A Study of BLYG8824A in Participants With Locally Advanced or Metastatic Colorectal Cancer

Inclusion Criteria: * ECOG performance status of 0 or 1 * Life expectancy of at least 12 weeks * Histologically or cytologically documented invasive CRC: incurable, unresectable, locally advanced or metastatic CRC previously treated with multimodality therapy or mCRC * Locally advanced or metastatic CRC that has relapsed or is refractory to established therapies * Prior disease progression (or intolerance) following oxaliplatin, irinotecan, fluoropyrimidines, and anti-EGFR monoclonal antibodies * An archival tissue specimen or fresh baseline biopsy (when archival is not available) is required for enrollment into the study * Measurable disease, according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Non-measurable evaluable disease is acceptable for dose-escalation. * Adequate hematologic and end organ function * Acute, clinically significant treatment-related toxicity from prior therapy resolved to Grade ≤ 1 prior to study entry Expansion Cohort-Specific Inclusion Criteria * MSS or MSI-L disease as determined by polymerase chain reaction (PCR) and/or IHC * Measurable disease by RECIST v1.1 with at least one measurable target lesion in the expansion cohort * Progression must have occurred during or after most recent treatment for locally advanced or metastatic colorectal cancer * For patients enrolled in either a dedicated biopsy cohort or other expansion cohorts where biopsy is clinically feasible, willingness to consent to mandatory fresh pretreatment and on-treatment biopsies of safely accessible tumor lesions Exclusion Criteria: * Pregnant or breastfeeding, or intending to become pregnant during the study or within 4 months after the final dose of BLYG8824A * Significant cardiopulmonary dysfunction * Known clinically significant liver disease * Positive serologic or PCR test results for acute or chronic HBV infection * Acute or chronic HCV infection * HIV seropositivity * Poorly controlled Type 2 diabetes mellitus * Current treatment with medications that are well known to prolong the QT interval * Primary CNS malignancy, untreated CNS metastases, or active CNS metastases * Leptomeningeal disease * Spinal cord compression that has not been definitively treated with surgery and/or radiation * History of autoimmune disease * Prior allogeneic stem cell or solid organ transplantation