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

Inclusion Criteria:

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

Exclusion Criteria:

- 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