Zimberelimab + Domvanalimab in Gastroesophageal Adenocarcinoma

NCT07283848 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 25-569
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to understand whether study drugs domvanalimab and zimberelimab are safe and effective in combination with standard chemotherapy for patients with operable cancer of the esophagus, stomach, or gastroesophageal junction (where the stomach meets the esophagus). All participants will receive the study treatment. Participants will receive chemotherapy and two immune therapies drugs (domvanalimab and zimberelimab) for up to 4 months before surgery. After surgery and at least a 4 week recovery, participants will receive domvanalimab and zimberelimab for up to 8 months. After completion of the study treatment, participants will be followed for up to 5 years per standard of care.

Conditions

Adenocarcinoma Stomach; Adenocarcinoma Gastroesophageal Junction

Keywords

stomach cancer; immunotherapy; gastroesophageal junction cancer; checkpoint inhibitor; stomach adenocarcinoma; gastric adenocarcinoma; gastric cancer

Outcome Measures

Primary Outcomes (1)

• Rate of Event-free Survival (EFS)

  The primary endpoint is the rate of 24-month EFS. EFS is defined as the time from enrollment to the first of the following events: radiographic disease progression per RECIST 1.1; local or distant recurrence as assessed by computer tomography (CT) scan or biopsy if indicated (for participants who are disease free after surgery); clinical progression as evidenced by peritoneal carcinomatosis confirmed by preoperative laparoscopy or laparotomy (for participants who are confirmed to be free of peritoneal involvement by laparoscopy at screening); or death due to any cause. A second primary malignancy, or radiographic progressive disease (PD) during the neoadjuvant phase that does not preclude successful surgery (i.e., disease free after surgery), are not considered EFS events.

  From enrollment to up to 24 months after enrollment

Secondary Outcomes (5)

• Rate of major pathologic response (MPR)

  From enrollment to surgery, up to 24 weeks

• Rate of pathological complete response (pCR)

  From enrollment to surgery, up to 24 weeks

• Disease-free survival (DFS)

  From surgery through up to 24 months post surgery

• Overall survival (OS)

  From enrollment through up to 5 years post surgery (up to 5.5 years total)

• Incidence and Severity of Adverse Events

  Day 1 of treatment through 100 days post end of treatment (up to 548 days)

Study Arms (1)

Zimberelimab + Domvanalimab +neoadjuvant FLOT

EXPERIMENTAL

Patients will receive up to 8 2-week cycles of domvanalimab, zimberelimab and FLOT (fluorouracil (5-FU), oxaliplatin, leucovorin, and docetaxel) via intravenous infusion (IV). If there is no evidence of progressive disease and patients remain good surgical candidates, they will undergo curative intent surgical resection as per standard of care. Beginning 4-12 weeks after surgery, patients will receive domvanalimab + zimberelimab via IV for up to 8 28-day cycles. Participants will be followed for up to 5 years.

Drug: Zimberelimab; Drug: Domvanalimab; Drug: FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)

Interventions

Zimberelimab DRUG

480mg administered intravenously once every 4 weeks before surgery (up to 4 doses) and once every 4 weeks after surgery (up to 8 doses).

Also known as: AB122

Zimberelimab + Domvanalimab +neoadjuvant FLOT

Domvanalimab DRUG

1600mg administered by intravenous \[IV\] infusion over about 60 minutes once every 4 weeks before surgery (up to 4 doses), and once every 4 weeks after surgery (up to 8 doses).

Also known as: AB154

Zimberelimab + Domvanalimab +neoadjuvant FLOT

FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel) DRUG

Administered by IV every 2 weeks before surgery for up to 8 doses. FLOT is given using a continuous IV infusion over 24 hours. FLOT will be administered according to standard clinical practice. Participants will receive FLOT before surgery but not after surgery.

Zimberelimab + Domvanalimab +neoadjuvant FLOT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically proven adenocarcinoma of the stomach or gastroesophageal junction (GEJ), including Siewert I-III adenocarcinomas of the GEJ
• Tumors must have a programmed death ligand-1 (PDL1) expression score of at least 1 or greater (≥1) by any testing method (any conventional immunohistochemistry assay and any calculation)
• Participants must be treatment naïve.
• Age ≥18 years.
• ECOG performance status ≤1
• Participants must have adequate organ and marrow function as defined below:
• leukocytes ≥2,000/mcL
• absolute neutrophil count ≥1,500/mcL
• hemoglobin \> 9 g/dL
• platelets ≥100,000/mcL
• total bilirubin ≤ 1.5x institutional upper limit of normal (ULN) unless documented Gilbert's disease
• AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
• Creatinine clearance ≥50 mL/min.
• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

You may not qualify if:

• Prior anti-PD-1/PD-L1/TIGIT treatment
• Participants who are receiving any other investigational agents or other anticancer therapies.
• Patients with brain metastases are excluded. Brain metastases constitute stage IVB disease and are not approached with curative intent and are therefore excluded.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to domvanalimab or zimberelimab
• Subjects with any condition requiring systemic treatment with either corticosteroids (\>2mg daily dexamethasone equivalent) or other immunosuppressive medications within 14 days of treatment. Premedication for hypersensitivity reactions (e.g. to contrast for CT or gadolinium for MRI) is allowed.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), idiopathic pneumonitis, or clinical evidence of active pneumonitis. History of radiation pneumonitis/fibrosis in the radiation field is permitted.
• Participants with uncontrolled intercurrent illness that would interfere with ability to participate in the opinion of the treating investigator.
• Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and/or nursing women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with domvanalimab or zimberelimab.
• Patients with a history of another primary malignancy that is currently clinically significant and has potential for metastases or currently requires active intervention (except for hormonal therapy for breast or prostate cancer).
• New York Heart Association \[NYHA\] Class III or IV (see Appendix D, New York Heart Association \[NYHA\] Classification) within the previous 2 months; if \>2 months, cardiac function must be within normal limits and the patient must be free of cardiac-related symptoms.
• HIV Infection: Participants with a known history of Human Immunodeficiency Virus (HIV) infection are excluded unless they meet all of the following criteria:
• Stable antiretroviral therapy (ART) for at least 12 weeks prior to enrollment.
• No history of AIDS-defining conditions.
• CD4+ T-cell count ≥ 350 cells/mm³ at screening.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Arcus Biosciences, Inc.: collaborator
• Gateway for Cancer Research: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

zimberelimab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Officials

• Samuel J. Klempner, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 6, 2025
• First Posted: December 16, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2029
• Last Updated: December 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)