The purpose of this study is to learn more about a new medicine called PF-08634404, and how well it works in people with cancer of the colon or rectum (CRC)). The goal is to understand if the new study medicine, combined with chemotherapy that is approved for colorectal cancer, can help people whose cancer has spread or returned after treatments taken before.

To join the study, participants must meet the following conditions:

• Be 18 years or older.
• Have colorectal cancer that has spread to other parts of your body.
• Be in good enough health to receive study treatment.
• Should not be pregnant before starting treatment.

Participants will be randomized (like flipping a coin) to one of 2 different treatment arms. The first arm (Arm A) will include the new medicine PF-08634404 in combination with chemotherapy that is approved for colorectal cancer, and the second arm (Arm B) will include an approved medicine for colorectal cancer, called Bevacizumab, in combination with chemotherapy that is approved for this type of cancer. Participants and their doctors will not know which arm they are being assigned to. Participants will receive all the study medications through intravenous (IV) infusions, which means the medicine is given directly into a vein. The treatment will be given in cycles, and participants may continue receiving it if it is helping and they are not experiencing serious side effects.

The medicine will be given at a clinical site, where trained medical staff will check participants during and after each treatment.

• The study is expected to last approximately 33 months for each participant.
• Participants will have regular visits to the study site for treatment, health checks, and tests.
• After stopping treatment, participants will return for a final visit about 30 to37 days later to check their health and review any side effects.
• Follow-up will continue every 12 weeks by phone or in person or by reviewing health records to check on health status and any new treatments.

Inclusion Criteria:

• Histological or cytological confirmed colorectal adenocarcinoma.
• Evidence of Stage IV metastatic disease.
• No prior systemic therapy for metastatic disease.
• Eastern Cooperative Oncology Group performance status (ECOG) 0-1
• At least one measurable lesion according to RECIST 1.1 per Investigator assessment.
• Adequate hepatic, liver, and renal function

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• Locally confirmed BRAF V600E mutation
• Locally confirmed microsatellite instability (MSI)-high or DNA mismatch repair deficiency (dMMR) colorectal cancer
• Participants with known active symptomatic CNS lesions, including leptomeningeal metastasis, brainstem, meningeal, or spinal cord metastases or compression
• Clinically significant risk of hemorrhage or fistula
• Major surgery or severe trauma within 4 weeks prior to the first dose, or planned major surgery during the study
• History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation
• Any Grade ≥3 bleeding/hemorrhage events within 28 days of Cycle 1 Day 1, or prior history of clinically significant bleeding events
• Clinically significant cardiovascular disease, or other comorbidities, within 6 months prior to first dose
• Participants with active autoimmune diseases requiring systemic treatment within the past 2 years
• Evidence of non-infectious or drug-induced interstitial lung disease (ILD) pneumonitis

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.