A Study Evaluating the Efficacy and Safety of Divarasib and Pembrolizumab Versus Pembrolizumab and Pemetrexed and Carboplatin or Cisplatin in Participants With Previously Untreated, KRAS G12C-Mutated, Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer
Divarasib: Divarasib will be administered orally QD
Pembrolizumab: Pembrolizumab will be administered via IV infusion Q3W
Pemetrexed: Pemetrexed will be administered via IV infusion Q3W
Carboplatin: Carboplatin will be administered via IV infusion Q3W
Cisplatin: Cisplatin will be administered via IV infusion Q3W
Study summary
The purpose of this study is to evaluate the efficacy and safety of divarasib and pembrolizumab compared with pembrolizumab and pemetrexed and carboplatin or cisplatin, for the first-line treatment of adult participants with KRAS G12C-mutated, advanced or metastatic non squamous non-small cell lung cancer (NSCLC).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Histologically or cytologically confirmed diagnosis of advanced or metastatic non squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy
* Measurable disease, as defined by RECIST v1.1
* No prior systemic treatment for advanced or metastatic NSCLC
* Documentation of the presence of a KRAS G12C mutation
* Documentation of known PD-L1 expression status in tumor tissue
* Availability of a representative tumor specimen
* Adequate end-organ function
* Eligible to receive a platinum-based chemotherapy regimen
Exclusion Criteria Related to NSCLC:
* Known concomitant second oncogenic driver with available targeted treatment
* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
* Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for \>=2 weeks prior to randomization
* History of leptomeningeal disease
* Uncontrolled tumor-related pain
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once a month or more frequently)
Exclusion Criteria Related to Current or Prior Treatments:
* Any anti-cancer systemic therapy, including hormonal therapy, within 21 days prior to randomization, or is expected to require any other form of antineoplastic therapy while in the study
* Radiation therapy including palliative RT to bone metastases within 2 weeks prior to randomization and RT to the lung \>30Gy within 6 months prior to randomization
* Prior treatment with KRAS G12C inhibitors or pan-KRAS/RAS inhibitors
* Treatment with systemic immunosuppressive or immunostimulatory medications, including CD137 agonists and immune checkpoint inhibitors
* Current treatment with medications that are well known to prolong the QT interval
* Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to randomization
* Prior allogeneic stem cell or solid organ transplantation
Exclusion Criteria Related to General Health:
* History of malignancy other than NSCLC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival \[OS\] rate \>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
* Individuals with chronic diarrhea, short bowel syndrome or significant upper gastrointestinal surgery including gastric resection, a history of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) or any active bowel inflammation (including diverticulitis), malabsorption syndrome, conditions that would interfere with enteral absorption
* History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on the screening chest computed tomography scan
* Significant cardiovascular disease within 3 months prior to screening
Primary outcome measure(s)
Progression-Free Survival (PFS) — Up to approximately 5 years PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by blinded independent central review (BICR) according to RECIST v1.1, or death from any cause (whichever occurs first)
Overall Survival (OS) — Up to approximately 5 years OS is defined as the time from randomization to death from any cause
Trial sites (280)
Facility
City
Region
Status
Alaska Oncology and Hematology
Anchorage
Alaska
Recruiting
City of Hope - Phoenix
Goodyear
Arizona
Recruiting
Community Cancer Institute (CCI)
Clovis
California
Recruiting
Marin Cancer Care Inc
Greenbrae
California
Recruiting
UCI Health-CIACC
Irvine
California
Recruiting
UCLA Oncology Center
Los Angeles
California
Recruiting
Hoag Memorial Hospital
Newport Beach
California
Recruiting
University of California Irvine
Orange
California
Recruiting
Palo Alto Medical Foundation Research Center
Palo Alto
California
Recruiting
Sutter Institute for Medical Research
Roseville
California
Recruiting
California Pacific Medical Center
San Francisco
California
Recruiting
UC Health Oncology Research
Colorado Springs
Colorado
Recruiting
Poudre Valley Health Care, Inc. d/b/a Poudre Valley Health System
Fort Collins
Colorado
Recruiting
Hartford Hospital
Hartford
Connecticut
Recruiting
Florida Cancer Specialists - SOUTH - SCRI - PPDS
Fort Myers
Florida
Recruiting
University of Florida Health at Shands
Gainesville
Florida
Recruiting
BioResearch Partner
Hialeah
Florida
Recruiting
Memorial Healthcare System - Memorial Regional Hospital
Hollywood
Florida
Recruiting
Sylvester Comprehensive Cancer Center
Miami
Florida
Recruiting
Ascension Sacred Heart
Pensacola
Florida
Recruiting
Florida Cancer Specialists - NORTH - SCRI - PPDS
St. Petersburg
Florida
Recruiting
Florida Cancer Specialists - EAST - SCRI - PPDS
West Palm Beach
Florida
Recruiting
Piedmont Cancer Institute, PC
Atlanta
Georgia
Recruiting
City of Hope® Atlanta
Newnan
Georgia
Recruiting
Summit Cancer Care PC
Savannah
Georgia
Recruiting
St. Luke's Cancer Institute
Boise
Idaho
Recruiting
Affiliated Oncologists, LLC
Chicago Ridge
Illinois
Recruiting
Hope and Healing Cancer Services
Hinsdale
Illinois
Withdrawn
City of Hope® Cancer Center Chicago
Zion
Illinois
Recruiting
Mission Cancer + Blood - IMMC
Des Moines
Iowa
Recruiting
University of Iowa
Iowa City
Iowa
Recruiting
Saint Agnes Hospital - Baltimore - Hunt - PPDS
Baltimore
Maryland
Recruiting
Walter Reed National Military Medical Center
Bethesda
Maryland
Recruiting
Massachusetts General Hospital
Boston
Massachusetts
Recruiting
University of Massachusetts Memorial Medical Center
Worcester
Massachusetts
Recruiting
Profound Research, LLC
Farmington Hills
Michigan
Recruiting
Missouri Baptist Medical Center
St Louis
Missouri
Recruiting
NHO Revive Research Institute
Lincoln
Nebraska
Recruiting
Cancer Care Specialists
Reno
Nevada
Recruiting
San Juan Oncology Associates
Farmington
New Mexico
Recruiting
+ 240 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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