A Study of Cobimetinib Plus Atezolizumab Versus Pembrolizumab in Participants With Previously Untreated Advanced BRAFv600 Wild-Type Melanoma

Inclusion Criteria:

Disease-Specific Inclusion Criteria

- Histologically confirmed locally advanced and unresectable or metastatic melanoma

- Naive to prior systemic anti-cancer therapy for melanoma

- 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 still be eligible for the study, after discussion with and approval by
the Medical Monitor

- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
v1.1

- Age >=18 years at time of signing Informed Consent Form

- Ability to comply with the study protocol, in the investigator's judgment

- Histologically or cytologically confirmed BRAFV600 wild-type melanoma

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

- Life expectancy >=3 months

- Adequate hematologic and end-organ function

- For women of childbearing potential: agreement to remain abstinent or use at least two
forms of effective contraceptive with a failure rate of < 1% per year during the
treatment period and for at least 3 months after the last dose of cobimetinib and at
least 5 months after the last dose of atezolizumab or pembrolizumab

- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures (e.g. condom), and agreement to refrain from donating sperm,
for at least 3 months after the last dose of cobimetinib

- Willingness and ability of patients to report selected study outcomes (e.g., GHS and
HRQoL) using an electronic device or paper backup questionnaires.

Exclusion Criteria:

General Exclusion Criteria

- Inability to swallow medications

- Malabsorption condition that would alter the absorption of orally administered
medications

- Pregnancy, breastfeeding, or intention of becoming pregnant during the study

- History of severe hypersensitivity reactions to components of the cobimetinib,
atezolizumab, or pembrolizumab formulations

- Current or recent treatment with therapeutic antibiotics, live attenuated vaccines or
systemic immunostimulatory/immunosuppresive medication

- Any serious medical condition or abnormality in clinical laboratory tests that, in the
investigator's judgment, precludes the patient's safe participation in and completion
of the study Cancer-Related Exclusion Criteria

- Ocular melanoma

- Major surgery or radiotherapy within 21 days prior to Day 1 of Cycle 1 or anticipation
of needing such procedure while receiving study treatment

- Uncontrolled tumor-related pain

- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated
drainage more than once every 28 days

- Active or untreated central nervous system (CNS) metastases Exclusions Related to
Cardiovascular Disease

- Unstable angina, new-onset angina within last 3 months, myocardial infarction within
the last 6 months prior to Day 1 of Cycle 1, or current congestive heart failure
classified as New York Heart Association Class II or higher

- Left ventricular ejection fraction (LVEF) below institutional lower limit of normal or
<50%, whichever is lower

- Poorly controlled hypertension, defined as sustained, uncontrolled, non-episodic
baseline hypertension consistently above 159/99 mmHg despite optimal medical
management

- History or presence of an abnormal electrocardiogram (ECG) that is clinically
significant in the investigator's opinion, including complete left bundle branch
block, second- or third degree heart block, or evidence of prior myocardial infarction
Exclusions Related to Infections

- HIV infection

- Active tuberculosis infection

- Severe infections within 4 weeks prior to Day 1 of Cycle 1, including, but not limited
to, hospitalization for complications of infection, bacteremia, or severe pneumonia

- Signs or symptoms of clinically relevant infection within 2 weeks prior to Day 1 of
Cycle 1

- Treatment with oral or IV antibiotics within 2 weeks prior to Day 1 of Cycle 1

- Active or chronic viral hepatitis B or C infection Exclusions Related to Ocular
Disease

- Known risk factors for ocular toxicity Exclusions Related to Autoimmune Conditions and
Immunomodulatory Drugs

- Active or history of autoimmune disease or immune deficiency

- Prior allogeneic stem cell or solid organ transplantation

- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced or
idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan

- Treatment with systemic immunosuppressive medications within 2 weeks prior to Day 1,
Cycle 1 Exclusions Related to Other Medical Conditions or Medications

- Active malignancy (other than melanoma) or a prior malignancy within the past 3 years

- 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

- Proteinuria >3.5 gm/24 hr

- Consumption of foods, supplements, or drugs that are strong or moderate CYP3A4 enzyme
inducers or inhibitors at least 7 days prior to Day 1 of Cycle 1 and during study
treatment