Untreated Advanced or Metastatic Non-Small Cell Lung Cancer MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: GDC-6036
Product Code: RO7435846
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: GDC-6036
Current Sponsor code: Ro 743-5846/F07
Other descriptive name: 1-((S)-4-((R)-7-(6-am
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - 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: .. Documented history of the KRAS G12C mutation .. Documented history of PD-L1 expression - For Cohort A, PD-L1 tumor cell expression >= 1% is required to be eligible - For Cohort B, PD-L1 tumor cell expression is not required to be eligible - 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 - Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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;Timepoint(s) of evaluation of this end point: 1-2. Until 60 days after the final dose of study treatment or until initiation of another anti-cancer therapy, whichever occurs first | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Objective response rate 2. Duration of response 3. Progression free survival 4. Presence, frequency of occurrence, severity, and/or degree of interference with daily function of symptomatic side effects as assessed through use of the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) 5. Change from baseline in symptomatic side effects, as assessed through use of the PRO-CTCAE 6. Proportion of participants reporting "frequent" or "almost constant" diarrhea during the first three cycles of treatment according to the PRO-CTCAE criteria 7. Proportion of participants reporting "severe" or "very severe" nausea or vomiting during the first three cycles of treatment according to the PRO-CTCAE 8. 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) 9. Plasma concentration of divarasib at specified timepoints 10. Recommended dose of divarasib in combination with pembrolizumab (Cohort A) or pembrolizumab plus platinum-based chemotherapy and pemetrexed (Cohort B) based on the totality of safety, activity, and PK data;Timepoint(s) of evaluation of this end point: 1-8. Up to 2 years 9. At Days 1, 8 and 15 of Cycles 1 and 2; Days 1 and 15 of Cycles 3 and 4; Day 1 of every other Cycle after Cycle 5 10. Up to 2 years | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Italy, Korea, Republic of, Mexico, Netherlands, Poland, Spain, Sweden, Switzerland, Taiwan, Türkiye, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed