Recruiting
Phase 3

Divarasib & Pembrolizumab

Sponsor:

Hoffmann-La Roche

Code:

NCT06793215

Conditions

Non-Small Cell Lung Cancer

KRAS G12C Lung Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Divarasib

Pembrolizumab

Pemetrexed

Carboplatin

Cisplatin

Study Details

Brief summary:

The purpose of this study is to evaluate the efficacy and safety of divarasib and pembrolizumab compared with pembrolizumab and pemetrexed and carboplatin or cisplatin, for the first-line treatment of adult participants with KRAS G12C-mutated, advanced or metastatic non squamous non-small cell lung cancer (NSCLC).

Conditions

Non-Small Cell Lung Cancer

KRAS G12C Lung Cancer

Study ID

NCT06793215

Start date

Oct 24, 2025

Status verified date

Aug, 2026

Completion date

Oct 31, 2030

Anticipated

Primary completion date

Nov 30, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Histologically or cytologically confirmed diagnosis of advanced or metastatic non squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy
  • Measurable disease, as defined by RECIST v1.1
  • No prior systemic treatment for advanced or metastatic NSCLC
  • Documentation of the presence of a KRAS G12C mutation
  • Documentation of known PD-L1 expression status in tumor tissue
  • Availability of a representative tumor specimen
  • Adequate end-organ function
  • Eligible to receive a platinum-based chemotherapy regimen

Exclusion Criteria Related to NSCLC:

  • Known concomitant second oncogenic driver with available targeted treatment
  • Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
  • Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >=2 weeks prior to randomization
  • History of leptomeningeal disease
  • Uncontrolled tumor-related pain
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once a month or more frequently)

Exclusion Criteria Related to Current or Prior Treatments:

  • Any anti-cancer systemic therapy, including hormonal therapy, within 21 days prior to randomization, or is expected to require any other form of antineoplastic therapy while in the study
  • Radiation therapy including palliative RT to bone metastases within 2 weeks prior to randomization and RT to the lung >30Gy within 6 months prior to randomization
  • Prior treatment with KRAS G12C inhibitors or pan-KRAS/RAS inhibitors
  • Treatment with systemic immunosuppressive or immunostimulatory medications, including CD137 agonists and immune checkpoint inhibitors
  • Current treatment with medications that are well known to prolong the QT interval
  • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to randomization
  • Prior allogeneic stem cell or solid organ transplantation

Exclusion Criteria Related to General Health:

  • History of malignancy other than NSCLC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival \[OS\] rate >90%), such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, localized prostate cancer, ductal breast carcinoma in situ, or Stage I uterine cancer
  • Individuals with chronic diarrhea, short bowel syndrome or significant upper gastrointestinal surgery including gastric resection, a history of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) or any active bowel inflammation (including diverticulitis), malabsorption syndrome, conditions that would interfere with enteral absorption
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on the screening chest computed tomography scan
  • Significant cardiovascular disease within 3 months prior to screening

Study Design

Enrollment

600 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Divarasib + Pembrolizumab

Participants will receive divarasib orally, once daily (QD) and pembrolizumab via intravenous (IV) infusion every 3 weeks (Q3W)

active comparator: Pembrolizumab + Pemetrexed + Carboplatin or Cisplatin

Participants will receive pembrolizumab, pemetrexed and carboplatin or cisplatin via IV infusion Q3W

Interventions

Divarasib

Divarasib will be administered orally QD

Pembrolizumab

Pembrolizumab will be administered via IV infusion Q3W

Pemetrexed

Pemetrexed will be administered via IV infusion Q3W

Carboplatin

Carboplatin will be administered via IV infusion Q3W

Cisplatin

Cisplatin will be administered via IV infusion Q3W

Primary outcome measure

  • Progression-Free Survival (PFS) [ Time Frame: Up to approximately 5 years ]
  • Overall Survival (OS) [ Time Frame: Up to approximately 5 years ]

Central Contacts and Locations

Central contacts

Reference Study ID Number: CO45042 https://forpatients.roche.com/ No attachments to email below.

888-662-6728 (U.S. and Canada)global-roche-genentech-trials@gene.com

Locations

Alaska Oncology and Hematology

Recruiting

Anchorage, Alaska, United States, 99508

City of Hope - Phoenix

Recruiting

Goodyear, Arizona, United States, 85338

Community Cancer Institute (CCI)

Recruiting

Clovis, California, United States, 93611

Marin Cancer Care Inc

Recruiting

Greenbrae, California, United States, 94904

UCLA Oncology Center

Recruiting

Los Angeles, California, United States, 90024

Hoag Memorial Hospital

Recruiting

Newport Beach, California, United States, 92658

Palo Alto Medical Foundation Research Center

Recruiting

Palo Alto, California, United States, 94301

Sutter Institute for Medical Research

Recruiting

Roseville, California, United States, 95661

California Pacific Medical Center

Recruiting

San Francisco, California, United States, 94115

UC Health Oncology Research

Recruiting

Colorado Springs, Colorado, United States, 80909

Poudre Valley Health Care, Inc. d/b/a Poudre Valley Health System

Recruiting

Fort Collins, Colorado, United States, 80528

Hartford Hospital

Recruiting

Hartford, Connecticut, United States, 06102-5037

Florida Cancer Specialists - SOUTH - SCRI - PPDS

Recruiting

Fort Myers, Florida, United States, 33901-8108

University of Florida Health at Shands

Recruiting

Gainesville, Florida, United States, 32610

BioResearch Partner

Recruiting

Hialeah, Florida, United States, 33013

Memorial Healthcare System - Memorial Regional Hospital

Recruiting

Hollywood, Florida, United States, 33021

Sylvester Comprehensive Cancer Center

Recruiting

Miami, Florida, United States, 33136

Ascension Sacred Heart

Recruiting

Pensacola, Florida, United States, 32504

Florida Cancer Specialists - NORTH - SCRI - PPDS

Recruiting

St. Petersburg, Florida, United States, 33701

Florida Cancer Specialists - EAST - SCRI - PPDS

Recruiting

West Palm Beach, Florida, United States, 33401-3406

Piedmont Cancer Institute, PC

Recruiting

Atlanta, Georgia, United States, 30318

City of Hope® Atlanta

Recruiting

Newnan, Georgia, United States, 30265

Summit Cancer Care PC

Recruiting

Savannah, Georgia, United States, 31405

St. Luke's Cancer Institute

Recruiting

Boise, Idaho, United States, 83712

Affiliated Oncologists, LLC

Recruiting

Chicago Ridge, Illinois, United States, 60415

City of Hope® Cancer Center Chicago

Recruiting

Zion, Illinois, United States, 60099

Mission Cancer + Blood - IMMC

Recruiting

Des Moines, Iowa, United States, 50309

University of Iowa

Recruiting

Iowa City, Iowa, United States, 52242

Saint Agnes Hospital - Baltimore - Hunt - PPDS

Recruiting

Baltimore, Maryland, United States, 21229-5201

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Profound Research, LLC

Recruiting

Farmington Hills, Michigan, United States, 48334

Missouri Baptist Medical Center

Recruiting

St Louis, Missouri, United States, 63131

NHO Revive Research Institute

Recruiting

Lincoln, Nebraska, United States, 68506

Cancer Care Specialists

Recruiting

Reno, Nevada, United States, 89511

San Juan Oncology Associates

Recruiting

Farmington, New Mexico, United States, 87401

SUNY Upstate Medical University

Recruiting

Syracuse, New York, United States, 13210

Montefiore Einstein Cancer Center

Recruiting

The Bronx, New York, United States, 10461

Clinical Research Alliance

Recruiting

Westbury, New York, United States, 11590

Firsthealth of The Carolinas

Recruiting

Pinehurst, North Carolina, United States, 28374

Ohio State University

Recruiting

Columbus, Ohio, United States, 43210

Oregon Health and Science University

Recruiting

Portland, Oregon, United States, 97239

St. Luke's University Health Network

Recruiting

Bethlehem, Pennsylvania, United States, 18015

Allegheny Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15212

Reading Hospital - McGlinn Cancer Institute

Recruiting

West Reading, Pennsylvania, United States, 19611

Baptist Cancer Center

Recruiting

Memphis, Tennessee, United States, 38120

The University of Texas Southwestern Medical Center at Dallas

Recruiting

Dallas, Texas, United States, 75390-8575

Renovatio Clinical - El Paso

Recruiting

El Paso, Texas, United States, 79915

JPS Health Network

Recruiting

Fort Worth, Texas, United States, 76104

The University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030-4000

Community Clinical Trials

Recruiting

Kingwood, Texas, United States, 77339

Texas Tech Health Science Center

Recruiting

Lubbock, Texas, United States, 79415

Renovatio Clinical

Recruiting

The Woodlands, Texas, United States, 77380

University of Texas Health Center at Tyler

Recruiting

Tyler, Texas, United States, 75708

Virginia Oncology Associates

Recruiting

Norfolk, Virginia, United States, 23502

BC Cancer ? Kelowna (Sindi Ahluwalia Hawkins Centre)

Recruiting

Kelowna, British Columbia, Canada, V1Y 5L3

BC Cancer - Victoria

Recruiting

Victoria, British Columbia, Canada, V8R 6V5

Royal Victoria Regional Health Centre

Recruiting

Barrie, Ontario, Canada, L4M 6M2

William Osler Health Centre - Brampton Civic Hospital

Recruiting

Brampton, Ontario, Canada, L6R 3J7

Ottawa Hospital Research Institute

Recruiting

Ottawa, Ontario, Canada, K1H 8L6

Jewish General Hospital

Recruiting

Montreal, Quebec, Canada, H3T 1E2

Centre Hospitalier Regional De Rimouski

Recruiting

Rimouski, Quebec, Canada, G5L 5T1

Saskatoon Cancer Centre

Recruiting

Saskatoon, Saskatchewan, Canada, S7N 4H4

CHU de Quebec - Hopital de l'Enfant-Jesus

Recruiting

Québec, Canada, G1J 1Z4

More Information

Sponsor

Hoffmann-La Roche

Last update posted

Aug 6, 2026

Last verified

Aug, 2026

Keywords

  • Advanced Non-Small Cell Lung Cancer
  • KRAS G12 Lung Cancer
  • Advanced Lung Cancer
  • Metastatic lung cancer
  • Divarasib
  • KRAS G12C Inhibitor
  • KRAS G12C Positive
  • KRAS Mutation
  • KRAS G12C Mutation
  • Lung Cancer Mutation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-03. This information was provided to ClinicalTrials.gov by Hoffmann-La Roche on 2026-08-06.