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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
NCT06793215 · Hoffmann-La Roche
In plain English
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Official title
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
About this 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).
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
Study design
Enrollment target: 600 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-10-24
Estimated completion: 2030-10-31
Last updated: 2026-05-11
Interventions
Drug: DivarasibDrug: PembrolizumabDrug: PemetrexedDrug: CarboplatinDrug: Cisplatin
Primary outcomes
- • Progression-Free Survival (PFS) (Up to approximately 5 years)
- • Overall Survival (OS) (Up to approximately 5 years)
Sponsor
Hoffmann-La Roche · industry
With: Chugai Pharmaceutical
Contacts & investigators
ContactReference Study ID Number: CO45042 https://forpatients.roche.com/ · contact · global-roche-genentech-trials@gene.com · 888-662-6728 (U.S. and Canada)
InvestigatorClinical Trials · study_director, Hoffmann-La Roche
All locations (240)
Alaska Oncology and HematologyRecruiting
Anchorage, Alaska, United States
City of Hope - PhoenixRecruiting
Goodyear, Arizona, United States
Marin Cancer Care IncRecruiting
Greenbrae, California, United States
Hoag Memorial HospitalRecruiting
Newport Beach, California, United States
Palo Alto Medical Foundation Research CenterRecruiting
Palo Alto, California, United States
Sutter Institute for Medical ResearchRecruiting
Roseville, California, United States
California Pacific Medical CenterRecruiting
San Francisco, California, United States
Florida Cancer Specialists - SOUTH - SCRI - PPDSRecruiting
Fort Myers, Florida, United States
University of Florida Health at ShandsRecruiting
Gainesville, Florida, United States
BioResearch PartnerRecruiting
Hialeah, Florida, United States
Memorial Healthcare System - Memorial Regional HospitalRecruiting
Hollywood, Florida, United States
Sylvester Comprehensive Cancer CenterRecruiting
Miami, Florida, United States
Ascension Sacred HeartRecruiting
Pensacola, Florida, United States
Florida Cancer Specialists - NORTH - SCRI - PPDSRecruiting
St. Petersburg, Florida, United States
Florida Cancer Specialists - EAST - SCRI - PPDSRecruiting
West Palm Beach, Florida, United States
Piedmont Cancer Institute, PCRecruiting
Atlanta, Georgia, United States
City of Hope® AtlantaRecruiting
Newnan, Georgia, United States
Summit Cancer Care PCRecruiting
Savannah, Georgia, United States
St. Luke's Cancer InstituteRecruiting
Boise, Idaho, United States
Affiliated Oncologists, LLCRecruiting
Chicago Ridge, Illinois, United States
Hope and Healing Cancer ServicesWithdrawn
Hinsdale, Illinois, United States
City of Hope® Cancer Center ChicagoRecruiting
Zion, Illinois, United States
Saint Agnes Hospital - Baltimore - Hunt - PPDSRecruiting
Baltimore, Maryland, United States
Massachusetts General HospitalRecruiting
Boston, Massachusetts, United States
Profound Research, LLCRecruiting
Farmington Hills, Michigan, United States
Missouri Baptist Medical CenterRecruiting
St Louis, Missouri, United States
NHO Revive Research InstituteRecruiting
Lincoln, Nebraska, United States
San Juan Oncology AssociatesRecruiting
Farmington, New Mexico, United States
Montefiore Einstein Cancer CenterRecruiting
The Bronx, New York, United States
Clinical Research AllianceRecruiting
Westbury, New York, United States
Firsthealth of The CarolinasRecruiting
Pinehurst, North Carolina, United States
Ohio State UniversityRecruiting
Columbus, Ohio, United States
Oregon Health and Science UniversityRecruiting
Portland, Oregon, United States
St. Luke's University Health NetworkRecruiting
Bethlehem, Pennsylvania, United States
Reading Hospital - McGlinn Cancer InstituteRecruiting
West Reading, Pennsylvania, United States
Baptist Cancer CenterRecruiting
Memphis, Tennessee, United States
Renovatio Clinical - El PasoRecruiting
El Paso, Texas, United States
JPS Health NetworkRecruiting
Fort Worth, Texas, United States
The University of Texas MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
Community Clinical TrialsRecruiting
Kingwood, Texas, United States
Texas Tech Health Science CenterRecruiting
Lubbock, Texas, United States
Renovatio ClinicalRecruiting
The Woodlands, Texas, United States
University of Texas Health Center at TylerRecruiting
Tyler, Texas, United States
Virginia Oncology AssociatesRecruiting
Norfolk, Virginia, United States
Hospital Aleman de Buenos AiresRecruiting
Buenos Aires, Argentina
Hospital ItalianoRecruiting
Buenos Aires, Argentina
Hospital BritanicoRecruiting
Ciudad Autonoma Buenos Aires, Argentina
Centro Oncologico KorbenRecruiting
Ciudad Autonoma Buenos Aires, Argentina
Clinica Adventista BelgranoRecruiting
Ciudad Autonoma Buenos Aires, Argentina
Kinghorn Cancer CentreRecruiting
Darlinghurst, New South Wales, Australia
Liverpool HospitalRecruiting
Liverpool, New South Wales, Australia
Calvary Mater NewcastleRecruiting
Waratah, New South Wales, Australia
Sunshine Coast University HospitalRecruiting
Birtinya, Queensland, Australia
Royal Hobart HospitalRecruiting
Hobart, Tasmania, Australia
Monash HealthRecruiting
Clayton, Victoria, Australia
Austin HealthRecruiting
Heidelberg, Victoria, Australia
Peter Maccallum Cancer CentreRecruiting
Melbourne, Victoria, Australia
AZORG Campus Aalst-MoorselbaanRecruiting
Aalst, Belgium
UZ BrusselRecruiting
Brussels, Belgium
Cliniques Universitaires St-LucRecruiting
Brussels, Belgium
Jessa Zkh (Campus Virga Jesse)Recruiting
Hasselt, Belgium
UZ Leuven GasthuisbergRecruiting
Leuven, Belgium
CHU de Liège (Sart Tilman)Recruiting
Liège, Belgium
CHU HELORA - Hôpital de Mons - Site KennedyRecruiting
Mons, Belgium
AZ Delta (Campus Rumbeke)Recruiting
Roeselare, Belgium
Crio - Centro Regional Integrado de OncologiaRecruiting
Fortaleza, Ceará, Brazil
Centro Integrado de Oncologia de CuritibaRecruiting
Curitiba, Paraná, Brazil
Liga Norte Riograndense Contra O CâncerRecruiting
Natal, Rio Grande do Norte, Brazil
Irmandade Da Santa Casa de Misericordia de Porto AlegreRecruiting
Porto Alegre, Rio Grande do Sul, Brazil
Hospital Nossa Senhora da ConceicaoRecruiting
Porto Alegre, Rio Grande do Sul, Brazil
Fundação Pio XII Hospital de Câncer de BarretosRecruiting
Barretos, São Paulo, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESPRecruiting
São Paulo, São Paulo, Brazil
BC Cancer ? Kelowna (Sindi Ahluwalia Hawkins Centre)Recruiting
Kelowna, British Columbia, Canada
BC Cancer - VictoriaRecruiting
Victoria, British Columbia, Canada
Royal Victoria Regional Health CentreRecruiting
Barrie, Ontario, Canada
William Osler Health Centre - Brampton Civic HospitalRecruiting
Brampton, Ontario, Canada
Jewish General HospitalRecruiting
Montreal, Quebec, Canada
Centre Hospitalier Regional De RimouskiRecruiting
Rimouski, Quebec, Canada
Saskatoon Cancer CentreRecruiting
Saskatoon, Saskatchewan, Canada
CHU de Quebec - Hopital de l'Enfant-JesusRecruiting
Québec, Canada
Hunan Cancer HospitalRecruiting
Changsha, China
West China Hospital - Sichuan UniversityRecruiting
Chengdu, China
Sir Run Run Shaw Hospital Zhejiang UniversityRecruiting
Hangzhou, China
Harbin Medical University Cancer HospitalRecruiting
Harbin, China
Shanghai East HospitalRecruiting
Shanghai, China
Shanghai Pulmonary HospitalRecruiting
Shanghai, China
Aarhus UniversitetshospitalRecruiting
Aarhus N, Denmark
Herlev Hospital, Afdeling for Kræftbehandling, Center for Kræftforskning, Klinisk ForskningsenhedRecruiting
Herlev, Denmark
RigshospitaletRecruiting
København Ø, Denmark
Sjællands Universitetshospital, RoskildeRecruiting
Roskilde, Denmark
Onkologisk Ambulatorium - SønderborgRecruiting
Sønderborg, Denmark
CHU AngersRecruiting
Angers, France
Hopital AvicenneRecruiting
Bobigny, France
Hôpital Louis Pradel, Hospices Civils de LyonRecruiting
Bron, France
Centre Francois BaclesseRecruiting
Caen, France
Centre Leon BerardRecruiting
Lyon, France
CHU MontpellierRecruiting
Montpellier, France
Centre Antoine LacassagneRecruiting
Nice, France
Groupe Hospitalier Paris Saint JosephRecruiting
Paris, France
Hopital TenonRecruiting
Paris, France
CHU BordeauxRecruiting
Pessac, France
Centre Hospitalier Universitaire de ReimsRecruiting
Reims, France
CH de Saint QuentinRecruiting
Saint-Quentin, France
CHU Strasbourg - Nouvel Hopital CivilRecruiting
Strasbourg, France
Centre Hospitalier Bretagne Atlantique VannesRecruiting
Vannes, France
Vivantes - Klinikum Im Friedrichshain;Innere Medizin ? Hämatologie, Onkologie und PalliativmedizinRecruiting
Berlin, Germany
Charite - Universitätsmedizin BerlinRecruiting
Berlin, Germany
Technische Universität Dresden - Medizinische Fakultät Carl Gustav Carus;Medizinische Klinik und Poliklinik IRecruiting
Dresden, Germany
KEM/Evang. Kliniken Essen Mitte gGmbHRecruiting
Essen, Germany
Universitätsklinikum EssenRecruiting
Essen, Germany
Klinikum EsslingenRecruiting
Esslingen am Neckar, Germany
Asklepios Fachkliniken GmbHRecruiting
Gauting, Germany
Krankenhaus Martha-Maria Halle-Doelau gGmbHRecruiting
Halle, Germany
Universitätsklinikum Hamburg-EppendorfRecruiting
Hamburg, Germany
KRH Klinikum Siloah-Oststadt-HeidehausRecruiting
Hanover, Germany
Universität Des SaarlandesRecruiting
Homburg, Germany
Lungenfachklinik ImmenhausenRecruiting
Immenhausen, Germany
Vincentius-Diakonissen-Kliniken gAGRecruiting
Karlsruhe, Germany
SLK Kliniken Heilbronn GmbH, Standort Fachklinik LöwensteinRecruiting
Löwenstein, Germany
Universität MannheimRecruiting
Mannheim, Germany
Pius Hospital OldenburgRecruiting
Oldenburg, Germany
Universitätsklinikum RegensburgRecruiting
Regensburg, Germany
Klinikum Würzburg Mitte gGmbHRecruiting
Würzburg, Germany
Sotiria General Hospital of AthensRecruiting
Athens, Greece
Alexandras HospitalRecruiting
Athens, Greece
Errikos Dynan HospitalRecruiting
Athens, Greece
University Hospital of LarissaRecruiting
Larissa, Greece
Interbalkan Medical Center of ThessalonikiRecruiting
Thessaloniki, Greece
Theageneion Anticancer HospitalRecruiting
Thessaloniki, Greece
Ag. Loukas HospitalRecruiting
Thessaloniki, Greece
Queen Mary HospitalRecruiting
Hong Kong, Hong Kong
Tuen Mun HospitalRecruiting
Hong Kong, Hong Kong
Queen Elizabeth Hospital Department of Clinical OncologyRecruiting
Kowloon, Hong Kong
Prince of Wales HospRecruiting
Shatin, Hong Kong
Matrai GyogyintezetRecruiting
Mátraháza, Hungary
Pécsi TudományegyetemRecruiting
Pécs, Hungary
Református Pulmonológiai CentrumRecruiting
Törökbálint, Hungary
St James HospitalRecruiting
Dublin, Ireland
Beaumont HospitalRecruiting
Dublin, Ireland
Tallaght HospitalRecruiting
Dublin, Ireland
Mater Misecordiae University HospitalRecruiting
Dublin, Ireland
Ospedale Giuseppe MoscatiRecruiting
Statte, Apulia, Italy
AORN Ospedali dei Colli Ospedale MonaldiRecruiting
Naples, Campania, Italy
Istituto Nazionale Tumori Fondazione G. PascaleRecruiting
Naples, Campania, Italy
A.O. Universitaria Policlinico Di ModenaRecruiting
Modena, Emilia-Romagna, Italy
Presidio san salvatore muragliaRecruiting
Pesaro, Emilia-Romagna, Italy
Irccs Centro Di Riferimento Oncologico (CRO)Recruiting
Aviano, Friuli Venezia Giulia, Italy
Azienda Ospedaliera San Camillo ForlaniniRecruiting
Rome, Lazio, Italy
Policlinico Universitario "Agostino Gemelli"Recruiting
Rome, Lazio, Italy
IEO Istituto Europeo di OncologiaRecruiting
Milan, Lombardy, Italy
Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda)Recruiting
Milan, Lombardy, Italy
Azienda Ospedaliera San Gerardo di MonzaRecruiting
Monza MI, Lombardy, Italy
Humanitas Centro Catanese Di OncologiaRecruiting
Misterbianco (CT), Sicily, Italy
USL 6 Toscana Nord Ovest ? P.O. LivornoRecruiting
Livorno, Tuscany, Italy
Ospedale P. Pederzoli Casa di cura PrivataRecruiting
Peschiera Del Garda (VR), Veneto, Italy
Kyushu University HospitalRecruiting
Fukuoka, Japan
Kurume University HospitalRecruiting
Fukuoka, Japan
Hakodate Goryoukaku HospitalRecruiting
Hokkaido, Japan
Hyogo Medical University HospitalRecruiting
Hyōgo, Japan
Kagoshima University HospitalRecruiting
Kagoshima, Japan
Kanagawa Cancer CenterRecruiting
Kanagawa, Japan
Sendai Kousei HospitalRecruiting
Miyagi, Japan
Niigata University Medical & Dental HospitalRecruiting
Niigata, Japan
Okayama University HospitalRecruiting
Okayama, Japan
Osaka Metropolitan University HospitalRecruiting
Osaka, Japan
Kansai Medical University HospitalRecruiting
Osaka, Japan
Tohoku University HospitalRecruiting
Sendai, Japan
Juntendo University HospitalRecruiting
Tokyo, Japan
The Cancer Institute Hospital of JFCRRecruiting
Tokyo, Japan
Tokyo Medical University HospitalRecruiting
Tokyo, Japan
Wakayama Medical University HospitalRecruiting
Wakayama, Japan
Hospital Civil de Guadalajara Fray Antonio AlcaldeRecruiting
Guadalajara, Jalisco, Mexico
ARKE Estudios Clínicos S.A. de C.V.Recruiting
Mexico City, Mexico
Meander Medisch CentrumRecruiting
Amersfoort, Utrecht, Netherlands
Ziekenhuis RijnstateRecruiting
Arnhem, Netherlands
Amphia ZiekenhuisRecruiting
Breda, Netherlands
Ziekenhuis St. JansdalRecruiting
Harderwijk, Netherlands
IsalaRecruiting
Zwolle, Netherlands
Harbour Cancer and WellnessRecruiting
Auckland, New Zealand
Wellington HospitalRecruiting
Newtown, New Zealand
Centrum Pulmonologii i TorakochirurgiiRecruiting
Bystra, Poland
Uniwersyteckie Centrum KliniczneRecruiting
Gda?sk, Poland
Krakowski Szpital Specjalistyczny im sw.Jana Pawla IIRecruiting
Krakow, Poland
Uniwersytecki Szpital Kliniczny nr 4 w LublinieRecruiting
Lublin, Poland
Warminsko-Mazurskie Centrum Chorób P?uc w OlsztynieRecruiting
Olsztyn, Poland
Wielkopolskie Centrum Pulmonologii i Torakochirurgii w PoznaniuRecruiting
Poznan, Poland
Radomskie Centrum OnkologiiRecruiting
Radom, Poland
Instytut Gruzlicy I Chorob PlucRecruiting
Warsaw, Poland
Mazowiecki Szpital OnkologicznyRecruiting
Wieliszew, Poland
Dolnoslaskie Centrum Chorob PlucRecruiting
Wroclaw, Poland
Hospital de BragaRecruiting
Braga, Portugal
Hospital Beatriz AngeloRecruiting
Loures, Portugal
IPO do PortoRecruiting
Porto, Portugal
CHVNG/E_Unidade 1Recruiting
Vila Nova de Gaia, Portugal
National University HospitalRecruiting
Singapore, Singapore
National Cancer CentreRecruiting
Singapore, Singapore
Wits Donald Gordon Clinical Trial CentreRecruiting
Parktown, South Africa
Chris Hani Baragwanath Clinical Trial SiteRecruiting
Soweto, South Africa
Pusan National University HospitalRecruiting
Busan, South Korea
Chungbuk National University HospitalRecruiting
Cheongju-si, South Korea
Kyungpook National University Chilgok HospitalRecruiting
Daegu, South Korea
The Catholic University of Korea, Seoul St. Mary's HospitalRecruiting
Seoul, South Korea
Seoul National University HospitalRecruiting
Seoul, South Korea
Korea University Guro HospitalRecruiting
Seoul, South Korea
Hospital Universitario Son EspasesRecruiting
Palma de Mallorca, Balearic Islands, Spain
Hospital Universitario Marques de ValdecillaRecruiting
Santander, Cantabria, Spain
Complejo Hospitalario Universitario Insular?Materno InfantilRecruiting
Las Palmas de Gran Canaria, LAS Palmas, Spain
Clinica Universitaria de NavarraRecruiting
Pamplona, Navarre, Spain
Hospital Universitari Vall d HebronRecruiting
Barcelona, Spain
Hospital Clinic BarcelonaRecruiting
Barcelona, Spain
Hospital de la Santa Creu i Sant PauRecruiting
Barcelona, Spain
Clinica Universidad de Navarra MadridRecruiting
Madrid, Spain
Hospital Ramon y CajalRecruiting
Madrid, Spain
Hospital Universitario 12 de OctubreRecruiting
Madrid, Spain
Hospital Universitario La PazRecruiting
Madrid, Spain
Hospital Clinico Universitario Virgen de la VictoriaRecruiting
Málaga, Spain
Hospital Universitario Virgen MacarenaRecruiting
Seville, Spain
Hospital Clínico Universitario de ValenciaRecruiting
Valencia, Spain
Kantonsspital BadenRecruiting
Baden, Switzerland
Universitaetsspital BaselRecruiting
Basel, Switzerland
Kantonsspital Graubünden Medizin OnkologieRecruiting
Chur, Switzerland
Hôpital Universitaire de Genève (HUG)Recruiting
Geneva, Switzerland
Kaohsiung Medical University Chung-Ho Memorial HospitalRecruiting
Kaohsiung City, Taiwan
E-DA HospitalRecruiting
Kaohsiung City, Taiwan
Chung Shan Medical University HospitalRecruiting
Taichung, Taiwan
National Taiwan University HospitalRecruiting
Taipei, Taiwan
Taipei Medical University HospitalRecruiting
Taipei, Taiwan
Taipei Veterans General HospitalRecruiting
Taipei, Taiwan
National Taiwan University Cancer CenterRecruiting
Zhongzheng Dist., Taiwan
Blackpool Teaching Hospitals NHS Foundation Trust , Victoria HospitalRecruiting
Blackpool, United Kingdom
Bristol Haematology & Oncology CentreRecruiting
Bristol, United Kingdom
East Kent Hospitals University NHS Foundation TrustRecruiting
Canterbury, United Kingdom
Velindre NHS Trust - Velindre Cancer CentreRecruiting
Cardiff, United Kingdom
Hull University Teaching Hospitals NHS TrustRecruiting
Hull, United Kingdom
Barts and the London NHS TrustRecruiting
London, United Kingdom
Royal Marsden Hospital - FulhamRecruiting
London, United Kingdom
Sarah Cannon Research InstituteRecruiting
London, United Kingdom
Maidstone and Tunbridge Wells NHS TrustRecruiting
Maidstone, United Kingdom
Oxford University Hospitals NHS Trust - Churchill HospitalRecruiting
Oxford, United Kingdom
Royal Marsden NHS Foundation TrustRecruiting
Sutton, United Kingdom