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RecruitingInterventionalPhase 3

SUNRAY-01, A Global Pivotal Study in Participants With KRAS G12C-Mutant, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Comparing First-Line Treatment of LY3537982 and Pembrolizumab vs Placebo and Pembrolizumab in Those With PD-L1 Expression ≥50% or LY3537982 and Pembrolizumab, Pemetrexed, Platinum vs Placebo and Pembrolizumab, Pemetrexed, Platinum Regardless of PD-L1 Expression

NCT ID: NCT06119581Sponsor: Eli Lilly and CompanyLast updated: 2026-06-18

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.

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.

Arms & interventions

  • DrugLY3537982

    Administered orally.

  • DrugPembrolizumab

    Administered IV.

  • DrugPlacebo

    Administered orally.

  • DrugCisplatin

    Administered IV.

  • DrugCarboplatin

    Administered IV.

  • DrugPemetrexed

    Administered IV.

Outcome measures

Primary

  • Dose Optimization and Safety Lead-In Part B: Number of Participants with a Treatment Emergent Adverse Event(s) (TEAE)

    Dose Optimization and Safety Lead-In Part B: Number of Participants with a 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)

    PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent central review (BICR)

    Time frame: Randomization to first documented progression of disease or death from any cause. (Estimated as approximately 1 year)

Secondary

  • Part A and Part B: Overall Survival (OS)

    Time frame: Randomization to date of death from any cause. (Estimated as up to 3 years)

  • Part A and Part B: PFS

    Time frame: Randomization to first documented progression of disease or death from any cause. (Estimated as approximately 1 year)

  • Part A and Part B: Overall Response Rate (ORR): Percentage of Participants who Achieve a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR)

    Time frame: Randomization to disease progression or death. (Estimated as approximately 1 year)

  • Part A and Part B: Duration of Response (DOR)

    Time frame: Date of first evidence of CR or PR to date of disease progression or death from any cause. (Estimated as approximately 1 year)

  • Part A and Part B: Disease Control Rate (DCR): Percentage of Participants who Achieve a BOR of CR, PR, or Stable Disease (SD)

    Time frame: Randomization to disease progression or death from any cause. (Estimated as approximately 1 year)

  • Part A and Part B: Time to Response (TTR)

    Time frame: Time from randomization until the date that measurement criteria for CR or PR (whichever is first recorded) are first met (Estimated as approximately 1 year)

  • Part A and Part B: Intracranial Overall Response Rate (ORR)

    Time frame: Randomization to intracranial disease progression or death. (Estimated as approximately 1 year)

  • Part A and Part B: Intracranial Duration of Response (DoR)

    Time frame: Date of first evidence of CR or PR to date of intracranial disease progression or death from any cause. (Estimated as approximately 1 year)

  • Part A and Part B: PFS2

    Time frame: Randomization to disease progression on next line of treatment or death from any cause (Estimated as approximately 1 year

  • Part A and Part B: Changes in NSCLC-related symptoms as measured by NSCLC-SAQ

    Time frame: Randomization through end of treatment (Estimated as approximately 1 year)]

  • Part A and Part B: Time to Worsening of NSCLC-related Symptoms as Measured by NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ)

    Time frame: Randomization through end of treatment (Estimated as approximately 1 year)

  • Part A and Part B: Changes in physical function, as measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) Physical Functioning subscale and IL19

    Time frame: Randomization through end of treatment (Estimated as approximately 1 year)

  • Part A and Part B: Time to Deterioration in Physical Function, as Measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) Physical Functioning Subscale and IL19

    Time frame: Randomization through end of treatment (Estimated as approximately 1 year)

  • Part A and Part B: Proportion of Time with High Side-Effect Burden, as Measured by Functional Assessment of Cancer Therapy - General Item 5 (FACT-GP5)

    Time frame: Randomization through end of treatment (Estimated as approximately 1 year)

  • Part A and Part B: Change from Baseline in Overall Health-related Quality of Life, as Measured by the EORTC QLQ-C30 Global Health Status/Quality of Life Subscale

    Time frame: Randomization through end of treatment (Estimated as approximately 1 year)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy 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 locations (90)

Clearview Cancer Institute

Huntsville, Alabama, 35805

Recruiting
· Contact
Marshall Schreeder · Principal Investigator

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234

Recruiting
Jiaxin Niu · Principal Investigator

Banner University Medical Center Phoenix

Phoenix, Arizona, 85006

Recruiting
Jiaxin Niu · Principal Investigator

The University of Arizona Cancer Center - North Campus

Tucson, Arizona, 85719

Recruiting
· Contact
Linda Garland · Principal Investigator

Highlands Oncology Group

Springdale, Arkansas, 72762

Recruiting
· Contact
Eric Schaefer · Principal Investigator

Cedars-Sinai Medical Center

Los Angeles, California, 90048

Recruiting
Kamya Sankar · Principal Investigator

Mercy Cancer Center

Merced, California, 95340

Recruiting
· Contact
Parminder Sidhu · Principal Investigator

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Torrance, California, 90502

Completed

BASS Cancer Center

Walnut Creek, California, 94598

Recruiting
Jewel Johl · Principal Investigator

USO - Rocky Mountain Cancer Centers

Lone Tree, Colorado, 80124

Recruiting
· Contact
Robert Jotte · Principal Investigator

Yale University School of Medicine

New Haven, Connecticut, 06510

Recruiting
· Contact
So Yeon Kim · Principal Investigator

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016

Recruiting
Kristen Marrone · Principal Investigator

Millennium Oncology Research Clinic

Hollywood, Florida, 33024

Recruiting
· Contact
Isaac Levy · Principal Investigator

University of Florida - Jacksonville

Jacksonville, Florida, 32209

Recruiting
· Contact
Gregory Wynn · Principal Investigator

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, 33176

Recruiting
Bruna Pellini · Principal Investigator

Ocala Oncology Center PL DBA Florida Cancer Affiliates - Ocala

Ocala, Florida, 34474

Recruiting
· Contact
Ketan Doshi · Principal Investigator

Orlando Health Cancer Institute

Orlando, Florida, 32806

Not Yet Recruiting
Yuanbin Chen · Principal Investigator

Comprehensive Hematology Oncology

St. Petersburg, Florida, 33709

Recruiting
· Contact
Neeharika Makani · Principal Investigator

University Cancer & Blood Center, LLC

Athens, Georgia, 30607

Recruiting
· Contact
PETROS NIKOLINAKOS · Principal Investigator

Emory University School of Medicine- Grady Campus

Atlanta, Georgia, 30303

Recruiting
· Contact
Ticiana Leal · Principal Investigator

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322

Recruiting
· Contact
Ticiana Leal · Principal Investigator

University of Illinois at Chicago

Chicago, Illinois, 60612

Recruiting
Frank Weinberg · Principal Investigator

University of Chicago Hospital

Chicago, Illinois, 60637

Recruiting
· Contact
Marina Garassino · Principal Investigator

Springfield Clinic Main Campus

Springfield, Illinois, 62702

Recruiting
Preet Singh · Principal Investigator

Parkview Research Center at Parkview Regional Medical Center

Fort Wayne, Indiana, 46845

Recruiting
patricia Rich · Principal Investigator

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202

Recruiting
Gregory Durm · Principal Investigator

Franciscan Health

Indianapolis, Indiana, 46237

Recruiting
· Contact
Harsha Ranganath · Principal Investigator

Community Cancer Center North

Indianapolis, Indiana, 46250

Recruiting
· Contact
Natraj Ammakkanavar · Principal Investigator

The University of Kansas Cancer Center - Westwood

Westwood, Kansas, 66205

Recruiting
· Contact
Chao Huang · Principal Investigator

CHI Saint Joseph Cancer Center - East

Lexington, Kentucky, 40509

Recruiting
Nicola Jabbour · Principal Investigator

University of Kentucky Chandler Medical Center

Lexington, Kentucky, 40536

Recruiting
· Contact
Susanne Arnold · Principal Investigator

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, 70809

Recruiting
· Contact
Victor Lin · Principal Investigator

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224

Recruiting
Kristen Marrone · Principal Investigator

USO - Maryland Oncology Hematology

Columbia, Maryland, 21044

Recruiting
Benjamin Bridges · Principal Investigator

Boston Medical Center

Boston, Massachusetts, 02118

Recruiting
· Contact
Umit Tapan · Principal Investigator

Lahey Hospital & Medical Center

Burlington, Massachusetts, 01805

Recruiting
· Contact
Andrew Piper-Vallillo · Principal Investigator

University of Michigan

Ann Arbor, Michigan, 48109

Recruiting
Angel Qin · Principal Investigator

The Cancer & Hematology Centers

Grand Rapids, Michigan, 49503

Recruiting
Eric Santos · Principal Investigator

Allina Health Cancer Institute - Abbott Northwestern Hospital

Minneapolis, Minnesota, 55407

Recruiting
Charlene Fares · Principal Investigator

HealthPartners Cancer Research Center

Saint Paul, Minnesota, 55101

Recruiting
Kurt Demel · Principal Investigator

North Mississippi Hematology and Oncology Associates

Tupelo, Mississippi, 38801

Recruiting
Amit Jain · Principal Investigator

Oncology Hematology Associates

Springfield, Missouri, 65807

Recruiting
· Contact
Viran Holden · Principal Investigator

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169

Recruiting
Liawaty Ho · Principal Investigator

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756

Recruiting
Konstantin Dragnev · Principal Investigator

The Valley Hospital, Inc.

Paramus, New Jersey, 07652

Recruiting
Eli Kirshner · Principal Investigator

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87131

Recruiting
Moises Harari Turquie · Principal Investigator

Maimonides Cancer Center

Brooklyn, New York, 11220

Recruiting
· Contact
Julie Huang · Principal Investigator

Northwell Health/ RJ Zuckerberg Cancer Center

Lake Success, New York, 11042

Recruiting
Alexander Barbaro · Principal Investigator

Perlmutter Cancer Center at NYU Langone Hospital - Long Island

Mineola, New York, 11501

Recruiting
· Contact
Joshua Sabari · Principal Investigator

Laura and Isaac Perlmutter Cancer Center

New York, New York, 10016

Recruiting
· Contact
Joshua Sabari · Principal Investigator

Manhattan Eye, Ear and Throat Hospital

New York, New York, 10065

Recruiting
Alexander Barbaro · Principal Investigator

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Recruiting
Kathryn Arbour · Principal Investigator

University of North Carolina Medical Center

Chapel Hill, North Carolina, 27599

Recruiting
Shetal Patel · Principal Investigator

Duke Cancer Institute

Durham, North Carolina, 27710

Recruiting
Jeffrey Clarke · Principal Investigator

Miami Valley Hospital South

Centerville, Ohio, 45459

Not Yet Recruiting
tarek sabagh · Principal Investigator

USO - Oncology Hematology Care

Cincinnati, Ohio, 45242

Recruiting
Patrick Ward · Principal Investigator

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

Columbus, Ohio, 43210

Recruiting
· Contact
Timothy Burns · Principal Investigator

USO - Oncology Associates of Oregon

Eugene, Oregon, 97401

Recruiting
· Contact
James E Butrynski · Principal Investigator

Asante Rogue Regional Medical Center

Medford, Oregon, 97504

Recruiting
· Contact
Alison Savage · Principal Investigator

Providence Portland Medical Center

Portland, Oregon, 97213

Recruiting
Rachel Sanborn · Principal Investigator

Providence St. Vincent Medical Center

Portland, Oregon, 97225

Recruiting
Rachel Sanborn · Principal Investigator

Kaiser Permanente Interstate Medical Office Central

Portland, Oregon, 97227

Recruiting
· Contact
Sandeep Mashru · Principal Investigator

USO - Alliance Cancer Specialists, PC

Horsham, Pennsylvania, 19044

Recruiting
Joseph Potz · Principal Investigator

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

Philadelphia, Pennsylvania, 19107

Recruiting
Sarah Gordon · Principal Investigator

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

Recruiting
Liza Villaruz · Principal Investigator

Lifespan Cancer Institute

Providence, Rhode Island, 02903

Recruiting
Christopher Azzoli · Principal Investigator

Medical University of South Carolina

Charleston, South Carolina, 29425

Recruiting
Mariam Alexander · Principal Investigator

Prisma Health Cancer Institute

Greenville, South Carolina, 29605

Recruiting
Richard O'Neal · Principal Investigator

Lexington Medical Center

West Columbia, South Carolina, 29169

Recruiting
· Contact
Scott Graupner · Principal Investigator

Tennessee Oncology Chattanooga

Chattanooga, Tennessee, 37404

Recruiting
Wade Iams · Principal Investigator

University of Tennessee Medical Center

Knoxville, Tennessee, 37920

Recruiting
· Contact
Ardy Davarifar · Principal Investigator

Baptist Memorial Hospital-Memphis

Memphis, Tennessee, 38120

Recruiting
Osa Ogbeide · Principal Investigator

Tennessee Oncology

Nashville, Tennessee, 37203

Recruiting
Wade Iams · Principal Investigator

USO - US Oncology Research Network

Nashville, Tennessee, 37203

Recruiting
SMO Sarah Cannon Research Inst. · Principal Investigator

USO - Texas Oncology

Austin, Texas, 78745

Recruiting
James Uyeki · Principal Investigator

William Beaumont Army Medical Center

Fort Bliss, Texas, 79918

Recruiting
· Contact
Warren Alexander · Principal Investigator

Houston Methodist Hospital

Houston, Texas, 77030

Recruiting
· Contact
Jun Zhang · Principal Investigator

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting
· Contact
Marcelo Vailati Negrao · Principal Investigator

Lumi Research

Houston, Texas, 77090

Not Yet Recruiting
David Nguyen · Principal Investigator

USO - Texas Oncology

Webster, Texas, 77598

Recruiting
Pavel Levin · Principal Investigator

The University of Vermont Medical Center Inc.

Burlington, Vermont, 05401

Recruiting
Rohit Singh · Principal Investigator

University of Virginia Health System

Charlottesville, Virginia, 22903

Recruiting
· Contact
Ryan Gentzler · Principal Investigator

USO - Virginia Cancer Specialists

Fairfax, Virginia, 22031

Recruiting
Alexander Spira · Principal Investigator

VCU Health Adult Outpatient Pavillion

Richmond, Virginia, 23219

Recruiting
· Contact
Renato Martins · Principal Investigator

Swedish Cancer Institute - Edmonds

Edmonds, Washington, 98026

Recruiting
Siddhartha Devarakonda · Principal Investigator

Kadlec Clinic Hematology and Oncology

Kennewick, Washington, 99336

Recruiting
Ying Zhuo · Principal Investigator

Swedish Medical Center

Seattle, Washington, 98104

Recruiting
Siddhartha Devarakonda · Principal Investigator

VA Puget Sound Health Care System

Seattle, Washington, 98108

Recruiting
Daniel Wu · Principal Investigator

USO - Northwest Cancer Specialists

Vancouver, Washington, 98684

Recruiting
Anthony Van Ho · Principal Investigator

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

Madison, Wisconsin, 53715

Recruiting
Lisa Lepeak · Principal Investigator

References

  • Peters S, Hochmair M, Arbour KC, Rodriguez LP, Reck M, Leal T, R Lindsay C, Shun L, William WN, Spira AI, Sabari JK, Henning Gronberg B, Nishio M, Burns TF, Girard N, Capuzzo F, Merced A, Fasnacht N, Visseren-Grul C, Negrao MV. SUNRAY-01 trial protocol: an innovative study design of olomorasib and pembrolizumab with or without chemotherapy in KRAS G12C NSCLC. Future Oncol. 2026 Apr;22(9):1073-1082. doi: 10.1080/14796694.2026.2651961. Epub 2026 Apr 6.(PubMed)