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

NCT06497556 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: BO452172024-510908-37-00
• Study Type: interventional
• Target: 338
• Locations: 25 countries
• Sites: 150

Brief Summary

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).

Conditions

Non-Small Cell Lung Cancer; KRAS G12C Lung Cancer

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

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by blinded independent central review (BICR) according to RECIST v1.1, or death from any cause (whichever occurs first)

  Up to approximately 4 years

Secondary Outcomes (12)

• Overall Survival (OS)

  Up to approximately 4 years

• Confirmed Objective Response

  Up to approximately 4 years

• Time to Confirmed Deterioration (TTCD) on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Dyspnea Item and Physical Functioning Scale

  Baseline up to approximately 4 years

• TTCD on the EORTC Quality-of-Life Questionnaire-Supplemental Lung Cancer Module (QLQ-LC13) Cough Scale

  Baseline up to approximately 4 years

• Duration of Response (DOR)

  Up to approximately 4 years

Study Arms (2)

Divarasib

EXPERIMENTAL

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

Drug: Divarasib

KRAS G12C inhibitor

ACTIVE COMPARATOR

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

Drug: Sotorasib; Drug: Adagrasib

Interventions

Divarasib DRUG

Divarasib will be administered orally QD

Divarasib

Sotorasib DRUG

Sotorasib will be administered orally QD

KRAS G12C inhibitor

Adagrasib DRUG

Adagrasib will be administred orally BID

KRAS G12C inhibitor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Chugai Pharmaceutical: collaborator

Study Sites (151)

Banner Health MD Anderson AZ

Gilbert, Arizona, 85234, United States

Location

Los Angeles Cancer Network

Los Angeles, California, 90017-4803, United States

Location

UCLA Hematology / Oncology Clinic

Los Angeles, California, 90095, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06519, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

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

St. Petersburg, Florida, 33701-4553, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

New England Cancer Specialists

Westbrook, Maine, 04092, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109-0934, United States

Location

Cancer and Hematology Centers of Western Michigan

Grand Rapids, Michigan, 49503, United States

Location

Minnesota Oncology Edina

Edina, Minnesota, 55435, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Taylor Cancer Research Center

Maumee, Ohio, 43537, United States

Location

Oncology Associates of Oregon, P.C

Eugene, Oregon, 97401, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Allegheny Cancer Center

Pittsburgh, Pennsylvania, 15212, United States

Location

Tennessee Oncology, PLLC - Chattanooga

Chattanooga, Tennessee, 37404, United States

Location

Baptist Clinical Research Institute

Memphis, Tennessee, 38120, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

JPS Health Network

Fort Worth, Texas, 76104, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Oncology - Northeast Texas

Longview, Texas, 75601, United States

Location

Hospital Britanico

Buenos Aires, C1280AEB, Argentina

Location

Centro Oncologico Korben

Ciudad Autonoma Buenos Aires, C1426AGE, Argentina

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

GenesisCare North Shore

St Leonards, New South Wales, 2065, Australia

Location

Sunshine Coast University Hospital

Birtinya, Queensland, 4575, Australia

Location

Lyell McEwin Hospital

Elizabeth Vale, South Australia, 5112, Australia

Location

Peter Maccallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Krankenhaus Nord - Klinik Floridsdorf

Vienna, 1210, Austria

Location

AZORG Campus Aalst-Moorselbaan

Aalst, 9300, Belgium

Location

UZ Brussel

Brussels, 1090, Belgium

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

Jessa Zkh (Campus Virga Jesse)

Hasselt, 3500, Belgium

Location

CHU de Liège (Sart Tilman)

Liège, 4000, Belgium

Location

CHU UCL Mont-Godinne

Mont-godinne, 5530, Belgium

Location

AZ Delta (Campus Rumbeke)

Roeselare, 8800, Belgium

Location

Vitaz

Sint-Niklaas, 9100, Belgium

Location

ZAS Sint Augustinus Wilrijk

Wilrijk, 2610, Belgium

Location

Hospital Sao Rafael - HSR

Salvador, Estado de Bahia, 41253-190, Brazil

Location

Hospital de Cancer de Barretos

Barretos, São Paulo, 14784-400, Brazil

Location

Hospital de Base de Sao Jose do Rio Preto

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

Hospital Sírio-Libanês

São Paulo, São Paulo, 01308-050, Brazil

Location

Hospital Alemao Oswaldo Cruz

São Paulo, São Paulo, 01323-903, Brazil

Location

William Osler Health Centre - Brampton Civic Hospital

Brampton, Ontario, L6R 3J7, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Aarhus Universitetshospital

Aarhus N, 8200, Denmark

Location

Herlev Hospital

Herlev, 2730, Denmark

Location

Regionshospitalet Gødstrup

Herning, 7400, Denmark

Location

Helsinki University Central Hospital

Helsinki, 00029, Finland

Location

Kuopio Uni Hospital

Kuopio, 70211, Finland

Location

CHRU Brest

Brest, 29200, France

Location

Chu Toulouse

Bron, 69500, France

Location

Hopital Louis Pradel

Bron, 69677, France

Location

CHRU Lille

Lille, 59037, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

CHU Montpellier

Montpellier, 34295, France

Location

Centre Antoine Lacassagne Centre Régional de Lutte Contre Le Cancer

Nice, 06100, France

Location

Hopital Tenon

Paris, 75970, France

Location

CHU Bordeaux

Pessac, 33604, France

Location

CH de Saint Quentin

Saint-Quentin, 2100, France

Location

Chru de Strasbourg

Strasbourg, 67091, France

Location

Hia Sainte Anne

Toulon, 83041, France

Location

Evangelische Lungenklinik Berlin

Berlin, 13125, Germany

Location

Helios Klinikum Emil von Behring GmbH

Berlin, 14165, Germany

Location

Klinikum Koeln-Merheim

Cologne, 51109, Germany

Location

KEM/Evang. Kliniken Essen Mitte gGmbH

Essen, 45136, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Klinikum Esslingen

Esslingen am Neckar, 73730, Germany

Location

Asklepios Fachkliniken GmbH

Gauting, 82131, Germany

Location

LungenClinic Großhansdorf GmbH

Großhansdorf, 22927, Germany

Location

Thoraxklinik Heidelberg gGmbH

Heidelberg, 69126, Germany

Location

Lungenklinik Hemer

Hemer, 58675, Germany

Location

Universität Des Saarlandes

Homburg, 66421, Germany

Location

SLK Kliniken Heilbronn GmbH, Standort Fachklinik Löwenstein

Löwenstein, 74245, Germany

Location

Universitätsklinikum Schleswig-Holstein

Lübeck, 23538, Germany

Location

Klinikum Bogenhausen

München, 81925, Germany

Location

Universitätsklinikum Münster, Medizinische Klinik A, Translationale Onkologie

Münster, 48149, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

Location

Klinikum Würzburg Mitte gGmbH

Würzburg, 97074, Germany

Location

Uoa Sotiria Hospital

Athens, 115 27, Greece

Location

Errikos Dynan Hospital

Athens, 11526, Greece

Location

University Hospital of Larissa

Larissa, 411 10, Greece

Location

Theageneio Hospital

Thessaloniki, 546 39, Greece

Location

Ag. Loukas Hospital

Thessaloniki, 55236, Greece

Location

Tuen Mun Hospital

Hong Kong, Hong Kong

Location

Prince of Wales Hosp

Shatin, Hong Kong

Location

Irccs Ist. Tumori Giovanni Paolo Ii

Bari, Apulia, 70124, Italy

Location

A.O. Universitaria Di Parma

Parma, Emilia-Romagna, 43100, Italy

Location

IRCCS Istituto Regina Elena (IFO)

Rome, Lazio, 00144, Italy

Location

Ospedale Policlinico San Martino

Genoa, Liguria, 16132, Italy

Location

Ospedale Civile SS Annunziata

Sassari, Sardinia, 07100, Italy

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, Tuscany, 50139, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, Tuscany, 56126, Italy

Location

IRCCS Istituto Oncologico Veneto (IOV)

Padova, Veneto, 35128, Italy

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Sendai Kousei Hospital

Miyagi, 981-0914, Japan

Location

Kindai University Hospital

Osaka, 589-8511, Japan

Location

National Cancer Center Hospital

Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital of JFCR

Tokyo, 135-8550, Japan

Location

Wakayama Medical University Hospital

Wakayama, 641-8510, Japan

Location

ARKE Estudios Clínicos S.A. de C.V.

Mexico City, 06700, Mexico

Location

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, 5223 GZ, Netherlands

Location

Ziekenhuis Rijnstate

Arnhem, 6815 AD, Netherlands

Location

Amphia Ziekenhuis

Breda, 4818CK, Netherlands

Location

Ziekenhuis St. Jansdal

Harderwijk, 3844 DG, Netherlands

Location

Medisch Centrum Haaglanden, locatie Antoniushove

Leidschendam, 2262 BA, Netherlands

Location

Isala

Zwolle, 8025 AB, Netherlands

Location

Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii

Gdansk, 80-214, Poland

Location

Instytut Gruzlicy I Chorob Pluc

Warsaw, 01-138, Poland

Location

Dolno?L?Skie Centrum Onkologii, Pulmonologii I Hematologii

Wroc?aw, 53-439, Poland

Location

Hospital de Braga

Braga, 4710-243, Portugal

Location

CHUC - Unidade de Pneumologia Oncológica

Coimbra, 3000-075, Portugal

Location

Centro Clinico Champalimaud

Lisbon, 1400-038, Portugal

Location

Centro Hospitalar do Porto ? Hospital de Santo António

Porto, 4099-001, Portugal

Location

IPO do Porto

Porto, 4200-072, Portugal

Location

National Cancer Centre

Singapore, 168583, Singapore

Location

St. Vincent's Hospital

Gyeonggi-do, 16247, South Korea

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Chonnam National University Hwasun Hospital

Jeollanam-do, 58128, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, 463-707, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Institut Catala d Oncologia Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Nuestra Senora de Valme

Seville, Sevilla, 41014, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Vall Hebron

Barcelona, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, 29010, Spain

Location

Hospital Universitario la Fe

Valencia, 46026, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Gävle Sjukhus

Gävle, 80187, Sweden

Location

National Taiwan University Hospital

Taipei, 00100, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Chang Gung Medical Foundation - Linkou

Taoyuan District, 333, Taiwan

Location

Vajira Hospital

Bangkok, 10300, Thailand

Location

Siriraj Hospital - Chulabhorn Bone Marrow Transplant Centre

Bangkok, 10700, Thailand

Location

Songklanagarind Hospital

Songkhla, 90110, Thailand

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Castle Hill Hospital

Cottingham, HU16 5JQ, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

St James University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Guy's Hospital - Cancer Centre

London, SE1 9RT, United Kingdom

Location

Royal Marsden Hospital - London

London, SW3 6JJ, United Kingdom

Location

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

Royal Marsden Hospital (Sutton)

Sutton, SM2 5PT, United Kingdom

Location

Torbay Hospital

Torquay, TQ27AA, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

sotorasib; adagrasib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2024
• First Posted: July 11, 2024
• Study Start: September 23, 2024
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): November 30, 2029
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

AR (2); DK (3); GR (5); NL (6); TH (3); AU (5); BE (10); SE (1); US (25); DE (17); ES (8); PL (3); KR (6); CA (2); GB (9); SG (1); PT (5); FR (12); ME (1); TW (3); HK (2); IT (8); JP (6); BR (5); FI (2)