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
Purpose
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).
Conditions
- Non-Small Cell Lung Cancer
- KRAS G12C Lung Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts 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
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Divarasib + Pembrolizumab |
Participants will receive divarasib orally, once daily (QD) and pembrolizumab via intravenous (IV) infusion every 3 weeks (Q3W) |
|
|
Active Comparator Pembrolizumab + Pemetrexed + Carboplatin or Cisplatin |
Participants will receive pembrolizumab, pemetrexed and carboplatin or cisplatin via IV infusion Q3W |
|
Recruiting Locations
Anchorage, Alaska 99508
Goodyear, Arizona 85338
Greenbrae, California 94904
Newport Beach, California 92658
Palo Alto, California 94301
Roseville, California 95661
San Francisco, California 94115
Colorado Springs, Colorado 80909
Fort Collins, Colorado 80528
Hartford, Connecticut 06102-5037
Fort Myers, Florida 33901-8108
Gainesville, Florida 32610
Hialeah, Florida 33013
Hollywood, Florida 33021
Miami, Florida 33136
Pensacola, Florida 32504
St. Petersburg, Florida 33701
West Palm Beach, Florida 33401-3406
Atlanta, Georgia 30318
Newnan, Georgia 30265
Savannah, Georgia 31405
Boise, Idaho 83712
Chicago Ridge, Illinois 60415
Zion, Illinois 60099
Des Moines, Iowa 50309
Iowa City, Iowa 52242
Baltimore, Maryland 21229-5201
Boston, Massachusetts 02114
Farmington Hills, Michigan 48334
St Louis, Missouri 63131
Lincoln, Nebraska 68506
Reno, Nevada 89511
Farmington, New Mexico 87401
The Bronx, New York 10461
Westbury, New York 11590
Pinehurst, North Carolina 28374
Columbus, Ohio 43210
Portland, Oregon 97239
Bethlehem, Pennsylvania 18015
Pittsburgh, Pennsylvania 15212
West Reading, Pennsylvania 19611
Memphis, Tennessee 38120
El Paso, Texas 79915
Fort Worth, Texas 76104
Houston, Texas 77030-4000
Kingwood, Texas 77339
Lubbock, Texas 79415
The Woodlands, Texas 77380
Tyler, Texas 75708
Norfolk, Virginia 23502
More Details
- Status
- Recruiting
- Sponsor
- Hoffmann-La Roche
Study Contact
Reference Study ID Number: CO45042 https://forpatients.roche.com/ No attachments to email below.888-662-6728 (U.S. and Canada)
global-roche-genentech-trials@gene.com