Untreated Advanced or Metastatic Gastric, Gastroesophageal Junction , or Esophageal Adenocarcinoma, Metastatic Gastric Cancer, Gastroesophageal Junction Cancer, Esophageal Adenocarcinoma
Conditions
Keywords
gastric cancer, gastroesophageal junction cancer, esophageal adenocarcinoma
Brief 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.
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.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Phase 2 is open-label, whereas Phase 3 is double-blind, randomized design
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy 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
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Confirmed Objective response rate (ORR) using RECIST 1.1 as assessed by investigator | Approximately 4 years | 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 | Through 90 days after the last study intervention; Approximately 4 years | 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 | Approximately 4 years | 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) | Approximately 4 years | OS is defined as the time from the date of randomization to the date of death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Duration of Response (DOR) using RECIST 1.1 as assessed by investigator | Approximately 4 years | 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 | Approximately 4 years | 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) | Approximately 4 years | 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 | Through 90 days after the last study intervention; Approximately 4 years | 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. |
| Phase 2: Serum concentrations of PF-08634404 | Approximately 21 months | Predose and postdose concentrations of PF-08634404 |
| Phase 2: Incidence of Anti-Drug Antibody (ADA) against PF-08634404 | Approximately 21 months | — |
| Phase 3: ORR using RECIST 1.1 as assessed by BICR | Approximately 4 years | ORR by BICR is defined as the proportion of participants with a Best Overall Response (BOR) of confirmed CR or confirmed PR per RECIST 1.1 as assessed by BICR. |
| Phase 3: ORR using RECIST 1.1 as assessed by investigator | Approximately 4 years | ORR by investigator is defined as the proportion of participants with a BOR of confirmed CR or confirmed PR per RECIST 1.1 as assessed by investigator. |
| Phase 3: Progression free survival (PFS) using RECIST 1.1 as assessed by investigator | Approximately 4 years | PFS by investigator 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 investigator, or death due to any cause, whichever occurs first |
| Phase 3: DOR using RECIST 1.1 as assessed by BICR | Approximately 4 years | DOR 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 BICR, respectively, or death due to any cause, whichever occurs first. |
| Phase 3: DOR using RECIST 1.1 as assessed by investigator | Approximately 4 years | DOR 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 3: PFS2 (PFS after next-line therapy) by investigator | Approximately 4 years | PFS2 is defined as the time from the date of randomization to the date of second objective disease progression or death due to any cause, whichever occurs first |
| Phase 3: Number of participants with treatment-emergent adverse events | Through 90 days after the last study intervention; Approximately 4 years | AEs as characterized by type, frequency, intensity as graded by NCI CTCAE version 5.0, timing, seriousness, and relationship to study intervention(s) |
| Phase 3: Number of participants with laboratory abnormalities | Through 90 days after the last study intervention; Approximately 4 years | 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. |
| Phase 3: Serum concentrations of PF-08634404 | Approximately 21 months | Predose and postdose concentrations of PF-08634404 |
| Phase 3: Incidence of ADA against PF-08634404 | Approximately 21 months | — |
| Phase 3: Change from baseline in Functional Assessment of Cancer Therapy - Gastric (FACT-Ga) Total score | Approximately 4 years | — |
| Phase 3: Time to definitive deterioration in FACT-Ga Total score | Approximately 4 years | — |
| Phase 3: Time to definitive deterioration in Gastric Cancer Subscale (GaCS) score | Approximately 4 years | — |
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed