This study is being done to learn more about a new medicine called PF-08634404 and how well it works when given with chemotherapy to people with gastroesophageal cancer that is 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 gastric, gastroesophageal junction or esophageal adenocarcinoma Be treatment naïve for advanced or metastatic disease Be in good physical condition and have healthy organs based on medical tests.

The study has two parts:

• In the first part, researchers will check how safe the study medicine in combination with chemotherapy is and how well people respond to it.
• In the second part, they will compare study medicine plus chemotherapy to another approved treatment (nivolumab plus chemotherapy) to see which works better.

The treatment will be given in repeated time periods called cycles.

Inclusion Criteria:

• Histological or cytological confirmed gastric, gastroesophageal junction or esophageal adenocarcinoma.
• Evidence of locally advanced or metastatic disease.
• Eastern Cooperative Oncology Group performance status (ECOG) 0-1
• No prior systemic therapy for advanced or metastatic disease.
• Adequate hepatic, liver, and renal function
• HER-2 negative status based on local testing
• PD-L1 positive status based on local testing

Exclusion Criteria:

• Participants with known active CNS metastases, including leptomeningeal, 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.

Phase 2 is open-label, whereas Phase 3 is double-blind, randomized design