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NCT07541170PHASE3Recruiting

A Study to Evaluate the Efficacy and Safety of Divarasib Compared With Investigator's Choice of Immunotherapy or Observation in Participants With Resected Stage II-III KRAS G12C-Positive Non-Small Cell Lung Cancer (NSCLC)

Hoffmann-La Roche

Start Date

10/6/2026

Completion Date

3/31/2035

Summary

The main purpose of this study is to evaluate the efficacy of divarasib compared with investigator's choice of immunotherapy (pembrolizumab or nivolumab) or observation in participants with resected Kirsten rat sarcoma viral oncogene homolog glycine 12 to cysteine (KRAS G12C)-positive Stage II-IIIB NSCLC, regardless of tumor programmed death-ligand 1 (PD-L1) status, who have not achieved pathologic complete response (pCR) following neoadjuvant chemoimmunotherapy.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Histological or cytological diagnosis of clinical Stage II-IIIB NSCLC of either non-squamous or squamous histology * Participants must have had complete resection of NSCLC * Prior treatment with neoadjuvant immune checkpoint inhibitor (pembrolizumab or nivolumab) in combination with histology-based platinum-based doublet chemotherapy * Participants must be randomized within 12 weeks of their surgery date * No evidence of disease recurrence or metastatic disease * Documentation of the presence of a KRAS G12C mutation Exclusion Criteria: * Participants who achieve pCR following neoadjuvant treatment * Prior treatment with a KRAS inhibitor or any other anti-cancer therapy not otherwise specified in the protocol * Prior treatment with radiation therapy for NSCLC, with the exception of localized symptom-directed radiation prior to surgical resection * Resolved Grade 3 or greater immune-related AE or unresolved Grade 2 or greater immune-related AE from neoadjuvant immunotherapy * Active or history of autoimmune disease or immune deficiency * Significant cardiovascular disease

Interventions

DRUG

Divarasib

DRUG

Pembrolizumab

DRUG

Nivolumab

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Conditions

Non-small Cell Lung Cancer

Locations

Community Cancer Institute (CCI)

Clovis, California 93611

United States

Piedmont Cancer Institute, PC

Atlanta, Georgia 30318

United States

Profound Research, LLC

Farmington Hills, Michigan 48334

United States

Renown Regional Medical Center

Reno, Nevada 89502

United States

Cancer Care Specialists

Reno, Nevada 89511

United States

San Juan Oncology Associates

Farmington, New Mexico 87401

United States

Sanatorio de la Mujer

Rosario, Santa Fe Province S2000ORE

Argentina

Instituto Argentino de Diagnóstico y Tratamiento- IADT

Capital Federal, C1122AAL

Argentina

Hospital Britanico

Ciudad Autonoma Buenos Aires, C1280AEB

Argentina

Centro Oncologico Korben

Ciudad Autonoma Buenos Aires, C1426AGE

Argentina

Clinica Adventista Belgrano

Ciudad Autonoma Buenos Aires, C1430EGF

Argentina

Hospital Privado De Comunidad

Mar del Plata, B7602CBM

Argentina

Cenantron - Centro Avancado de Tratamento Oncologico

Belo Horizonte, Minas Gerais 30130-090

Brazil

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul 90035-001

Brazil

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul 90610-000

Brazil

Clinica de Neoplasias Litoral

Itajaí, Santa Catarina 88301-220

Brazil

Beneficencia Portuguesa de Sao Paulo

São Paulo, 01321-00

Brazil

Jewish General Hospital

Montreal, Quebec H3T 1E2

Canada

Guangdong General Hospital

Guangzhou, 510030

China

Fundación CTIC - Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo

Bogota, D.C., 110131

Colombia

Clinica ASTORGA

Medellín, 50010

Colombia

Attikon University General Hospital

Athens, 124 61

Greece

Athens Medical Center

Marousi, 151 25

Greece

Queen Mary Hospital

Hong Kong,

Hong Kong

Prince of Wales Hosp

Shatin,

Hong Kong

Ospedale P. Pederzoli Casa di cura Privata

Peschiera Del Garda (VR), Veneto 37019

Italy

Gifu University Hospital

Gifu, 501-1194

Japan

Kobe University Hospital

Hyōgo, 650-0017

Japan

Centrum Pulmonologii i Torakochirurgii

Bystra, 43-360

Poland

Uniwersyteckie Centrum Kliniczne, O?rodek Bada? Klinicznych Wczesnych Faz

Gda?sk, 80-214

Poland

?wi?tokrzyskie Centrum Onkologii Samodzielny Publiczny Zak?ad Opieki Zdrowotnej w Kielcach;Klinika Onkologii Klinicznej

Kielce, 25-734

Poland

Centro Clinico Champalimaud

Lisbon, 1400-038

Portugal

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggido 13620

South Korea

Pusan National University Hospital

Busan, 602-739

South Korea

Yeungnam University Medical Center

Daegu, 42415

South Korea

Chungnam National University Hospital

Daejeon, 35015

South Korea

Ajou University Medical Center

Gyeonggi-do, 16499

South Korea

Gachon University Gil Medical Center

Incheon, 21565

South Korea

Chonnam National University Hwasun Hospital

Jeollanam-do, 58128

South Korea

Severance Hospital, Yonsei University Health System

Seoul, 03722

South Korea

Asan Medical Center

Seoul, 05505

South Korea

Hospital de Basurto

Bilbao, Vizcaya 48013

Spain

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, 15006

Spain

Hospital General Univ. de Alicante

Alicante, 03010

Spain

Hospital Universitario San Cecilio

Granada, 18016

Spain

Hospital Universitario Miguel Servet

Zaragoza, 50009

Spain