The purpose of this study is to learn about the effects of study medicine (PF-08634404) when given alone or with another antibody (ipilimumab) for the treatment of a type of liver cancer called hepatocellular carcinoma (HCC) that is either locally advanced (spread to nearby tissues) or has spread to other parts of the body.

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

• Be 18 years or older.
• Have locally advanced or metastatic HCC.
• Is not a candidate for complete surgical or loco-regional therapies.
• Have not received any whole-body treatment for HCC.

Participants will receive PF-08634404 either alone or in combination with ipilimumab. The medicine will be given through intravenous (IV) infusions, which means it will be administered directly into a vein. All treatments will take place at clinical trial sites, where trained medical staff will monitor participants during and after each visit.

Inclusion Criteria:

• 18 years of age or older at screening.
• Locally advanced or metastatic HCC with diagnosis confirmed by histology/cytology or clinically by AASLD criteria (for patients with cirrhosis). Participants without cirrhosis require histological confirmation of diagnosis.
• Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and/or locoregional therapies.
• At least 1 measurable (as defined by RECIST 1.1 per investigator) and untreated lesion.
• Adequate hepatic, liver, and renal function
• No prior systemic therapy for HCC.
• ECOG performance status 0 or 1
• Child-Pugh Class A

Key Exclusion Criteria:

• Moderate or severe ascites.
• History of hepatic encephalopathy.
• Participants with known active CNS lesions, including leptomeningeal metastasis, brainstem, meningeal, or spinal cord metastases or compression.
• Clinically significant risk of hemorrhage or fistula.
• Participants with any history of another malignancy within 3 years.
• History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
• Participants with active autoimmune diseases requiring systemic treatment within the past 2 years.
• Clinically significant cardiovascular disease within 6 months prior to the first dose.
• Major surgery or severe trauma within 4 weeks prior to the first dose or planned major surgery during the study.
• History of severe bleeding tendency or coagulation dysfunction.
• History of severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding, including bleeding event due to esophageal and/or gastric varices, within 6 months prior to the first dose.
• Participants with acute, chronic or symptomatic infections.
• Participants with history of immunodeficiency.

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.