A Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib 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
NCT ID: NCT05789082
Last Updated: 2025-11-10
Study Results
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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RECRUITING
PHASE1/PHASE2
240 participants
INTERVENTIONAL
2023-06-20
2032-01-29
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Cohort A - Combination Dose Finding + Dose Expansion
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.
Divarasib
Participants will receive one of two doses of divarasib orally (PO), QD on days 1-21 of each 21-day cycle.
Pembrolizumab
Participants will receive a 200 mg IV infusion of pembrolizumab Q3W on Day 1 of each 21-day cycle.
Cohort B - Combination Dose Finding + Dose Expansion
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.
Divarasib
Participants will receive one of two doses of divarasib orally (PO), QD on days 1-21 of each 21-day cycle.
Pembrolizumab
Participants will receive a 200 mg IV infusion of pembrolizumab Q3W on Day 1 of each 21-day cycle.
Carboplatin
Participants will receive IV carboplatin Q3W for four 21-day cycles.
Cisplatin
Participants will receive IV cisplatin Q3W for four 21-day cycles.
Pemetrexed
Participants will receive IV pemetrexed Q3W.
Interventions
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Divarasib
Participants will receive one of two doses of divarasib orally (PO), QD on days 1-21 of each 21-day cycle.
Pembrolizumab
Participants will receive a 200 mg IV infusion of pembrolizumab Q3W on Day 1 of each 21-day cycle.
Carboplatin
Participants will receive IV carboplatin Q3W for four 21-day cycles.
Cisplatin
Participants will receive IV cisplatin Q3W for four 21-day cycles.
Pemetrexed
Participants will receive IV pemetrexed Q3W.
Eligibility Criteria
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Inclusion Criteria
* 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
Exclusion Criteria
* Squamous cell histology NSCLC
* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
* 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.
18 Years
ALL
No
Sponsors
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Hoffmann-La Roche
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trials
Role: STUDY_DIRECTOR
Hoffmann-La Roche
Locations
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City of Hope National Medical Center
Duarte, California, United States
City of Hope - Seacliff
Huntington Beach, California, United States
City of Hope at Irvine Lennar
Irvine, California, United States
UCSD Moores Cancer Center
La Jolla, California, United States
City of Hope - Long Beach Elm
Long Beach, California, United States
Yale Cancer Center
New Haven, Connecticut, United States
Florida Cancer Specialists - SOUTH - SCRI - PPDS
Fort Myers, Florida, United States
Florida Cancer Specialists - NORTH - SCRI - PPDS
St. Petersburg, Florida, United States
Florida Cancer Specialists - EAST - SCRI - PPDS
West Palm Beach, Florida, United States
NYU Langone Hospital - Long Island
Mineola, New York, United States
NYU Cancer Center
New York, New York, United States
Mount SInai Medical Center
New York, New York, United States
MD Anderson Cancer Center
Houston, Texas, United States
Oncology & Hematology Associates of Southwest Virginia, Inc
Blacksburg, Virginia, United States
Virginia Oncology Associates
Norfolk, Virginia, United States
Hospital Britanico
Buenos Aires, , Argentina
Clinica Adventista Belgrano
Ciudad Autonoma Buenos Aires, , Argentina
Centro Oncologico Riojano Integral (CORI)
La Rioja, , Argentina
Concord Repatriation General Hospital
Concord, New South Wales, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia
Alfred Health
Melbourne, Victoria, Australia
Cliniques Universitaires St-Luc
Brussels, , Belgium
Jessa Zkh (Campus Virga Jesse)
Hasselt, , Belgium
Clinique Ste-Elisabeth
Namur, , Belgium
AZ Delta (Campus Rumbeke)
Roeselare, , Belgium
Hospital de Cancer de Barretos
Barretos, São Paulo, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP
São Paulo, São Paulo, Brazil
Ottawa Hospital Regional Cancer Centre
Ottawa, Ontario, Canada
Princess Margaret Cancer Center
Toronto, Ontario, Canada
Jewish General Hospital
Montreal, Quebec, Canada
Hunan Cancer Hospital
Changsha, , China
Harbin Medical University Cancer Hospital
Harbin, , China
Shanghai Pulmonary Hospital
Shanghai, , China
Rambam Medical Center
Haifa, , Israel
Rabin MC
Petah Tikva, , Israel
Tel Aviv Sourasky Medical Ctr
Tel Aviv, , Israel
Istituto Nazionale Tumori Fondazione G. Pascale
Napoli, Campania, Italy
Policlinico Universitario Agostino Gemelli IRCCS
Rome, Lazio, Italy
Irccs Istituto Nazionale Dei Tumori (Int)
Milan, Lombardy, Italy
A.O. Universitaria S. Luigi Gonzaga
Orbassano, Piedmont, Italy
National Cancer Center Hospital East
Chiba, , Japan
Kindai University Hospital
Osaka, , Japan
National Cancer Center Hospital
Tokyo, , Japan
The Cancer Institute Hospital of JFCR
Tokyo, , Japan
Wakayama Medical University Hospital
Wakayama, , Japan
NKI The Netherlands Cancer Institute
Amsterdam, , Netherlands
UMC St Radboud
Nijmegen, , Netherlands
Uniwersyteckie Centrum Kliniczne
Gda?sk, , Poland
Krakowski Szpital Specjalistyczny im sw. Jana Paw?a II
Krakow, , Poland
Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie
Olsztyn, , Poland
Pusan National University Hospital
Busan, , South Korea
Seoul National University Hospital
Seoul, , South Korea
Asan Medical Center
Seoul, , South Korea
Samsung Medical Center
Seoul, , South Korea
Korea University Guro Hospital
Seoul, , South Korea
ICO Badalona-H.U. Germans Trias i Pujol
Badalona, Barcelona, Spain
Vall d?Hebron Institute of Oncology (VHIO), Barcelona
Barcelona, , Spain
Hospital General Universitario Gregorio Marañon
Madrid, , Spain
Hospital Universitario 12 de Octubre
Madrid, , Spain
Hospital Universitario Virgen del Rocio
Seville, , Spain
Hospital Clinico Universitario de Valencia
Valencia, , Spain
Sahlgrenska University Hospital
Gothenburg, , Sweden
Universitätsspital Basel
Basel, , Switzerland
Inselspital Bern
Bern, , Switzerland
Taichung Veterans General Hospital
Taichung, , Taiwan
National Cheng Kung University Hospital
Tainan, , Taiwan
National Taiwan Uni Hospital
Taipei, , Taiwan
Chang Gung Medical Foundation - Linkou
Taoyuan District, , Taiwan
Beatson West of Scotland Cancer Centre
Glasgow, , United Kingdom
Barts & London School of Med
London, , United Kingdom
Countries
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Central Contacts
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Reference Study ID Number: BO44426 https://forpatients.roche.com/
Role: CONTACT
Phone: 888-662-6728 (U.S. and Canada)
Email: [email protected]
Other Identifiers
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2022-003048-28
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
2023-507171-22-00
Identifier Type: CTIS
Identifier Source: secondary_id
BO44426
Identifier Type: -
Identifier Source: org_study_id