A phase III, open-label, multicenter, two-arm, randomized study to investigate the efficacy and safety of cobimetinib plus atezolizumab versus pembrolizumab in patients with previously untreated advanced BRAFv600 wild-type melanoma

INTERVENTION: The investigational medicinal products (IMPs) for this study are cobimetinib, atezolizumab, and pembrolizumab. Patients randomized to Arm A will receive cobimetinib 60 mg (three tablets of 20 mg each) by mouth QD on Days 1*21 of each 28‐day cycle. This 4‐week period is considered a treatment cycle. Cobimetinib should be taken at the same time every day. It can be taken with or without food. If a daily dose of cobimetinib is missed or if vomiting occurs when the dose is taken, resume dosing with the next scheduled dose. Patients randomized to Arm A will also receive atezolizumab 840 mg by IV infusion on Day 1 and Day 15 of each 28‐day cycle. This 4‐week period is considered a treatment cycle. Patients randomized to Arm B will receive 200 mg fixed‐dose of pembrolizumab by IV infusion Q3W as monotherapy. A 3‐week period is considered a treatment cycle. CONDITION: ; melanoma ; skin cancer 10040900 PRIMARY OUTCOME: Progression‐free survival, as measured by independent review; SECONDARY OUTCOME: 1. Overall survival ; 2. Two‐year landmark survival ; 3. Objective response rate ; 4. PFS, as determined by the investigator ; 5. Disease control rate ; 6. Duration of objective response as determined by indenpendent review ; 7. Duration of objective response as determined by the investigator ; 8. Change from baseline in HRQoL scores ; 9. Occurrence and severity of adverse events ; 10. Change from baseline in selected vital signs ; 11. Change from baseline in selected clinical laboratory test results ; 12. Plasma concentration of cobimetinib at specified timepoints ; 13. Serum concentration of atezolizumab at specified timepoints ; 14. Incidence of anti‐drug antibodies (ADAs) during the study relative to the ; prevalence of ADAs at baseline ; INCLUSION CRITERIA: Disease‐Specific Inclusion Criteria ‐ Histologically confirmed locally advanced and unresectable or metastatic melanoma ‐ Naive to prior systemic anti‐cancer therapy for melanoma with the following exeptions: * adjuvant treatment with IFN‐alpha, IL‐2 or vaccine therapies, if discontinued at least 28 days prior to initiation of study treatment * adjuvant treatment with ipilimumab, if discontinued at least 90 days prior to initiation of study treatment ‐ Documentation of BRAFV600 wild‐type status in melanoma tumor tissue through use of a clinical mutation test approved by the local health authority ‐ A representative, formalin‐fixed, paraffin‐embedded (FFPE) tumor specimen in a paraffin block (preferred) or 20 slides containing unstained, freshly cut, serial sections must be submitted along with an associated pathology report prior to study entry. If 20 slides are not available or the tissue block is not of sufficient size, the patient may s