The study medicine, PF-08634404, is a bispecific antibody drug that was designed to target both PD-1 and VEGF. This dual mechanism has the potential to achieve tumor immunosurveillance, while disrupting vascular support for tumor progression, compared with blocking either target alone in patients with solid tumors.

Preliminary clinical data with PF-08634404 as a single agent and combined with chemotherapy have demonstrated clinically meaningful antitumor activity and a manageable safety profile in participants with other first-line locally advanced or metastatic solid tumors.

Nivolumab in combination with chemotherapy is commonly used as first-line standard of care treatment for certain gastroesophageal cancers.

• Aged 18 years or older
• Have treatment-naïve, locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma
• Have a HER2-negative status based on local testing results
• Have tumors that express PD-L1 based on local testing results
• Have at least one measurable lesion per RECIST 1.1 (for Phase 3, must have at least one evaluable lesion)
• Do not have squamous cell or undifferentiated gastroesophageal cancer
• Do not have a known DPD deficiency
• Only prior treatment in the peri-operative setting is allowed with an approved PD-1 or PD-L1 inhibitor, if the treatment was completed > 9 months prior to the time of enrollment.

DPD, dihydropyrimidine dehydrogenase; HER2, human epidermal growth factor receptor 2; PD-L1, programmed cell death ligand 1; RECIST 1.1; Response Evaluation Criteria in Solid Tumors Version 1.1; VEGF, vascular endothelial growth factor

_{Additional requirements apply. Only Principal Investigators can determine eligibility.}

Study endpoints

Phase 2

Primary endpoint

• Confirmed ORR using RECIST 1.1 as assessed by investigator
• AEs as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), timing, seriousness, and relationship to study intervention

Key secondary endpoints

• DOR and PFS using RECIST 1.1 as assessed by investigator
• OS
• Laboratory test abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing

Phase 3

Primary endpoint

• PFS using RECIST 1.1 as assessed by BICR
• OS

Key secondary endpoints

• ORR, PFS, and DOR using RECIST 1.1 as assessed by BICR and investigator
• PFS2 (PFS after next-line therapy) by investigator
• AEs as characterized by type, frequency, intensity (as graded by NCI CTCAE v5.0), timing, seriousness, and relationship to study intervention(s)
• Laboratory test abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing

Note: This is not a complete list of study endpoints.

•  AEs, adverse events; BICR, blinded independent central review; DOR, duration of response; NCI CTCAE v5.0, National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PFS2, PFS on next line therapy; RECIST 1.1; Response Evaluation Criteria in Solid Tumors version 1.1; VEGF, vascular endothelial growth factor