A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC)

Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Life expectancy ≥ 3 months, as determined by the investigator
* Histologically confirmed adenocarcinoma originating from the colon or rectum
* Metastatic disease not amenable to local treatment
* Disease progression during or following not more than two separate lines of treatment for metastatic colorectal cancer (mCRC) that consisted of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy in combination with a biologic agent
* Measurable disease (at least one target lesion) according to RECIST v1.1
* Adequate hematologic and end-organ function obtained within 14 days prior to initiation of study treatment

Exclusion Criteria:

* High microsatellite instability (MSI-H) tumor
* Presence of BRAFV600E mutation
* Prior treatment with any of the protocol-specified study treatments
* Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
* Biologic treatment within 2 weeks prior to initiation of study treatment, or other systemic treatment for CRC within 2 weeks or 5 half-lives of the drug (whichever is shorter) prior to initiation of study treatment
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* Eligibility only for the control arm
* Prior allogeneic stem cell or solid organ transplantation
* Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to the initiation of study treatment
* Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressant medication during study treatment
* Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab
* Current treatment with anti-viral therapy for HBV
* Uncontrolled pleural effusion, pericardial effusion, ascites requiring recurrent drainage procedures (once monthly or more frequently), or tumor related-pain,
* Uncontrolled or symptomatic hypercalcemia (ionized calcium \>1.5 mmol/L, calcium \>12 mg/dL, or corrected serum calcium \>ULN)
* Symptomatic, untreated, or actively progressing CNS metastases
* History of leptomeningeal disease
* Active or history of autoimmune disease or immune deficiency
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
* History of malignancy other than CRC within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
* Active tuberculosis
* Severe infection within 4 weeks prior to initiation of study treatment
* Significant cardiovascular disease
* Grade ≥3 hemorrhage or bleeding event within 28 days prior to initiation of study treatment
* Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
* History of severe allergic reactions to chimeric or humanized antibodies or fusion proteins
* Inability to swallow medications
* Malabsorption condition that would alter the absorption of orally administered medications
* Evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding
* Urine dipstick ≥ 2+ protein or ≥ 3.5 g of protein in a 24-hour urine collection