A Study Evaluating the Efficacy and Safety of Divarasib Versus Sotorasib or Adagrasib in Participants With Previously Treated KRAS G12C-positive Advanced or Metastatic Non-Small Cell Lung Cancer

NCT ID: NCT06497556

Last Updated: 2026-01-20

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

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

338 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-09-23

Study Completion Date

2029-11-30

Brief Summary

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The purpose of this study is to assess the safety and efficacy of divarasib compared to locally approved KRAS G12C inhibitors (sotorasib or adagrasib) in participants with KRAS G12C-positive (KRAS G12C +) advanced or metastatic 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

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

Participants will receive divarasib orally, once daily (QD).

Group Type EXPERIMENTAL

Divarasib

Intervention Type DRUG

Divarasib will be administered orally QD

KRAS G12C inhibitor

Participants will receive sotorasib orally QD or adagrasib orally twice a day (BID)

Group Type ACTIVE_COMPARATOR

Sotorasib

Intervention Type DRUG

Sotorasib will be administered orally QD

Adagrasib

Intervention Type DRUG

Adagrasib will be administred orally BID

Interventions

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Divarasib

Divarasib will be administered orally QD

Intervention Type DRUG

Sotorasib

Sotorasib will be administered orally QD

Intervention Type DRUG

Adagrasib

Adagrasib will be administred orally BID

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Unequivocal histologically or cytologically confirmed diagnosis of metastatic or locally advanced NSCLC not amenable to treatment with surgical resection or combined chemoradiation
* Disease progression during or after treatment with at least one prior systemic therapy but no more than three lines of prior systemic therapy in the advanced or metastatic setting
* Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
* Documentation of the presence of a KRAS G12C mutation
* Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or 10-15 (15 preferred) unstained, freshly cut, serial slides with an associated pathology report
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy of \>= 12 weeks

Exclusion Criteria

* Known hypersensitivity to any of the components of divarasib, or sotorasib or adagrasib
* Malabsorption syndrome or other condition that would interfere with enteral absorption
* Known concomitant second oncogenic driver
* Mixed small-cell lung cancer or large cell neuroendocrine histology
* Known and untreated, or active central nervous system (CNS) metastases
* Leptomeningeal disease or carcinomatous meningitis
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures biweekly or more frequently
* Any infection that, in the opinion of the investigator, could impact patient safety, or treatment with therapeutic oral or IV antibiotics within 14 days prior to Day 1 of Cycle 1
* Prior treatment with any KRAS G12C inhibitor or pan-KRAS/RAS inhibitor
* More than 30 Gy of radiotherapy to the lung within 6 months of randomization
* Uncontrolled tumor-related pain
* Unresolved toxicities from prior anticancer therapy
* History of malignancy within 5 years prior to screening, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \>90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
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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Banner Health MD Anderson AZ

Gilbert, Arizona, United States

Site Status

Los Angeles Cancer Network

Los Angeles, California, United States

Site Status

UCLA Hematology / Oncology Clinic

Los Angeles, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

Yale Cancer Center

New Haven, Connecticut, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Florida Cancer Specialists - North;725 6th Ave South (St. Petersburg)

St. Petersburg, Florida, United States

Site Status

University of Chicago Medical Center

Chicago, Illinois, United States

Site Status

New England Cancer Specialists

Westbrook, Maine, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Cancer and Hematology Centers of Western Michigan

Grand Rapids, Michigan, United States

Site Status

Minnesota Oncology Edina

Edina, Minnesota, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Taylor Cancer Research Center

Maumee, Ohio, United States

Site Status

Oncology Associates of Oregon, P.C

Eugene, Oregon, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Allegheny Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Tennessee Oncology, PLLC - Chattanooga

Chattanooga, Tennessee, United States

Site Status

Baptist Clinical Research Institute

Memphis, Tennessee, United States

Site Status

Tennessee Oncology

Nashville, Tennessee, United States

Site Status

JPS Health Network

Fort Worth, Texas, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Texas Oncology - Northeast Texas

Longview, Texas, United States

Site Status

Hospital Britanico

Buenos Aires, , Argentina

Site Status

Centro Oncologico Korben

Ciudad Autonoma Buenos Aires, , Argentina

Site Status

Liverpool Hospital

Liverpool, New South Wales, Australia

Site Status

GenesisCare North Shore

St Leonards, New South Wales, Australia

Site Status

Sunshine Coast University Hospital

Birtinya, Queensland, Australia

Site Status

Lyell McEwin Hospital

Elizabeth Vale, South Australia, Australia

Site Status

Peter Maccallum Cancer Centre

Melbourne, Victoria, Australia

Site Status

Krankenhaus Nord - Klinik Floridsdorf

Vienna, , Austria

Site Status

AZORG Campus Aalst-Moorselbaan

Aalst, , Belgium

Site Status

UZ Brussel

Brussels, , Belgium

Site Status

Cliniques Universitaires St-Luc

Brussels, , Belgium

Site Status

UZ Antwerpen

Edegem, , Belgium

Site Status

Jessa Zkh (Campus Virga Jesse)

Hasselt, , Belgium

Site Status

CHU de Liège (Sart Tilman)

Liège, , Belgium

Site Status

CHU UCL Mont-Godinne

Mont-godinne, , Belgium

Site Status

AZ Delta (Campus Rumbeke)

Roeselare, , Belgium

Site Status

Vitaz

Sint-Niklaas, , Belgium

Site Status

ZAS Sint Augustinus Wilrijk

Wilrijk, , Belgium

Site Status

Hospital Sao Rafael - HSR

Salvador, Estado de Bahia, Brazil

Site Status

Hospital de Cancer de Barretos

Barretos, São Paulo, Brazil

Site Status

Hospital de Base de Sao Jose do Rio Preto

São José do Rio Preto, São Paulo, Brazil

Site Status

Hospital Sírio-Libanês

São Paulo, São Paulo, Brazil

Site Status

Hospital Alemao Oswaldo Cruz

São Paulo, São Paulo, Brazil

Site Status

William Osler Health Centre - Brampton Civic Hospital

Brampton, Ontario, Canada

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

Aarhus Universitetshospital

Aarhus N, , Denmark

Site Status

Herlev Hospital

Herlev, , Denmark

Site Status

Regionshospitalet Gødstrup

Herning, , Denmark

Site Status

Helsinki University Central Hospital

Helsinki, , Finland

Site Status

Kuopio Uni Hospital

Kuopio, , Finland

Site Status

CHRU Brest

Brest, , France

Site Status

Chu Toulouse

Bron, , France

Site Status

Hopital Louis Pradel

Bron, , France

Site Status

CHRU Lille

Lille, , France

Site Status

Centre Leon Berard

Lyon, , France

Site Status

CHU Montpellier

Montpellier, , France

Site Status

Centre Antoine Lacassagne Centre Régional de Lutte Contre Le Cancer

Nice, , France

Site Status

Hopital Tenon

Paris, , France

Site Status

CHU Bordeaux

Pessac, , France

Site Status

CH de Saint Quentin

Saint-Quentin, , France

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Chru de Strasbourg

Strasbourg, , France

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Hia Sainte Anne

Toulon, , France

Site Status

Evangelische Lungenklinik Berlin

Berlin, , Germany

Site Status

Helios Klinikum Emil von Behring GmbH

Berlin, , Germany

Site Status

Klinikum Koeln-Merheim

Cologne, , Germany

Site Status

KEM/Evang. Kliniken Essen Mitte gGmbH

Essen, , Germany

Site Status

Universitätsklinikum Essen

Essen, , Germany

Site Status

Klinikum Esslingen

Esslingen am Neckar, , Germany

Site Status

Asklepios Fachkliniken GmbH

Gauting, , Germany

Site Status

LungenClinic Großhansdorf GmbH

Großhansdorf, , Germany

Site Status

Thoraxklinik Heidelberg gGmbH

Heidelberg, , Germany

Site Status

Lungenklinik Hemer

Hemer, , Germany

Site Status

Universität Des Saarlandes

Homburg, , Germany

Site Status

SLK Kliniken Heilbronn GmbH, Standort Fachklinik Löwenstein

Löwenstein, , Germany

Site Status

Universitätsklinikum Schleswig-Holstein

Lübeck, , Germany

Site Status

Klinikum Bogenhausen

München, , Germany

Site Status

Universitätsklinikum Münster, Medizinische Klinik A, Translationale Onkologie

Münster, , Germany

Site Status

Universitätsklinikum Regensburg

Regensburg, , Germany

Site Status

Klinikum Würzburg Mitte gGmbH

Würzburg, , Germany

Site Status

Uoa Sotiria Hospital

Athens, , Greece

Site Status

Errikos Dynan Hospital

Athens, , Greece

Site Status

University Hospital of Larissa

Larissa, , Greece

Site Status

Theageneio Hospital

Thessaloniki, , Greece

Site Status

Ag. Loukas Hospital

Thessaloniki, , Greece

Site Status

Tuen Mun Hospital

Hong Kong, , Hong Kong

Site Status

Prince of Wales Hosp

Shatin, , Hong Kong

Site Status

Irccs Ist. Tumori Giovanni Paolo Ii

Bari, Apulia, Italy

Site Status

A.O. Universitaria Di Parma

Parma, Emilia-Romagna, Italy

Site Status

IRCCS Istituto Regina Elena (IFO)

Rome, Lazio, Italy

Site Status

Ospedale Policlinico San Martino

Genoa, Liguria, Italy

Site Status

Ospedale Civile SS Annunziata

Sassari, Sardinia, Italy

Site Status

Azienda Ospedaliero-Universitaria Careggi

Florence, Tuscany, Italy

Site Status

Azienda Ospedaliero Universitaria Pisana

Pisa, Tuscany, Italy

Site Status

IRCCS Istituto Oncologico Veneto (IOV)

Padua, Veneto, Italy

Site Status

Kyushu University Hospital

Fukuoka, , Japan

Site Status

Sendai Kousei Hospital

Miyagi, , Japan

Site Status

Kindai University Hospital

Osaka, , Japan

Site Status

National Cancer Center Hospital

Tokyo, , Japan

Site Status

The Cancer Institute Hospital of JFCR

Tokyo, , Japan

Site Status

Wakayama Medical University Hospital

Wakayama, , Japan

Site Status

ARKE Estudios Clínicos S.A. de C.V.

Mexico City, , Mexico

Site Status

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, , Netherlands

Site Status

Ziekenhuis Rijnstate

Arnhem, , Netherlands

Site Status

Amphia Ziekenhuis

Breda, , Netherlands

Site Status

Ziekenhuis St. Jansdal

Harderwijk, , Netherlands

Site Status

Medisch Centrum Haaglanden, locatie Antoniushove

Leidschendam, , Netherlands

Site Status

Isala

Zwolle, , Netherlands

Site Status

Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii

Gdansk, , Poland

Site Status

Instytut Gruzlicy I Chorob Pluc

Warsaw, , Poland

Site Status

Dolno?L?Skie Centrum Onkologii, Pulmonologii I Hematologii

Wroc?aw, , Poland

Site Status

Hospital de Braga

Braga, , Portugal

Site Status

CHUC - Unidade de Pneumologia Oncológica

Coimbra, , Portugal

Site Status

Centro Clinico Champalimaud

Lisbon, , Portugal

Site Status

Centro Hospitalar do Porto ? Hospital de Santo António

Porto, , Portugal

Site Status

IPO do Porto

Porto, , Portugal

Site Status

National Cancer Centre

Singapore, , Singapore

Site Status

St. Vincent's Hospital

Gyeonggi-do, , South Korea

Site Status

Gachon University Gil Medical Center

Incheon, , South Korea

Site Status

Chonnam National University Hwasun Hospital

Jeollanam-do, , South Korea

Site Status

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Institut Catala d Oncologia Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

Site Status

Hospital Nuestra Senora de Valme

Seville, Sevilla, Spain

Site Status

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Site Status

Hospital Vall Hebron

Barcelona, , Spain

Site Status

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Site Status

Hospital Regional Universitario de Malaga

Málaga, , Spain

Site Status

Hospital Universitario la Fe

Valencia, , Spain

Site Status

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Site Status

Gävle Sjukhus

Gävle, , Sweden

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Chang Gung Medical Foundation - Linkou

Taoyuan District, , Taiwan

Site Status

Vajira Hospital

Bangkok, , Thailand

Site Status

Siriraj Hospital - Chulabhorn Bone Marrow Transplant Centre

Bangkok, , Thailand

Site Status

Songklanagarind Hospital

Songkhla, , Thailand

Site Status

Addenbrooke's Hospital

Cambridge, , United Kingdom

Site Status

Castle Hill Hospital

Cottingham, , United Kingdom

Site Status

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status

St James University Hospital

Leeds, , United Kingdom

Site Status

Guy's Hospital - Cancer Centre

London, , United Kingdom

Site Status

Royal Marsden Hospital - London

London, , United Kingdom

Site Status

Nottingham City Hospital

Nottingham, , United Kingdom

Site Status

Royal Marsden Hospital (Sutton)

Sutton, , United Kingdom

Site Status

Torbay Hospital

Torquay, , United Kingdom

Site Status

Countries

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United States Argentina Australia Austria Belgium Brazil Canada Denmark Finland France Germany Greece Hong Kong Italy Japan Mexico Netherlands Poland Portugal Singapore South Korea Spain Sweden Taiwan Thailand United Kingdom

Other Identifiers

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2024-510908-37-00

Identifier Type: OTHER

Identifier Source: secondary_id

BO45217

Identifier Type: -

Identifier Source: org_study_id

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