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
Recruiting · NCT05789082 · Interventional (participants receive a specific treatment)
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
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).
Who can take part
Age range
18 Years and older
Sex
All (male and female)
Healthy volunteers
No - a diagnosis or condition is required
Phase
Phase 1, Phase 2
Study type
Interventional (participants receive a specific treatment)
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
Where it is running
60 locations listed across 6 US states.
- 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
- Montefiore Medical Center - Montefiore Medical Park - The Bronx, 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
- NKI The Netherlands Cancer Institute - Amsterdam, Netherlands
- Vall d?Hebron Institute of Oncology (VHIO), Barcelona - Barcelona, Spain
- Universitätsspital Basel - Basel, Switzerland
- Inselspital Bern - Bern, Switzerland
- Cliniques Universitaires St-Luc - Brussels, Belgium
- Hospital Britanico - Buenos Aires, Argentina
- Pusan National University Hospital - Busan, South Korea
- Hunan Cancer Hospital - Changsha, China
- National Cancer Center Hospital East - Chiba, Japan
- Clinica Adventista Belgrano - Ciudad Autonoma Buenos Aires, Argentina
- Uniwersyteckie Centrum Kliniczne - Gda?sk, Poland
- Beatson West of Scotland Cancer Centre - Glasgow, United Kingdom
- Sahlgrenska University Hospital - Gothenburg, Sweden
- Rambam Medical Center - Haifa, Israel
- Harbin Medical University Cancer Hospital - Harbin, China
- Jessa Zkh (Campus Virga Jesse) - Hasselt, Belgium
- Krakowski Szpital Specjalistyczny im sw. Jana Paw?a II - Krakow, Poland
- Centro Oncologico Riojano Integral (CORI) - La Rioja, Argentina
- Barts & London School of Med - London, United Kingdom
- Hospital General Universitario Gregorio Marañon - Madrid, Spain
- Hospital Universitario 12 de Octubre - Madrid, Spain
- Clinique Ste-Elisabeth - Namur, Belgium
- UMC St Radboud - Nijmegen, Netherlands
- Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie - Olsztyn, Poland
- Kindai University Hospital - Osaka, Japan
- Rabin MC - Petah Tikva, Israel
- AZ Delta (Campus Rumbeke) - Roeselare, Belgium
- 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
- Hospital Universitario Virgen del Rocio - Seville, Spain
- Shanghai Pulmonary Hospital - Shanghai, China
- 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, Taiwan
- Tel Aviv Sourasky Medical Ctr - Tel Aviv, Israel
- National Cancer Center Hospital - Tokyo, Japan
- The Cancer Institute Hospital of JFCR - Tokyo, Japan
- Hospital Clinico Universitario de Valencia - Valencia, Spain
- Wakayama Medical University Hospital - Wakayama, Japan
- ICO Badalona-H.U. Germans Trias i Pujol - Badalona, Barcelona, Spain
- Istituto Nazionale Tumori Fondazione G. Pascale - Naples, Campania, Italy
Showing 60 of 71 listed sites. See the official record for the complete list.
Read the full protocol, contacts and eligibility on ClinicalTrials.gov →