospital

Recruiting

New York, New York, United States, 10065

Principal Investigator:

Alexander Barbaro

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Principal Investigator:

Kathryn Arbour

University of North Carolina Medical Center

Recruiting

Chapel Hill, North Carolina, United States, 27599

Principal Investigator:

Shetal Patel

Duke Cancer Institute

Recruiting

Durham, North Carolina, United States, 27710

Principal Investigator:

Jeffrey Clarke

USO - Oncology Hematology Care

Recruiting

Cincinnati, Ohio, United States, 45242

Principal Investigator:

Patrick Ward

The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer -T

Recruiting

Columbus, Ohio, United States, 43210

Contacts

614-293-3300

Principal Investigator:

Timothy Burns

USO - Oncology Associates of Oregon

Recruiting

Eugene, Oregon, United States, 97401

Contacts

541-683-5001

Principal Investigator:

James E Butrynski

Asante Rogue Regional Medical Center

Recruiting

Medford, Oregon, United States, 97504

Contacts

541-789-5003

Principal Investigator:

Alison Savage

Providence Portland Medical Center

Recruiting

Portland, Oregon, United States, 97213

Principal Investigator:

Rachel Sanborn

Providence St. Vincent Medical Center

Recruiting

Portland, Oregon, United States, 97225

Principal Investigator:

Rachel Sanborn

Kaiser Permanente Interstate Medical Office Central

Recruiting

Portland, Oregon, United States, 97227

Contacts

503-249-3315

Principal Investigator:

Sandeep Mashru

USO - Alliance Cancer Specialists, PC

Recruiting

Horsham, Pennsylvania, United States, 19044

Principal Investigator:

Joseph Potz

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

Recruiting

Philadelphia, Pennsylvania, United States, 19107

Principal Investigator:

Sarah Gordon

UPMC Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Principal Investigator:

Liza Villaruz

Lifespan Cancer Institute

Recruiting

Providence, Rhode Island, United States, 02903

Principal Investigator:

Christopher Azzoli

Medical University of South Carolina

Recruiting

Charleston, South Carolina, United States, 29425

Principal Investigator:

Mariam Alexander

Prisma Health Cancer Institute

Recruiting

Greenville, South Carolina, United States, 29605

Principal Investigator:

Richard O'Neal

Lexington Medical Center

Recruiting

West Columbia, South Carolina, United States, 29169

Contacts

803-794-7511

Principal Investigator:

Scott Graupner

Tennessee Oncology Chattanooga

Recruiting

Chattanooga, Tennessee, United States, 37404

Principal Investigator:

Wade Iams

University of Tennessee Medical Center

Recruiting

Knoxville, Tennessee, United States, 37920

Contacts

865-305-8780

Principal Investigator:

Ardy Davarifar

Baptist Memorial Hospital-Memphis

Recruiting

Memphis, Tennessee, United States, 38120

Principal Investigator:

Osa Ogbeide

Tennessee Oncology

Recruiting

Nashville, Tennessee, United States, 37203

Principal Investigator:

Wade Iams

USO - US Oncology Research Network

Recruiting

Nashville, Tennessee, United States, 37203

Principal Investigator:

SMO Sarah Cannon Research Inst.

USO - Texas Oncology

Recruiting

Austin, Texas, United States, 78745

Principal Investigator:

James Uyeki

William Beaumont Army Medical Center

Recruiting

Fort Bliss, Texas, United States, 79918

Contacts

915-203-2268

Principal Investigator:

Warren Alexander

Houston Methodist Hospital

Recruiting

Houston, Texas, United States, 77030

Contacts

713-441-9948

Principal Investigator:

Jun Zhang

University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

713-792-6363

Principal Investigator:

Marcelo Vailati Negrao

USO - Texas Oncology

Recruiting

Webster, Texas, United States, 77598

Principal Investigator:

Pavel Levin

The University of Vermont Medical Center Inc.

Recruiting

Burlington, Vermont, United States, 05401

Principal Investigator:

Rohit Singh

University of Virginia Health System

Recruiting

Charlottesville, Virginia, United States, 22903

Contacts

434-924-4251

Principal Investigator:

Ryan Gentzler

USO - Virginia Cancer Specialists

Recruiting

Fairfax, Virginia, United States, 22031

Principal Investigator:

Alexander Spira

VCU Health Adult Outpatient Pavillion

Recruiting

Richmond, Virginia, United States, 23219

Contacts

804-828-7999

Principal Investigator:

Renato Martins

Swedish Cancer Institute - Edmonds

Recruiting

Edmonds, Washington, United States, 98026

Principal Investigator:

Siddhartha Devarakonda

Kadlec Clinic Hematology and Oncology

Recruiting

Kennewick, Washington, United States, 99336

Principal Investigator:

Ying Zhuo

Swedish Medical Center

Recruiting

Seattle, Washington, United States, 98104

Principal Investigator:

Siddhartha Devarakonda

VA Puget Sound Health Care System

Recruiting

Seattle, Washington, United States, 98108

Principal Investigator:

Daniel Wu

USO - Northwest Cancer Specialists

Recruiting

Vancouver, Washington, United States, 98684

Principal Investigator:

Anthony Van Ho

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

Recruiting

Madison, Wisconsin, United States, 53715

Principal Investigator:

Lisa Lepeak

BC Cancer Abbotsford

Recruiting

Abbotsford British Columbia, Canada, V2S 0C2

Principal Investigator:

Jasna Deluce

CIUSSS- saguenay-Lac-Saint-Jean

Recruiting

Chicoutimi, Canada, G7H 5H6

Contacts

4185411000

Principal Investigator:

Jose Luiz Guimaraes

BC Cancer Vancouver

Recruiting

Vancouver, Canada, V5Z 4E6

Principal Investigator:

Jamie Feng

More Information

Sponsor

Eli Lilly and Company

Last update posted

Aug 24, 2026

Last verified

Aug, 2026

Keywords

Advanced Non-Small Cell Lung Cancer
KRAS G12 Lung Cancer
Advanced Lung Cancer
Metastatic Lung Cancer
KRAS G12C inhibitor
KRAS G12C Positive
KRAS Mutation
KRAS G12 Mutation
Lung Cancer Mutation
Olomorasib
Lung Diseases
Neoplastic Processes
Pathologic Processes
Neoplasm Metastasis
Non-Small Cell Lung Cancer
Non-Small Cell Lung Cancer (NSCLC)
Antineoplastic Agents
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Eli Lilly and Company on 2026-08-24.