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

- Disease progression during or following two (but not more) separate lines of treatment
for metastatic colorectal cancer (mCRC) that consisted of fluoropyrimidine-,
oxaliplatin-, or 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

- Mutation in the BRAF oncogene

- 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