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

NCT05789082 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: BO444262022-003048-282023-507171-22-00
• Study Type: interventional
• Target: 320
• Locations: 18 countries
• Sites: 71

Brief 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).

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants with Adverse Events (AEs)

  Baseline until 60 days after the final dose of study treatment or until initiation of another anti-cancer therapy, whichever occurs first (up to approximately 5 years)

Secondary Outcomes (11)

• Objective Response Rate (ORR)

  Approximately 5 years

• Duration of Response (DOR)

  Approximately 5 years

• Progression Free Survival (PFS)

  Approximately 5 years

• Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Side Effects as Assessed Through the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE)

  Approximately 5 years

• Change from Baseline in Symptomatic Side Effects, as Assessed Through use of the PRO-CTCAE

  Baseline up to approximately 5 years

Study Arms (4)

Cohort A - Combination Dose Finding + Dose Expansion

EXPERIMENTAL

Participants will be enrolled in different cohorts to receive divarasib (different dose levels will be evaluated) once a day (QD) combined with pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W). During the expansion stage, some participants are planned to be randomized to one divarasib combination dose level; other participants are planned to be randomized to another divarasib combination dose level. Divarasib will be given in combination with pembrolizumab.

Drug: Divarasib; Drug: Pembrolizumab

Cohort B - Combination Dose Finding + Dose Expansion

EXPERIMENTAL

Participants enrolled in this cohort will receive divarasib (different dose levels will be evaluated) QD combined with pembrolizumab 200 mg IV Q3W plus investigator's choice of platinum-based chemotherapy (carboplatin or cisplatin) and pemetrexed.

Drug: Divarasib; Drug: Pembrolizumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed

Cohort C - Dose Expansion

EXPERIMENTAL

Participants enrolled in this cohort will receive one dose level of divarasib QD.

Drug: Divarasib

Cohort D - Dose Expansion

EXPERIMENTAL

Participants enrolled in this cohort will receive one dose level of divarasib QD.

Drug: Divarasib

Interventions

Divarasib DRUG

Participants will receive divarasib orally (PO), QD on days 1-21 of each 21-day cycle.

Cohort A - Combination Dose Finding + Dose Expansion; Cohort B - Combination Dose Finding + Dose Expansion; Cohort C - Dose Expansion; Cohort D - Dose Expansion

Pembrolizumab DRUG

Participants will receive a 200 mg IV infusion of pembrolizumab Q3W on Day 1 of each 21-day cycle.

Cohort A - Combination Dose Finding + Dose Expansion; Cohort B - Combination Dose Finding + Dose Expansion

Pemetrexed DRUG

Participants will receive IV pemetrexed Q3W.

Cohort B - Combination Dose Finding + Dose Expansion

Carboplatin DRUG

Participants will receive IV carboplatin Q3W for four 21-day cycles.

Cohort B - Combination Dose Finding + Dose Expansion

Cisplatin DRUG

Participants will receive IV cisplatin Q3W for four 21-day cycles.

Cohort B - Combination Dose Finding + Dose Expansion

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (71)

City of Hope National Medical Center

Duarte, California, 91010, United States

WITHDRAWN

City of Hope - Seacliff

Huntington Beach, California, 92648, United States

WITHDRAWN

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

WITHDRAWN

UCSD Moores Cancer Center

La Jolla, California, 92093, United States

WITHDRAWN

City of Hope - Long Beach Elm

Long Beach, California, 90813, United States

WITHDRAWN

Yale Cancer Center

New Haven, Connecticut, 06520, United States

RECRUITING

Florida Cancer Specialists - SOUTH - SCRI - PPDS

Fort Myers, Florida, 33901-8108, United States

RECRUITING

Florida Cancer Specialists - NORTH - SCRI - PPDS

St. Petersburg, Florida, 33705-1400, United States

RECRUITING

Florida Cancer Specialists - EAST - SCRI - PPDS

West Palm Beach, Florida, 33401-3406, United States

RECRUITING

NYU Langone Hospital - Long Island

Mineola, New York, 11501, United States

RECRUITING

NYU Cancer Center

New York, New York, 10016, United States

RECRUITING

Mount SInai Medical Center

New York, New York, 10029, United States

RECRUITING

Montefiore Medical Center - Montefiore Medical Park

The Bronx, New York, 10461, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Oncology & Hematology Associates of Southwest Virginia, Inc

Blacksburg, Virginia, 24060, United States

RECRUITING

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

RECRUITING

Hospital Britanico

Buenos Aires, C1280AEB, Argentina

RECRUITING

Clinica Adventista Belgrano

Ciudad Autonoma Buenos Aires, C1430EGF, Argentina

RECRUITING

Centro Oncologico Riojano Integral (CORI)

La Rioja, F5300COE, Argentina

RECRUITING

Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia

COMPLETED

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

Alfred Health

Melbourne, Victoria, 3004, Australia

RECRUITING

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

RECRUITING

Jessa Zkh (Campus Virga Jesse)

Hasselt, 3500, Belgium

RECRUITING

Clinique Ste-Elisabeth

Namur, 5000, Belgium

RECRUITING

AZ Delta (Campus Rumbeke)

Roeselare, 8800, Belgium

RECRUITING

Hospital de Cancer de Barretos

Barretos, São Paulo, 14784-400, Brazil

RECRUITING

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, 01246-000, Brazil

RECRUITING

Ottawa Hospital Regional Cancer Centre

Ottawa, Ontario, K1H 8M2, Canada

RECRUITING

Princess Margaret Cancer Center

Toronto, Ontario, M5G 1Z5, Canada

ACTIVE NOT RECRUITING

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

Hunan Cancer Hospital

Changsha, 410013, China

ACTIVE NOT RECRUITING

Harbin Medical University Cancer Hospital

Harbin, 150081, China

RECRUITING

Shanghai Pulmonary Hospital

Shanghai, 200433, China

ACTIVE NOT RECRUITING

Rambam Medical Center

Haifa, 3109601, Israel

RECRUITING

Rabin MC

Petah Tikva, 4941492, Israel

RECRUITING

Tel Aviv Sourasky Medical Ctr

Tel Aviv, 6423906, Israel

RECRUITING

Istituto Nazionale Tumori Fondazione G. Pascale

Naples, Campania, 80131, Italy

WITHDRAWN

Policlinico Universitario Agostino Gemelli IRCCS

Rome, Lazio, 00168, Italy

ACTIVE NOT RECRUITING

Irccs Istituto Nazionale Dei Tumori (Int)

Milan, Lombardy, 20133, Italy

RECRUITING

A.O. Universitaria S. Luigi Gonzaga

Orbassano, Piedmont, 10043, Italy

RECRUITING

National Cancer Center Hospital East

Chiba, 277-8577, Japan

RECRUITING

Kindai University Hospital

Osaka, 589-8511, Japan

RECRUITING

National Cancer Center Hospital

Tokyo, 104-0045, Japan

RECRUITING

The Cancer Institute Hospital of JFCR

Tokyo, 135-8550, Japan

RECRUITING

Wakayama Medical University Hospital

Wakayama, 641-8510, Japan

RECRUITING

NKI The Netherlands Cancer Institute

Amsterdam, 1066 CX, Netherlands

ACTIVE NOT RECRUITING

UMC St Radboud

Nijmegen, 6525 GA, Netherlands

RECRUITING

Uniwersyteckie Centrum Kliniczne

Gda?sk, 80-214, Poland

RECRUITING

Krakowski Szpital Specjalistyczny im sw. Jana Paw?a II

Krakow, 31-202, Poland

RECRUITING

Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie

Olsztyn, 10-357, Poland

ACTIVE NOT RECRUITING

Pusan National University Hospital

Busan, 49241, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Korea University Guro Hospital

Seoul, 08308, South Korea

RECRUITING

ICO Badalona-H.U. Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

RECRUITING

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

Barcelona, 08035, Spain

RECRUITING

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

Sahlgrenska University Hospital

Gothenburg, 411 36, Sweden

RECRUITING

Universitätsspital Basel

Basel, 4031, Switzerland

RECRUITING

Inselspital Bern

Bern, 3010, Switzerland

WITHDRAWN

Taichung Veterans General Hospital

Taichung, 407, Taiwan

RECRUITING

National Cheng Kung University Hospital

Tainan, Taiwan

RECRUITING

National Taiwan Uni Hospital

Taipei, 100, Taiwan

RECRUITING

Chang Gung Medical Foundation - Linkou

Taoyuan District, 333, Taiwan

ACTIVE NOT RECRUITING

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

RECRUITING

Barts & London School of Med

London, EC1A 7BE, United Kingdom

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Carboplatin; Cisplatin; Pemetrexed

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: BO44426 https://forpatients.roche.com/

CONTACT

888-662-6728 (U.S. and Canada); global-roche-genentech-trials@gene.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Cohorts B, C, D, and a subset of Cohort A follow non-randomized allocation; other subsets of Cohort A are randomized.

Study Record Dates

• First Submitted: February 21, 2023
• First Posted: March 29, 2023
• Study Start: June 20, 2023
• Primary Completion (Estimated): January 29, 2032
• Study Completion (Estimated): January 29, 2032
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

AR (3); JP (5); BR (2); PL (3); US (16); TW (4); CN (3); CA (3); ES (6); GB (2); IT (4); KR (5); IL (3); SE (1); BE (4); CH (2); NL (2); AU (3)