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NCT05789082PHASE1, PHASE2Recruiting

A Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib as a Single Agent or in Combination With Other Anti-Cancer Therapies in Participants With Previously Untreated Advanced or Metastatic Non-Small Cell Lung Cancer With a KRAS G12C Mutation

Hoffmann-La Roche

Start Date

6/20/2023

Completion Date

1/29/2032

Summary

The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and activity of single-agent divarasib or combined with other anti-cancer therapies in participants with previously untreated, advanced or metastatic non-small cell lung cancer (NSCLC).

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Confirmation of Biomarker eligibility * Pre-treatment tumor tissue along with an associated pathology report is required for all participants enrolled on study. Representative tumor specimens must be in formalin-fixed, paraffin embedded (FFPE) blocks (preferred) or 15 unstained, freshly cut, serial slides. Although 15 slides are required, if only 10 slides are available, the participant may be eligible for the study following consultation with the Sponsor. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 * Histologically or cytologically documented locally advanced unresectable or metastatic NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy * No prior systemic treatment for advanced unresectable or metastatic NSCLC * Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Additionally, for participants in cohort D, measurable brain metastases defined as at least 5 millimeters and twice the slice thickness, but less than 20 mm, that is asymptomatic and does not require local therapy at the time of enrollment. Exclusion Criteria: * Known concomitant second oncogenic driver with available targeted treatment * Squamous cell histology NSCLC * Symptomatic, untreated, or actively progressing CNS metastases (Cohorts A, B, and C) * Prior treatment with a KRAS G12C inhibitor * Known hypersensitivity to any of the components of divarasib or pembrolizumab; or known hypersensitivity to pemetrexed, carboplatin, or cisplatin (Cohort B only) * History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis, active tuberculosis, significant cardiovascular disease within 3 months prior to initiation of study treatment * History of malignancy other than NSCLC within 5 years prior to initiation of study treatment, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate more \>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 * Uncontrolled tumor related pain, pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, uncontrolled or symptomatic hypercalcemia * Co-morbid condition that is an absolute contraindication to treatment with corticosteroids * Inability or unwillingness to take prophylactic treatments such as corticosteroids, anti-emetics, folic acid, or vitamin B12 supplementation. * Participants with brain metastases for whom complete surgical resections is clinically appropriate

Interventions

DRUG

Divarasib

DRUG

Pembrolizumab

DRUG

Carboplatin

DRUG

Cisplatin

DRUG

Pemetrexed

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Conditions

Non-Small Cell Lung Cancer

Locations

City of Hope National Medical Center

Duarte, California 91010

United States

City of Hope - Seacliff

Huntington Beach, California 92648

United States

City of Hope at Irvine Lennar

Irvine, California 92618

United States

UCSD Moores Cancer Center

La Jolla, California 92093

United States

City of Hope - Long Beach Elm

Long Beach, California 90813

United States

Yale Cancer Center

New Haven, Connecticut 06520

United States

Florida Cancer Specialists - SOUTH - SCRI - PPDS

Fort Myers, Florida 33901-8108

United States

Florida Cancer Specialists - NORTH - SCRI - PPDS

St. Petersburg, Florida 33705-1400

United States

Florida Cancer Specialists - EAST - SCRI - PPDS

West Palm Beach, Florida 33401-3406

United States

NYU Langone Hospital - Long Island

Mineola, New York 11501

United States

NYU Cancer Center

New York, New York 10016

United States

Mount SInai Medical Center

New York, New York 10029

United States

Montefiore Medical Center - Montefiore Medical Park

The Bronx, New York 10461

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

Oncology & Hematology Associates of Southwest Virginia, Inc

Blacksburg, Virginia 24060

United States

Virginia Oncology Associates

Norfolk, Virginia 23502

United States

Hospital Britanico

Buenos Aires, C1280AEB

Argentina

Clinica Adventista Belgrano

Ciudad Autonoma Buenos Aires, C1430EGF

Argentina

Centro Oncologico Riojano Integral (CORI)

La Rioja, F5300COE

Argentina

Concord Repatriation General Hospital

Concord, New South Wales 2139

Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria 3000

Australia

Alfred Health

Melbourne, Victoria 3004

Australia

Cliniques Universitaires St-Luc

Brussels, 1200

Belgium

Jessa Zkh (Campus Virga Jesse)

Hasselt, 3500

Belgium

Clinique Ste-Elisabeth

Namur, 5000

Belgium

AZ Delta (Campus Rumbeke)

Roeselare, 8800

Belgium

Hospital de Cancer de Barretos

Barretos, São Paulo 14784-400

Brazil

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo 01246-000

Brazil

Ottawa Hospital Regional Cancer Centre

Ottawa, Ontario K1H 8M2

Canada

Princess Margaret Cancer Center

Toronto, Ontario M5G 1Z5

Canada

Jewish General Hospital

Montreal, Quebec H3T 1E2

Canada

Hunan Cancer Hospital

Changsha, 410013

China

Harbin Medical University Cancer Hospital

Harbin, 150081

China

Shanghai Pulmonary Hospital

Shanghai, 200433

China

Rambam Medical Center

Haifa, 3109601

Israel

Rabin MC

Petah Tikva, 4941492

Israel

Tel Aviv Sourasky Medical Ctr

Tel Aviv, 6423906

Israel

Istituto Nazionale Tumori Fondazione G. Pascale

Naples, Campania 80131

Italy

Policlinico Universitario Agostino Gemelli IRCCS

Rome, Lazio 00168

Italy

Irccs Istituto Nazionale Dei Tumori (Int)

Milan, Lombardy 20133

Italy

A.O. Universitaria S. Luigi Gonzaga

Orbassano, Piedmont 10043

Italy

National Cancer Center Hospital East

Chiba, 277-8577

Japan

Kindai University Hospital

Osaka, 589-8511

Japan

National Cancer Center Hospital

Tokyo, 104-0045

Japan

The Cancer Institute Hospital of JFCR

Tokyo, 135-8550

Japan

Wakayama Medical University Hospital

Wakayama, 641-8510

Japan

NKI The Netherlands Cancer Institute

Amsterdam, 1066 CX

Netherlands

UMC St Radboud

Nijmegen, 6525 GA

Netherlands

Uniwersyteckie Centrum Kliniczne

Gda?sk, 80-214

Poland

Krakowski Szpital Specjalistyczny im sw. Jana Paw?a II

Krakow, 31-202

Poland

Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie

Olsztyn, 10-357

Poland

Pusan National University Hospital

Busan, 49241

South Korea

Seoul National University Hospital

Seoul, 03080

South Korea

Asan Medical Center

Seoul, 05505

South Korea

Samsung Medical Center

Seoul, 06351

South Korea

Korea University Guro Hospital

Seoul, 08308

South Korea

ICO Badalona-H.U. Germans Trias i Pujol

Badalona, Barcelona 08916

Spain

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, 08035

Spain

Hospital General Universitario Gregorio Marañon

Madrid, 28007

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Hospital Universitario Virgen del Rocio

Seville, 41013

Spain

Hospital Clinico Universitario de Valencia

Valencia, 46010

Spain

Sahlgrenska University Hospital

Gothenburg, 411 36

Sweden

Universitätsspital Basel

Basel, 4031

Switzerland

Inselspital Bern

Bern, 3010

Switzerland

Taichung Veterans General Hospital

Taichung, 407

Taiwan

National Cheng Kung University Hospital

Tainan,

Taiwan

National Taiwan Uni Hospital

Taipei, 100

Taiwan

Chang Gung Medical Foundation - Linkou

Taoyuan, 333

Taiwan

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN

United Kingdom

Barts & London School of Med

London, EC1A 7BE

United Kingdom