A Study to Investigate Efficacy and Safety of Cobimetinib Plus Atezolizumab and Atezolizumab Monotherapy Versus Regorafenib in Participants With Metastatic Colorectal Adenocarcinoma (COTEZO IMblaze370)

Disease-specific inclusion criteria:

• Histologically confirmed adenocarcinoma originating from the colon or rectum (Stage 4 American Joint Committee on Cancer [AJCC] 7th edition)
• Experienced disease progression or was intolerant to at least two systemic chemotherapy regimens for metastatic colorectal cancer that must have included fluroropyrimidines, irinotecan, and oxaliplatin; adjuvant regimen can be considered as one chemotherapy regimen for metastatic disease if the participant had disease recurrence within 6 months of completion; disease progression must have occurred within 3 months of the last systemic therapy administration

General inclusion criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Anticipated life expectancy greater than or equal to (>=) 3 months
• Adequate hematologic and end organ function
• Women of childbearing potential must agree to appropriately use an effective form of contraception (failure rate of less than [<] 1 percent [%] per year) during the treatment period, within 5 months after the last dose of atezolizumab, and within 3 months after the last dose of cobimetinib and regorafenib
• Men must agree not to donate sperm or have intercourse with a female partner without using appropriate barrier contraception during the treatment period and for 3 months after the last dose of either cobimetinib or regorafenib
• Provide an archival or newly obtained tumor tissue sample

• After the approximate 5% cap for microsatellite (MSI)-high participants is reached, only MSI-stable participants will be eligible
• Once the 50% cap for wild-type RAS has been reached, only extended RAS-mutant participants will be eligible
• Major surgery or radiotherapy within 21 days prior to Cycle 1 Day 1 or anticipation of needing such procedure while receiving study treatment
• Treatment with any anti-cancer agent within 14 days prior to Cycle 1 Day 1
• Uncontrolled tumor-related pain. Participants requiring narcotic pain medication must be on a stable regimen at study entry
• Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage more than once every 28 days. Indwelling drainage catheters (e.g., PleurX®) are allowed
• Active or untreated central nervous system (CNS) metastases are excluded
• Prior therapy with any cancer immunotherapy, MEK inhibitor, or regorafenib
• Participants with active malignancy (other than CRC) or a prior malignancy within the past 3 years are excluded. Participants with completely resected cutaneous melanoma (early stage), basal cell carcinoma, cutaneous squamous cell carcinoma, cervical carcinoma in-situ, breast carcinoma in-situ, and localized prostate cancer are eligible
• Unstable angina, new onset angina within last 3 months, myocardial infarction within last 6 months and current congestive heart failure New York Heart Association Class II or higher
• Left ventricular ejection fraction (LVEF) below institutional lower limit of normal or below 50%, whichever is lower
• Poorly controlled hypertension, defined as a blood pressure consistently above 150/90 millimeters of Mercury (mmHg) despite optimal medical management
• Human immunodeficiency virus (HIV) infection
• Active tuberculosis infection
• Severe infections within 2 weeks prior to Cycle 1 Day 1
• Active or chronic viral hepatitis B or C infection
• History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for central serous retinopathy, retinal vein occlusion, or neovascular macular degeneration
• Participants will be excluded if they currently have any of the risk factors as defined in the study protocol for retinal vein occlusion
• History of autoimmune disease
• History of idiopathic pulmonary fibrosis, organizing pneumonia, bronchiolitis obliterans, drug-induced pneumonitis, or idiopathic pneumonitis
• History of organ transplantation including allogeneic bone marrow transplantation
• Inability to swallow medications
• Malabsorption condition that would alter the absorption of orally administered medications
• Pregnant, lactating, breastfeeding, or intending to become pregnant during the study
• Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation of a live attenuated vaccine will be required during the study