1L NSCLC with KRAS G12C positive
Conditions
Interventions
Divarasib: Divarasib will be administered orally QD
Sponsors
Raymond Meng
Eligibility
Sex/Gender
All
Inclusion criteria
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
Exclusion criteria
Exclusion criteria: - Known concomitant second oncogenic driver with available targeted treatment - Squamous cell histology NSCLC - Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety - Percentage of Participants with Adverse Events | — |
Secondary
| Measure | Time frame |
|---|---|
| safety, efficacy, phamacokinetics - Objective Response Rate (ORR) - Duration of Response (DOR) - Progression-Free Survival (PFS) - Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Side Effects as Assessed Through the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) - Change from Baseline in Symptomatic Side Effects, as Assessed Through use of the PRO-CTCAE - Percentage of Participants Reporting "Frequent" or "Almost Constant" Diarrhea During the First Three Cycles of Treatment According to the PRO-CTCAE Criteria - Percentage of Participants Reporting "Severe" or "Very Severe" Nausea or Vomiting During the First Three Cycles of Treatment According to the PRO-CTCAE - Frequency of Participant's Response of the Degree they are Troubled with Treatment Symptoms, as Assessed Through use of the Single-item European Organisation for Research and Treatment of Cancer (EORTC) Item List 46 (IL46) - Plasma Concentration of Divarasib at Specified Timepoints - Identification of Divarasib Recommended Dose | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Israel, Italy, Japan, Netherlands, Poland, Republic of Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical trials information
Chugai Pharmaceutical Co., Ltd.
Outcome results
None listed