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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
Trial Status: active
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).
Inclusion 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
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT06793215.