SYMBIOTIC-GI-16: A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Chemotherapy in Previously Untreated Participants With LA/m Gastroesophageal Cancers

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-07-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2025-524717-86-00

ClinicalTrials.gov

NCT07392892

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Safety, Efficacy

Phase 2
- To evaluate antitumor activity of PF-08634404 in combination with chemotherapy.
- To evaluate safety and tolerability of PF-08634404 in combination with chemotherapy.
Phase 3
- To demonstrate that PF-08634404 in combination with chemotherapy (experimental arm) is superior to nivolumab in combination with chemotherapy (control arm) in prolonging PFS by Blinded
Independent Central Review (BICR).
- To demonstrate that PF-08634404 in combination with chemotherapy (experimental arm) is superior to nivolumab in combination with chemotherapy (control arm) in prolonging OS.

Secondary objectives 9

1. Phase 2; To evaluate additional measures of efficacy of PF-08634404 in combination with chemotherapy.
2. Phase 2; To evaluate additional measures of safety and tolerability of PF-08634404 in combination with chemotherapy.
3. Phase 2; To evaluate the pharmacokinetics (PK) of PF- 08634404 in combination with chemotherapy.
4. Phase 2; To evaluate the immunogenicity of PF-08634404 in combination with chemotherapy.
5. Phase 3; To evaluate additional measures of efficacy for the experimental and control arms.
6. Phase 3; To characterize the overall safety profile and tolerability for the experimental and control arms.
7. Phase 3; To evaluate the PK of PF-08634404 in combination with chemotherapy.
8. Phase 3; To evaluate the immunogenicity of PF-08634404 in combination with chemotherapy.
9. Phase 3; To evaluate PROs for the experimental and control arms.

Conditions and MedDRA coding

LOCALLY ADVANCED OR METASTATIC GASTRIC, GASTROESOPHAGEAL JUNCTION, OR ESOPHAGEAL ADENOCARCINOMA

Regulatory references

Plan to share IPD

Yes

IPD plan description

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.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. 18 years of age or older (or the minimum age of consent in accordance with local regulations) at screening.
2. 2. Histologically or cytologically confirmed diagnosis of gastric, gastroesophageal junction, or esophageal adenocarcinoma, with evidence of locally advanced unresectable or metastatic disease.
3. 3. For Phase 2: At least one measurable lesion according to RECIST 1.1 per investigator assessment. Participants with prior definitive radiotherapy must have measurable disease per RECIST 1.1 that is outside the radiation field or have unequivocal progression of previously irradiated lesions. For Phase 3: At least one evaluable lesion according to RECIST 1.1 per investigator.
4. 4. No prior systemic therapy for advanced or metastatic disease.
5. 5. ECOG PS score of 0 or 1.
6. 6. Sufficient tumor tissue available to submit for correlative studies, either as an FFPE tumor tissue block, or slides containing unstained FFPE tumor tissue sections, from a core or excisional biopsy (cytology samples, including cell blocks generated from FNA biopsies, and biopsies containing bone are not adequate).
7. 7. Participants whose tumors express PD-L1 (TAP ≥1% or CPS ≥1) based on local testing results.
8. 8. HER2-negative status based on local testing results.
9. 9. Adequate hematologic, hepatic, and renal function.

Exclusion criteria 18

1. 1. Participants have squamous cell or undifferentiated gastroesophageal cancer.
2. 9. Clinically significant cardiovascular disease, or other comorbidities, within 6 months prior to the first dose.
3. 11. Evidence of non-infectious or drug-induced ILD pneumonitis that: -Was previously diagnosed and was managed with parenteral steroids for any duration or oral steroids for >6 weeks, or; -Had onset during or after treatment with immunotherapy, improved or resolved, then recurred after immunotherapy rechallenge, or; -Is currently diagnosed and managed with systemic therapy, or; -Is suspected on radiologic imaging at screening.
4. 10. Participants with active autoimmune diseases requiring systemic treatment within the past 2 years prior to the first dose of study intervention (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). a) Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic disease modifying treatment and is permitted. b)Participants with vitiligo, psoriasis, type 1 diabetes mellitus or resolved childhood asthma/atopy are allowed. c) Participants with Sjögren’s syndrome are allowed.
5. 2. Participants with known active CNS metastases, including leptomeningeal, brainstem, meningeal or spinal cord metastases or compression are excluded.
6. 3. Known DPD deficiency (refer to the local 5-FU and capecitabine label or local clinical guidance for DPD status recommendation prior to starting treatment).
7. 4. Clinically significant risk of hemorrhage or fistula.
8. 5. Major surgery or severe trauma within 4 weeks prior to the first dose, or planned major surgery during the study; minor local surgery (excluding peripherally inserted central catheter placement and implantable central venous port placement) within 3 days prior to the first dose. Participants must have recovered adequately from the toxicity or complications from the surgery prior to starting study intervention.
9. 6. History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
10. 7. Any Grade ≥3 bleeding/hemorrhage events within 28 days of Cycle 1 Day 1, or prior history of clinically significant bleeding events, including unhealed wounds following surgical procedure.
11. 8. Participants with acute, chronic, or symptomatic infections.
12. 12. Unresolved toxicities from prior antitumor therapy that did not recover to NCI CTCAE version 5.0 Grade 0 or 1 or to levels specified in the inclusion/exclusion criteria, with the exception of alopecia. Participants who experience irreversible toxicity that is not expected to worsen with continued administration of the study intervention (eg, hearing loss) may be enrolled in the study after consultation with the medical monitor. Participants with long-term toxicity from radiotherapy that is deemed irreversible by the investigator may be enrolled in the study after consultation with the medical monitor.
13. 13. Grade >1 baseline peripheral neuropathy.
14. 14. History of esophageal varices, severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding within 6 months prior to the first dose.
15. 15. Participants with any history of another malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death (eg, 5-year OS ≥ 90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer. Participants with a history of other curatively treated malignancies with low risk of recurrence not listed may also be considered eligible after consultation with sponsor or designee.
16. 16. Known or suspected hypersensitivity to any component of study intervention or their excipients at the planned doses.
17. 17. Other circumstances that may increase the study-related risks or interfere with interpretation of the study results, in the opinion of the investigator.
18. 18. Any medical or psychiatric condition including any active suicidal ideation in the past year or suicidal behavior in the past 5 years or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Phase 2; Confirmed objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) as assessed by investigator
2. Phase 2; Adverse events (AEs) as characterized by type, frequency, severity (as graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 5.0), timing, seriousness, and relationship to study intervention
3. Phase 3; PFS using RECIST 1.1 as assessed by BICR
4. Phase 3; OS

Secondary endpoints 9

1. Phase 2; - Duration of response (DOR) using RECIST 1.1 as assessed by investigator - Progression-free survival (PFS) using RECIST 1.1 as assessed by investigator - Overall survival (OS)
2. Phase 2; Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing
3. Phase 2; Predose and postdose concentrations of PF-08634404
4. Phase 2; Incidence of anti-drug antibodies (ADA) against PF-08634404
5. Phase 3; - ORR using RECIST 1.1 as assessed by BICR and by investigator - PFS using RECIST 1.1 as assessed by investigator - DOR using RECIST 1.1 as assessed by BICR and by investigator - PFS2 (PFS after
6. Phase 3; - AEs as characterized by type, frequency, intensity as graded by NCI CTCAE version 5.0, timing, seriousness, and relationship to study intervention(s) - Laboratory test abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0) and timing
7. Phase 3; Predose and postdose concentrations of PF-08634404
8. Phase 3; Incidence of ADA against PF- 08634404
9. Phase 3; - Change from baseline in Functional Assessment of Cancer Therapy – Gastric (FACT-Ga) Total score and Gastric Cancer Subscale (GaCS) score - Time to definitive deterioration in FACT-Ga total score - Time to definitive deterioration in Gastric

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Comparator 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 7

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 19 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications