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A Study Evaluating the Efficacy and Safety of Divarasib and Pembrolizumab Versus Pembrolizumab and Pemetrexed and Carboplatin or Cisplatin in Participants With Previously Untreated, KRAS G12C-Mutated, Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer

RecruitingPhase 3

A Phase III, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Divarasib and Pembrolizumab Versus Pembrolizumab and Pemetrexed and Carboplatin or Cisplatin in Patients With Previously Untreated, KRAS G12C-Mutated, Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer

Who can join

Ages 18 and older · All sexes

Full eligibility criteria
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

About the study

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).

What is being tested

Sponsor: Hoffmann-La Roche · Participants: 600 · Started: Oct 24, 2025

Contact the study team

Official record on ClinicalTrials.gov — NCT06793215

Locations in the U.S.

AlaskaAlaska Oncology and Hematology, Anchorage
ArizonaCity of Hope - Phoenix, Goodyear
CaliforniaCommunity Cancer Institute (CCI), Clovis
Marin Cancer Care Inc, Greenbrae
UCI Health-CIACC, Irvine
UCLA Oncology Center, Los Angeles
Hoag Memorial Hospital, Newport Beach
University of California Irvine, Orange
Palo Alto Medical Foundation Research Center, Palo Alto
Sutter Institute for Medical Research, Roseville
California Pacific Medical Center, San Francisco
ColoradoUC Health Oncology Research, Colorado Springs
Poudre Valley Health Care, Inc. d/b/a Poudre Valley Health System, Fort Collins
ConnecticutHartford Hospital, Hartford
FloridaFlorida Cancer Specialists - SOUTH - SCRI - PPDS, Fort Myers
University of Florida Health at Shands, Gainesville
BioResearch Partner, Hialeah
Memorial Healthcare System - Memorial Regional Hospital, Hollywood
Sylvester Comprehensive Cancer Center, Miami
Ascension Sacred Heart, Pensacola
Florida Cancer Specialists - NORTH - SCRI - PPDS, St. Petersburg
Florida Cancer Specialists - EAST - SCRI - PPDS, West Palm Beach
GeorgiaPiedmont Cancer Institute, PC, Atlanta
City of Hope® Atlanta, Newnan
Summit Cancer Care PC, Savannah
IdahoSt. Luke's Cancer Institute, Boise
IllinoisAffiliated Oncologists, LLC, Chicago Ridge
City of Hope® Cancer Center Chicago, Zion
IowaMission Cancer + Blood - IMMC, Des Moines
University of Iowa, Iowa City
MarylandSaint Agnes Hospital - Baltimore - Hunt - PPDS, Baltimore
Walter Reed National Military Medical Center, Bethesda
MassachusettsMassachusetts General Hospital, Boston
University of Massachusetts Memorial Medical Center, Worcester
MichiganProfound Research, LLC, Farmington Hills
MissouriMissouri Baptist Medical Center, St Louis
NebraskaNHO Revive Research Institute, Lincoln
NevadaCancer Care Specialists, Reno
New MexicoSan Juan Oncology Associates, Farmington
New YorkSUNY Upstate Medical University, Syracuse
Montefiore Einstein Cancer Center, The Bronx
Clinical Research Alliance, Westbury
North CarolinaFirsthealth of The Carolinas, Pinehurst
OhioOhio State University, Columbus
OregonOregon Health and Science University, Portland
PennsylvaniaSt. Luke's University Health Network, Bethlehem
Allegheny Cancer Center, Pittsburgh
Reading Hospital - McGlinn Cancer Institute, West Reading
TennesseeBaptist Cancer Center, Memphis
TexasThe University of Texas Southwestern Medical Center at Dallas, Dallas
Renovatio Clinical - El Paso, El Paso
JPS Health Network, Fort Worth
The University of Texas MD Anderson Cancer Center, Houston
Community Clinical Trials, Kingwood
Texas Tech Health Science Center, Lubbock
Renovatio Clinical, The Woodlands
University of Texas Health Center at Tyler, Tyler
VirginiaVirginia Oncology Associates, Norfolk
WisconsinAscension Network - St Elizabeth's Hospital, Appleton
Ascension Columbia St. Mary's, Milwaukee

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.