A Study of Atezolizumab Plus Cobimetinib and Vemurafenib Versus Placebo Plus Cobimetinib and Vemurafenib in Previously Untreated BRAFv600 Mutation-Positive Patients With Metastatic or Unresectable Locally Advanced Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Atezolizumab; Atezolizumab Placebo; Cobimetinib; Vemurafenib; Vemurafenib Placebo
Intervention description: Will be administered as per the schedule described in individual arm.; Will be administered as per the schedule described in individual arm.; Will be administered as per the schedule described in individual arm.; Will be administered as per the schedule described in individual arm.; Will be administered as per the schedule described in individual arm.
Intervention MeSH terms: Atezolizumab; Vemurafenib; Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 514.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a Phase III, double-blinded, placebo-controlled, randomized, multicenter study
      designed to evaluate the efficacy, safety, and pharmacokinetics of atezolizumab + cobimetinib
      + vemurafenib compared with placebo + cobimetinib + vemurafenib in patients with previously
      untreated BRAFv600 mutation-positive metastatic or unresectable locally advanced melanoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Females of child bearing potential and males with female partners must and use of
             contraceptive methods with a failure rate of less than or equal to (</=)1% per year is
             required during treatment and for 6 months post treatment. Males should not expose
             pregnant partners to sperm and refrain from donating sperm for 6 months post
             treatment. Women must refrain from donating eggs during this same period

          -  Histologically confirmed Stage IV (metastatic) or unresectable Stage IIIc (locally
             advanced) melanoma

          -  Naive to prior systemic anti-cancer therapy for melanoma (example: chemotherapy,
             hormonal therapy, targeted therapy, immunotherapy, or other biologic therapies) except
             adjuvant treatment with interferon (IFN), interleukin (IL)-2, or vaccine therapies or
             herbal therapies

          -  Documentation of BRAFv600 mutation-positive status in melanoma tumor tissue (archival
             or newly obtained) through use of a clinical mutation test approved by the local
             health authority

          -  Eastern Cooperative Oncology Group Performance (ECOG) Status of 0 or 1

          -  Measurable disease according to RECIST v1.1 (must be outside central nervous system
             (CNS))

          -  Life expectancy >/=18 weeks

          -  For participants not receiving therapeutic anticoagulation: International normalized
             ratio (INR) or activated partial thromboplastin time (aPTT) less than or equal to
             (</=) 1.5*upper limit of normal (ULN) within 28 days prior to initiation of study
             treatment

          -  For participants receiving therapeutic anticoagulation: stable anticoagulant regimen
             and stable INR during the 28 days immediately preceding initiation of study treatment

        Exclusion Criteria:

        Cancer-Related Exclusion Criteria:

          -  Major surgical procedure within 4 weeks prior study treatment initiation

          -  Traumatic injury or palliative radiotherapy within 2 weeks prior study treatment
             initiation

          -  Active malignancy (other than BRAFv600 mutation-positive melanoma) or malignancy
             within 3 years prior to screening are excluded, with the exception of resected
             melanoma, resected basal cell carcinoma (BCC), resected cutaneous squamous cell
             carcinoma (SCC), resected carcinoma in situ of the cervix, resected carcinoma in situ
             of the breast, in situ prostate cancer, limited-stage bladder cancer, or any other
             curatively treated malignancies from which the participant has been disease-free for
             at least 3 years

        Ocular Exclusion Criteria:

          -  History of or evidence of retinal pathology on ophthalmologic examination that is
             considered a risk factor for neurosensory retinal detachment, central serous
             chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration

        Cardiac Exclusion Criteria:

          -  History of clinically significant cardiac dysfunction

          -  Left ventricular ejection fraction (LVEF) below the institutional lower limit of
             normal or below 50%

        Central Nervous System (CNS) Exclusion Criteria:

          -  Untreated or actively progressing CNS lesions (carcinomatous meningitis)

          -  History of metastases to brain stem, midbrain, pons, or medulla, or within 10
             millimeter (mm) of the optic apparatus (optic nerves and chiasm); or leptomeningeal
             metastatic disease; or intracranial hemorrhage

        Additional Exclusion Criteria:

          -  Uncontrolled diabetes or symptomatic hyperglycemia

          -  Current severe, uncontrolled systemic disease (including, but not limited to,
             clinically significant cardiovascular, pulmonary, or renal disease) other than cancer

          -  History of malabsorption or other clinically significant metabolic dysfunction

          -  Pregnant or breastfeeding, or intending to become pregnant during the study

          -  Prior allogeneic stem cell or solid organ transplantation

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia (example: bronchiolitis
             obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
             active pneumonitis on screening chest computed tomography (CT) scan

          -  Active or history of autoimmune disease or immune deficiency

          -  Known clinically significant liver disease, inherited liver disease and active viral
             disease

          -  Active tuberculosis

          -  Treatment with therapeutic oral or intravenous (IV) antibiotics; or with a live,
             attenuated vaccine; or systemic immunosuppressive medication

          -  Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovary
             cells or any component of the atezolizumab, cobimetinib, or vemurafenib formulations

          -  Any grade >/=3 hemorrhage or bleeding event within 4 weeks prior to initiation of
             study treatment

          -  History of stroke, reversible ischemic neurological defect, or transient ischemic
             attack within 6 months prior to initiation of study treatment