A Randomized, Double-Blind, Phase 3 Study of Standard-of-Care Chemotherapy and Bevacizumab With or Without INCA33890 in the First-Line Treatment of Metastatic Microsatellite Stable Colorectal Cancer

Prior treatment

• Significant concurrent and/or uncontrolled medical condition as detailed in the protocol
• Medications: 19. Current use of chronic systemic corticosteroids (ie, > 10 mg/day of prednisone or equivalent).
• Received a live vaccine within 28 days before the first dose of study treatment.
• Current use of prohibited medication as defined in the protocol.
• Tumor known to invade or encase a major blood vessel or any history of clinically significant bleeding from tumor lesions within 30 days before enrollment.
• Treatment with an anti–PD-(L)1 or anti–CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways, for any indication within the past 3 years.
• Toxicity from prior therapy that has not recovered to ≤ Grade 1 or baseline. Paresthesia and/or peripheral sensory neuropathy of Grade 2 or higher due to prior chemotherapy (eg, oxaliplatin) are exclusionary.
• Concurrent anticancer therapy other than the therapies being tested in this study.
• Received thoracic radiation of > 30 Gy within 6 months of the first dose of study treatment.

Other illness

• Cancer History: Known MSI-H/dMMR status per local standard of practice as obtained from historical data in the participant's medical record.
• Medical History: History of organ transplant, including allogeneic stem cell transplantation.
• Active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy is allowed.
• Uncontrolled active HBV or HCV infection.
• History of other malignancy within 2 years of study entry.

Lab values

• HIV positive, unless all of the following criteria are met: a. CD4+ count ≥ 350 μL. b. Undetectable viral load. c. Receiving highly active antiretroviral therapy.

Other

• Known complete DPD deficiency as reported in the participant's medical record. Local guidelines and regulations for DPD activity testing and dose adjustments should be applied in case of partial deficiency.
• BRAF V600E mutation as obtained from historical data in the participant's medical record.
• Untreated and/or progressing CNS metastases (eg, evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain or CNS metastases).

• Ability to comprehend and willingness to sign a written ICF for the study.
• Aged 18 years or older, inclusive, at the time of signing the ICF.
• Histologically or cytologically confirmed metastatic colorectal adenocarcinoma (Stage IV per the American Joint Committee on Cancer, Cancer Staging Manual, 8th Edition) not amenable to curative resection.
• No prior systemic treatment for unresectable or metastatic CRC. Participants who previously received neoadjuvant and/or adjuvant therapy are allowed to enroll if there was no recurrence of disease within 12 months of last systemic therapy administration.
• Radiographically measurable disease (based on local site investigator/radiology evaluation) per RECIST v1.1 criteria.
• Adequate organ function as defined in the protocol
• Willingness to avoid pregnancy or fathering children.