RecruitingInterventionalPhase 2/Phase 3

A PHASE 2/3 INTERVENTIONAL STUDY OF PF-08634404 IN COMBINATION WITH CHEMOTHERAPY IN TREATMENT-NAÏVE PARTICIPANTS WITH LOCALLY ADVANCED OR METASTATIC GASTRIC, GASTROESOPHAGEAL JUNCTION, OR ESOPHAGEAL ADENOCARCINOMA

NCT ID: NCT07392892Sponsor: PfizerLast updated: 2026-06-12

Summary

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.

Arms & interventions

BiologicalPF-08634404
Participants will receive PF-08634404 intravenously.
DrugChemotherapy
Participants will receive PF-08634404 intravenously in combination with Chemotherapy.
BiologicalNivolumab
Participants will receive Nivolumab intravenously.

Outcome measures

Primary

Phase 2: Confirmed Objective response rate (ORR) using RECIST 1.1 as assessed by investigator
Confirmed ORR by investigator is defined as the proportion of participants with confirmed Complete Response (CR) or Partial Response (PR) per RECIST v1.1 as assessed by investigator.
Time frame: Approximately 4 years
Phase 2: Number of participants with treatment-emergent adverse events
Adverse Events (AEs) as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study intervention.
Time frame: Through 90 days after the last study intervention; Approximately 4 years
Phase 3: Progression Free Survival (PFS) using RECIST 1.1 as assessed by BICR
PFS by BICR is defined as the time from the date of randomization to the date of first documented disease progression per RECIST 1.1 as assessed by BICR, or death due to any cause, whichever occurs first.
Time frame: Approximately 4 years
Phase 3: Overall Survival (OS)
OS is defined as the time from the date of randomization to the date of death due to any cause.
Time frame: Approximately 4 years

Secondary

Phase 2: Duration of Response (DOR) using RECIST 1.1 as assessed by investigator
Time frame: Approximately 4 years
Phase 2: Progression Free Survival (PFS) using RECIST 1.1 as assessed by investigator
Time frame: Approximately 4 years
Phase 2: Overall Survival (OS)
Time frame: Approximately 4 years
Phase 2: Number of participants with laboratory abnormalities
Time frame: Through 90 days after the last study intervention; Approximately 4 years
Phase 2: Serum concentrations of PF-08634404
Time frame: Approximately 21 months
Phase 2: Incidence of Anti-Drug Antibody (ADA) against PF-08634404
Time frame: Approximately 21 months
Phase 3: ORR using RECIST 1.1 as assessed by BICR
Time frame: Approximately 4 years
Phase 3: ORR using RECIST 1.1 as assessed by investigator
Time frame: Approximately 4 years
Phase 3: Progression free survival (PFS) using RECIST 1.1 as assessed by investigator
Time frame: Approximately 4 years
Phase 3: DOR using RECIST 1.1 as assessed by BICR
Time frame: Approximately 4 years
Phase 3: DOR using RECIST 1.1 as assessed by investigator
Time frame: Approximately 4 years
Phase 3: PFS2 (PFS after next-line therapy) by investigator
Time frame: Approximately 4 years
Phase 3: Number of participants with treatment-emergent adverse events
Time frame: Through 90 days after the last study intervention; Approximately 4 years
Phase 3: Number of participants with laboratory abnormalities
Time frame: Through 90 days after the last study intervention; Approximately 4 years
Phase 3: Serum concentrations of PF-08634404
Time frame: Approximately 21 months
Phase 3: Incidence of ADA against PF-08634404
Time frame: Approximately 21 months
Phase 3: Change from baseline in Functional Assessment of Cancer Therapy - Gastric (FACT-Ga) Total score
Time frame: Approximately 4 years
Phase 3: Time to definitive deterioration in FACT-Ga Total score
Time frame: Approximately 4 years
Phase 3: Time to definitive deterioration in Gastric Cancer Subscale (GaCS) score
Time frame: Approximately 4 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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