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.
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.
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.
Parallel
PF-08634404
Biological/VaccineParticipants will receive PF-08634404 intravenously.
Chemotherapy
DrugParticipants will receive PF-08634404 intravenously in combination with Chemotherapy.
Nivolumab
Biological/VaccineParticipants will receive Nivolumab intravenously.
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.
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.
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.
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.
Phase 2: Duration of Response (DOR) using RECIST 1.1 as assessed by investigator
DOR by investigator is defined as the time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the date of first documented disease progression per RECIST 1.1 as assessed by investigator, respectively, or death due to any cause, whichever occurs first.
Phase 2: Progression Free Survival (PFS) using RECIST 1.1 as assessed by investigator
PFS by investigator is defined as the time from the date of first dose to the date of first documented disease progression per RECIST 1.1 as assessed by investigator, or death due to any cause, whichever occurs first.
Phase 2: Overall Survival (OS)
OS is defined as the time from the date of first dose to the date of death due to any cause.
Phase 2: Number of participants with laboratory abnormalities
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing. For laboratory tests without CTCAE grade definitions, results will be categorized as normal, high, low, or not done and be listed.