Cobimetinib (Targeted Therapy) Plus Atezolizumab (Immunotherapy) in Participants With Advanced Melanoma Whose Cancer Has Worsened During or After Treatment With Previous Immunotherapy and Atezolizumab Monotherapy in Participants With Previously Untreated Advanced Melanoma

Inclusion criteria

Disease-Specific Inclusion Criteria: Cohorts A and B:

Histologically confirmed Stage IV (metastatic) or unresectable Stage IIIc BRAF V600 WT (locally advanced) melanoma
Documentation of BRAF V600 mutation-negative status in melanoma tumor tissue (archival [< 5 years old] or newly obtained) through use of a clinical mutation test approved by the local health authority
Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Disease progression on or after treatment with a programmed death (PD)-1 inhibitor either as monotherapy or in combination with other agent(s)

Additional Disease-Specific Inclusion Criteria in Cohort B (Biopsy Cohort):

Progressed on or after anti-PD-1 therapy within 12 weeks before study start
Received a minimum of two cycles of anti-PD-1 therapy
Meet the following criteria for resistance to an anti-PD-1 agent: primary resistance defined as disease progression, according to RECIST v1.1, as best response; secondary resistance defined as disease progression after initial confirmed response according to RECIST v1.1
Consent to undergo tumor biopsies of accessible lesions, before and during treatment and at radiographic progression, for biomarker analyses.
Have at least two accessible lesions that are amenable to excisional or core-needle (minimum three cores and minimum diameter 18 gauge; however, 16 gauge is desirable) biopsy without unacceptable risk of a major procedural complication. Exceptions may be made if patient has only one lesion that allows multiple biopsies.

Disease-Specific Inclusion Criteria: Cohort C:

Histologically confirmed Stage IV (metastatic) or unresectable Stage IIIc BRAFV600-WT (locally advanced) melanoma
Naive to prior systemic anti-cancer therapy for melanoma
Documentation of BRAFV600 mutation-negative status in melanoma tumor tissue (archival [< 5 years old] or newly obtained) 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.
Measurable disease according to RECIST v1.1.

General Inclusion Criteria:

Ability to comply with the study protocol, in the investigator's judgment
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Available and adequate baseline tumor tissue sample
Life expectancy ≥ 18 weeks
Adequate hematologic and end-organ function, defined by laboratory test results, obtained within 14 days before initiation of study treatment
For women of childbearing potential: abstinent or use an effective form of contraceptive method for at least 3 months for cobimetinib and at least 5 months for atezolizumab. Women must refrain from donating eggs during this same period.
For men: abstinent or use contraceptive measures and agreement to refrain from donating sperm for at least 3 months after cobimetinib and atezolizumab

Exclusion criteria

Prior treatment with a mitogen activated-protein kinase (MAPK) inhibitor
Ocular melanoma
Major surgical procedure other than for diagnosis within 4 weeks before initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study
Traumatic injury within 2 weeks before initiation of study treatment
Palliative radiotherapy within 14 days before initiation of study treatment
Active malignancy (other than BRAF V600 mutation-negative melanoma) or malignancy within 3 years
Treatment with any anti-cancer agent 14 days prior to Cycle, Day 1 other than aPD-1 based therapy
Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤ 1. Clinically stable patients with manageable immune-related adverse events resulting from prior cancer immunotherapy may be eligible for the study.
For Cohort C only: any prior anti-cancer therapy for advanced melanoma
History or evidence of ongoing serous retinopathy or retinal vein occlusion (RVO) at baseline
History of clinically significant cardiac dysfunction
Active or untreated central nervous system (CNS) metastases
History of metastases to brain stem, midbrain, pons, or medulla, or within 10 millimeter (mm) of the optic apparatus (optic nerves and chiasm)
History of leptomeningeal metastatic disease
Human immunodeficiency virus (HIV) infection
Active tuberculosis
Severe infection within 4 weeks before initiation of study treatment
Signs or symptoms of infection within 2 weeks before initiation of study treatment
Treatment with oral or intravenous (IV) antibiotics within 2 weeks prior to Day 1 of Cycle 1
Active or chronic viral hepatitis B or C infection
Active or history of autoimmune disease or immune deficiency
Prior allogeneic stem cell or solid organ transplantation
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
Treatment with systemic immunosuppressive medications with the following exceptions:
Patients who have received acute, low-dose systemic immunosuppressant medication (≤ 10 mg/day oral prednisone or equivalent) or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Medical Monitor approval has been obtained.
Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
Current severe, uncontrolled systemic disease other than cancer
Any Grade >/=3 hemorrhage or bleeding event within 28 days of Day 1 of Cycle 1
History of stroke, reversible ischemic neurological defect, or transient ischemic attack within 6 months prior to Day 1
Anticipated use of any concomitant medication during or within 7 days before initiation of study treatment that is known to cause QT prolongation
Any psychological, familial, sociological, or geographic condition that may hamper compliance with the protocol and follow-up after treatment discontinuation
History of malabsorption or other clinically significant metabolic dysfunction that may interfere with absorption of oral study treatment
Pregnant or breastfeeding, or intending to become pregnant during the study
Known clinically significant liver disease
Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the participant at high risk for treatment complications
Treatment with a live, attenuated vaccine within 4 weeks before initiation of study treatment, or anticipation of need for such a vaccine during the course of the study
Known hypersensitivity to any component of the atezolizumab or cobimetinib formulations
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
Treatment with any other investigational agent or participation in another clinical study with therapeutic intent
Inability or unwillingness to swallow pills
Requirement for concomitant therapy or food that is prohibited during the study