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

This is a Phase III, multicenter, open-label, three-arm, randomized study in participants with unresectable locally advanced or metastatic colorectal cancer (CRC) who have received at least two prior regimens of cytotoxic chemotherapy for metastatic disease. The study compares regorafenib, a standard of care therapy in this setting, to cobimetinib plus atezolizumab and atezolizumab monotherapy.


Eligibility Criteria:
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