A Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib in Combination with Other Anti-Cancer Therapies in Patients with Previously Untreated Advanced or Metastatic Non-Small Cell Lung Cancer with a KRAS G12C Mutatio
- Conditions
- ntreated Advanced or Metastatic Non-Small Cell Lung CancerMedDRA version: 21.1Level: PTClassification code: 10059515Term: Non-small cell lung cancer metastatic Class: 100000004864MedDRA version: 21.1Level: PTClassification code: 10061873Term: Non-small cell lung cancer Class: 100000004864Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-507171-22-00
- Lead Sponsor
- F. Hoffmann-La Roche AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 166
Histologically or cytologically documented locally advanced unresectable or metastatic non-squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy, No prior systemic treatment for advanced unresectable or metastatic NSCLC, Confirmation of Biomarker eligibility: – Valid results from either central testing of tissue or local testing of blood or tissue documenting the presence of the KRAS G12C mutation – Valid results from either central or local testing of tissue documenting expression of PD-L1. For Cohort A, PD-L1 tumor cell expression >= 1% is required to be eligible. Patients in Sweden are required to have documented history of PD-L1 tumor cell expression =50%. For Cohort B, PD-L1 tumor cell expression is not required to be eligible. Local testing of tumor tissue for PD-L1 expression must be performed at an appropriately accredited/certified laboratory, Pretreatment 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, Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Known concomitant second oncogenic driver with available targeted treatment, 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 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, 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the safety and tolerability of divarasib in combination with pembrolizumab (Cohort A) and divarasib in combination with pembrolizumab plus platinum-based chemotherapy and pemetrexed (Cohort B);Secondary Objective: To evaluate the activity of divarasib in combination with pembrolizumab (Cohort A) and divarasib in combination with pembrolizumab plus platinum-based chemotherapy and pemetrexed (Cohort B), To evaluate the tolerability of divarasib in combination with pembrolizumab (Cohort A) and divarasib in combination with pembrolizumab plus platinum-based chemotherapy and pemetrexed (Cohort B), To characterize the divarasib PK profile, To identify a recommended dose of divarasib in combination regimens with pembrolizumab (Cohort A) and pembrolizumab plus platinum-based chemotherapy and pemetrexed (Cohort B);Primary end point(s): 1. Occurrence of adverse events, 2. Change from baseline at each visit in targeted safety parameters
- Secondary Outcome Measures
Name Time Method