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
Sponsor: Hoffmann-La Roche
ClinicalTrials ID:NCT06793215
This study assesses the efficacy and safety of divarasib and pembrolizumab in treating KRAS G12C-mutated advanced NSCLC. Eligible participants must have an ECOG status of 0-1, measurable disease, and no prior systemic treatment. Exclusions include other oncogenic drivers and recent anti-cancer therapies. Interventions include oral divarasib and IV pembrolizumab, pemetrexed, carboplatin, or cisplatin.
Patient Parameters
| Parameter | Options |
|---|
Program Overview
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 Criteria
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
Locations
| FACILITY | ZIP | CITY | STATE |
|---|---|---|---|
| Alaska Oncology and Hematology | 99508 | Anchorage | Alaska |
| Marin Cancer Care Inc | 94904 | Greenbrae | California |
| BioResearch Partner | 33013 | Hialeah | Florida |
| Summit Cancer Care PC | 31405 | Savannah | Georgia |
| Hope and Healing Cancer Services | 60521 | Hinsdale | Illinois |
| Profound Research, LLC | 48334 | Farmington Hills | Michigan |
| Missouri Baptist Medical Center | 63131 | St Louis | Missouri |
| San Juan Oncology Associates | 87401 | Farmington | New Mexico |
| Clinical Research Alliance | 11590 | Westbury | New York |
| Baptist Cancer Center | 38120 | Memphis | Tennessee |
Get This Program In Your Inbox
You can sign up and apply your patients for this program.
