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

NCT ID: NCT06793215

Last Updated: 2025-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

600 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-10-24

Study Completion Date

2030-10-31

Brief Summary

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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).

Detailed Description

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Conditions

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Non-Small Cell Lung Cancer KRAS G12C Lung Cancer

Keywords

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Divarasib + Pembrolizumab

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

Group Type EXPERIMENTAL

Divarasib

Intervention Type DRUG

Divarasib will be administered orally QD

Pembrolizumab

Intervention Type DRUG

Pembrolizumab will be administered via IV infusion Q3W

Pembrolizumab + Pemetrexed + Carboplatin or Cisplatin

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

Group Type ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type DRUG

Pembrolizumab will be administered via IV infusion Q3W

Pemetrexed

Intervention Type DRUG

Pemetrexed will be administered via IV infusion Q3W

Carboplatin

Intervention Type DRUG

Carboplatin will be administered via IV infusion Q3W

Cisplatin

Intervention Type DRUG

Cisplatin will be administered via IV infusion Q3W

Interventions

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Divarasib

Divarasib will be administered orally QD

Intervention Type DRUG

Pembrolizumab

Pembrolizumab will be administered via IV infusion Q3W

Intervention Type DRUG

Pemetrexed

Pemetrexed will be administered via IV infusion Q3W

Intervention Type DRUG

Carboplatin

Carboplatin will be administered via IV infusion Q3W

Intervention Type DRUG

Cisplatin

Cisplatin will be administered via IV infusion Q3W

Intervention Type DRUG

Eligibility Criteria

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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

* 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)


* 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


* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Chugai Pharmaceutical

INDUSTRY

Sponsor Role collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Alaska Oncology and Hematology

Anchorage, Alaska, United States

Site Status RECRUITING

Marin Cancer Care Inc

Greenbrae, California, United States

Site Status RECRUITING

BioResearch Partner

Hialeah, Florida, United States

Site Status RECRUITING

Piedmont Cancer Institute, PC

Atlanta, Georgia, United States

Site Status RECRUITING

Summit Cancer Care PC

Savannah, Georgia, United States

Site Status RECRUITING

St. Luke's Cancer Institute

Boise, Idaho, United States

Site Status RECRUITING

Hope and Healing Cancer Services

Hinsdale, Illinois, United States

Site Status RECRUITING

Profound Research, LLC

Farmington Hills, Michigan, United States

Site Status RECRUITING

Missouri Baptist Medical Center

St Louis, Missouri, United States

Site Status RECRUITING

San Juan Oncology Associates

Farmington, New Mexico, United States

Site Status RECRUITING

Clinical Research Alliance

Westbury, New York, United States

Site Status RECRUITING

Baptist Cancer Center

Memphis, Tennessee, United States

Site Status RECRUITING

Renovatio Clinical - El Paso

El Paso, Texas, United States

Site Status RECRUITING

JPS Health Network

Fort Worth, Texas, United States

Site Status RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Community Clinical Trials

Kingwood, Texas, United States

Site Status RECRUITING

Texas Tech Health Science Center

Lubbock, Texas, United States

Site Status RECRUITING

Renovatio Clinical

The Woodlands, Texas, United States

Site Status RECRUITING

University of Texas Health Center at Tyler

Tyler, Texas, United States

Site Status RECRUITING

Kinghorn Cancer Centre

Darlinghurst, New South Wales, Australia

Site Status RECRUITING

Calvary Mater Newcastle

Warath, New South Wales, Australia

Site Status RECRUITING

Sunshine Coast University Hospital

Birtinya, Queensland, Australia

Site Status RECRUITING

Monash Health

Clayton, Victoria, Australia

Site Status RECRUITING

Austin Health

Heidelberg, Victoria, Australia

Site Status RECRUITING

Peter Maccallum Cancer Centre

Melbourne, Victoria, Australia

Site Status RECRUITING

Jessa Zkh (Campus Virga Jesse)

Hasselt, , Belgium

Site Status RECRUITING

Crio - Centro Regional Integrado de Oncologia

Fortaleza, Ceará, Brazil

Site Status RECRUITING

Centro Integrado de Oncologia de Curitiba

Curitiba, Paraná, Brazil

Site Status RECRUITING

Liga Norte Riograndense Contra O Câncer

Natal, Rio Grande do Norte, Brazil

Site Status RECRUITING

Irmandade Da Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Site Status RECRUITING

Fundação Pio XII Hospital de Câncer de Barretos

Barretos, São Paulo, Brazil

Site Status RECRUITING

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, Brazil

Site Status RECRUITING

Royal Victoria Regional Health Centre

Barrie, Ontario, Canada

Site Status RECRUITING

Centre Hospitalier Regional De Rimouski

Rimouski, Quebec, Canada

Site Status RECRUITING

Sir Run Run Shaw Hospital Zhejiang University

Hangzhou, , China

Site Status RECRUITING

Shanghai Pulmonary Hospital

Shanghai, , China

Site Status RECRUITING

Shanghai East Hospital

Shanghai, , China

Site Status RECRUITING

Aarhus Universitetshospital

Aarhus N, , Denmark

Site Status RECRUITING

Sjællands Universitetshospital, Roskilde

Roskilde, , Denmark

Site Status RECRUITING

CHU Montpellier

Montpellier, , France

Site Status RECRUITING

Groupe Hospitalier Paris Saint Joseph

Paris, , France

Site Status RECRUITING

CH de Saint Quentin

Saint-Quentin, , France

Site Status RECRUITING

Centre Hospitalier Bretagne Atlantique Vannes

Vannes, , France

Site Status RECRUITING

Vivantes - Klinikum Im Friedrichshain;Innere Medizin ? Hämatologie, Onkologie und Palliativmedizin

Berlin, , Germany

Site Status RECRUITING

Charite - Universitätsmedizin Berlin

Berlin, , Germany

Site Status RECRUITING

Technische Universität Dresden - Medizinische Fakultät Carl Gustav Carus;Medizinische Klinik und Poliklinik I

Dresden, , Germany

Site Status RECRUITING

Universitätsklinikum Essen

Essen, , Germany

Site Status RECRUITING

Klinikum Esslingen

Esslingen am Neckar, , Germany

Site Status RECRUITING

Krankenhaus Martha-Maria Halle-Doelau gGmbH

Halle, , Germany

Site Status RECRUITING

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Site Status RECRUITING

KRH Klinikum Siloah-Oststadt-Heidehaus

Hanover, , Germany

Site Status RECRUITING

Universität Des Saarlandes

Homburg, , Germany

Site Status RECRUITING

Lungenfachklinik Immenhausen

Immenhausen, , Germany

Site Status RECRUITING

Vincentius-Diakonissen-Kliniken gAG

Karlsruhe, , Germany

Site Status RECRUITING

SLK Kliniken Heilbronn GmbH, Standort Fachklinik Löwenstein

Löwenstein, , Germany

Site Status RECRUITING

Universität Mannheim

Mannheim, , Germany

Site Status RECRUITING

Universitätsklinikum Regensburg

Regensburg, , Germany

Site Status RECRUITING

Queen Mary Hospital

Hong Kong, , Hong Kong

Site Status RECRUITING

Tuen Mun Hospital

Hong Kong, , Hong Kong

Site Status RECRUITING

Queen Elizabeth Hospital Department of Clinical Oncology

Kowloon, , Hong Kong

Site Status RECRUITING

Prince of Wales Hosp

Shatin, , Hong Kong

Site Status RECRUITING

Matrai Gyogyintezet

Mátraháza, , Hungary

Site Status RECRUITING

Reformatus Pulmonologiai Centrum

Törökbálint, , Hungary

Site Status RECRUITING

Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, Campania, Italy

Site Status RECRUITING

USL 6 Toscana Nord Ovest ? P.O. Livorno

Livorno, Tuscany, Italy

Site Status RECRUITING

Ospedale P. Pederzoli Casa di cura Privata

Peschiera Del Garda (VR), Veneto, Italy

Site Status RECRUITING

Amphia Ziekenhuis

Breda, , Netherlands

Site Status RECRUITING

Ziekenhuis St. Jansdal

Harderwijk, , Netherlands

Site Status RECRUITING

Harbour Cancer and Wellness

Auckland, , New Zealand

Site Status RECRUITING

Centrum Pulmonologii i Torakochirurgii

Bystra, , Poland

Site Status RECRUITING

Uniwersyteckie Centrum Kliniczne

Gda?sk, , Poland

Site Status RECRUITING

Krakowski Szpital Specjalistyczny im sw.Jana Pawla II

Krakow, , Poland

Site Status RECRUITING

Uniwersytecki Szpital Kliniczny nr 4 w Lublinie

Lublin, , Poland

Site Status RECRUITING

Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie

Olsztyn, , Poland

Site Status RECRUITING

Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu

Poznan, , Poland

Site Status RECRUITING

Instytut Gruzlicy I Chorob Pluc

Warsaw, , Poland

Site Status RECRUITING

Mazowiecki Szpital Onkologiczny

Wieliszew, , Poland

Site Status RECRUITING

Dolnoslaskie Centrum Chorob Pluc

Wroclaw, , Poland

Site Status RECRUITING

Hospital de Braga

Braga, , Portugal

Site Status RECRUITING

Hospital Beatriz Angelo

Loures, , Portugal

Site Status RECRUITING

IPO do Porto

Porto, , Portugal

Site Status RECRUITING

CHVNG/E_Unidade 1

Vila Nova de Gaia, , Portugal

Site Status RECRUITING

National University Hospital

Singapore, , Singapore

Site Status RECRUITING

National Cancer Centre

Singapore, , Singapore

Site Status RECRUITING

Pusan National University Hospital

Busan, , South Korea

Site Status RECRUITING

Chungbuk National University Hospital

Cheongju-si, , South Korea

Site Status RECRUITING

Kyungpook National University Chilgok Hospital

Daegu, , South Korea

Site Status RECRUITING

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, , South Korea

Site Status RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status RECRUITING

Korea University Guro Hospital

Seoul, , South Korea

Site Status RECRUITING

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, Spain

Site Status RECRUITING

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, Spain

Site Status RECRUITING

Clinica Universitaria de Navarra

Pamplona, Navarre, Spain

Site Status RECRUITING

Hospital Universitario La Paz

Madrid, , Spain

Site Status RECRUITING

Hospital Clinico Universitario Virgen de la Victoria

Málaga, , Spain

Site Status RECRUITING

Kantonsspital Graubünden Medizin Onkologie

Chur, , Switzerland

Site Status RECRUITING

Hôpital Universitaire de Genève (HUG)

Geneva, , Switzerland

Site Status RECRUITING

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Site Status RECRUITING

E-DA Hospital

Kaohsiung City, , Taiwan

Site Status RECRUITING

Chung Shan Medical University Hospital

Taichung, , Taiwan

Site Status RECRUITING

Taipei Medical University Hospital

Taipei, , Taiwan

Site Status RECRUITING

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status RECRUITING

Bristol Haematology & Oncology Centre

Bristol, , United Kingdom

Site Status RECRUITING

East Kent Hospitals University NHS Foundation Trust

Canterbury, , United Kingdom

Site Status RECRUITING

Barts and the London NHS Trust

London, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Belgium Brazil Canada China Denmark France Germany Hong Kong Hungary Italy Netherlands New Zealand Poland Portugal Singapore South Korea Spain Switzerland Taiwan United Kingdom

Central Contacts

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Reference Study ID Number: CO45042 https://forpatients.roche.com/

Role: CONTACT

Phone: 888-662-6728 (U.S. and Canada)

Email: [email protected]

Other Identifiers

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CO45042

Identifier Type: -

Identifier Source: org_study_id