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Adenocarcinoma StomachPhase 2NCT07283848

Zimberelimab + Domvanalimab in Gastroesophageal Adenocarcinoma

A Phase 2 study testing Zimberelimab, Domvanalimab and FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel) in people with Adenocarcinoma Stomach and Adenocarcinoma Gastroesophageal Junction, run by Massachusetts General Hospital at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Zimberelimab, Domvanalimab and FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
1 Feb 2026to 1 Dec 2029
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.
  • Patients must have been deemed to have resectable disease by the medical oncology provider after reviewing with the multidisciplinary team including surgery. This must be documented in the medical record by the medical oncologist.
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation including six months after last study dose.
  • Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of domvanalimab and/or zimberelimab administration. Males who have had a successful vasectomy (confirmed azoospermia, documentation needed) require no additional contraception.
  • Ability to understand and the willingness to sign a written informed consent document.
  • The participant is a non-smoker or light smoker who smokes no more than 10 cigarettes, 2 cigars, 2 pipes, or other nicotine equivalents (eg, vape, snuff, gum) of tobacco per day; willing to limit smoking during the treatment period to 4 cigarettes or 1 cigar per day.

Who cannot join

  • 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.
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  • 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.
  • HIV viral load ≤ 50 copies/mL at screening.
  • No significant comorbidities associated with HIV infection that could interfere with the safety or efficacy of the investigational treatment.
  • No concurrent use of prohibited medications that may interfere with the study drug or cancer therapy.
  • Fredericia's corrected QT interval (QTcF) ≥ 450 ms for men and ≥ 470 ms for women on ECG conducted during screening.
  • Active systemic infection requiring intravenous antibiotics or intravenous monoclonal antibody treatments within 7 days of cycle 1 day 1.
  • Use of any live vaccines against infectious diseases within 28 days of first dose of study drug.
  • History of trauma or major surgery within 28 days prior to the first dose of study drug (placement of central venous access catheter [eg, port or similar] is not considered a major surgical procedure).
  • Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or resolved childhood asthma/atopy. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
  • Any history of clinically significant pulmonary embolism within 30 days causing clinical symptoms including but not limited to shortness of breath, pleuritic chest pain, dyspnea on exertion and/or evidence of unresolved right heart strain on EKG or echocardiography.
  • History of allogeneic stem cell or solid organ transplantation

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

Other trials in United States

About this study

Official title: A Single-Arm, Phase II Study of Perioperative Zimberelimab + Domvanalimab and Neoadjuvant Chemotherapy in Locally Advanced, Resectable, Gastroesophageal Adenocarcinoma

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.

Read the detailed description

This is a single-center, phase II study evaluating the efficacy, activity and safety of domvanalimab and zimberelimab with standard chemotherapy (FLOT: fluorouracil (also called 5FU), oxaliplatin, leucovorin, docetaxel) in locally advanced, resectable, gastroesophageal adenocarcinomas. This study will enroll up to 28 participants with untreated, locally advanced, resectable adenocarcinoma of the stomach and gastroesophageal junction. Participants will receive up to 8 2-week cycles of domvanalimab , zimberelimab, and FLOT. If there is no evidence of progressive disease and participants remain good surgical candidates, they will undergo surgery 4-6 weeks after last dose of FLOT as per standard of care. Beginning 4-12 weeks after surgery, participants will receive domvanalimab + zimberelimab for up to 8 4-week cycles. Total treatment duration is approximately 12 months. Participants will remain on study unless they do not safely tolerate therapy, develop progressive disease, or withdraw consent. Participants will be followed for up to 5 years.

The U.S. Food and Drug Administration (FDA) has not approved zimberelimab, domvanalimab, and FLOT in combination as a treatment for any disease. The FDA has not approved zimberelimab as a treatment for any disease. The FDA has not approved domvanalimab as a treatment for any disease. The FDA has approved FLOT (5-FU, oxaliplatin, leucovorin, and docetaxel) as approved chemotherapy drugs used to treat stomach and gastroesophageal cancers, as well as among many other cancers. Arcus Biosciences, Inc. (with Gilead Sciences) are providing study drugs zimberelimab and domvanalimab. Gateway for Cancer Research, a nonprofit organization, is providing funding for this study.

Being tested
Zimberelimab, Domvanalimab, FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)
Keywords
stomach cancer, immunotherapy, gastroesophageal junction cancer, checkpoint inhibitor, stomach adenocarcinoma, gastric adenocarcinoma, gastric cancer
Medical subject headings
Stomach Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZimberelimabDrug

    Also called AB122

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

  • DomvanalimabDrug

    Also called AB154

    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).

  • 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.

Study groups in NCT07283848
Study groupRoleWhat they receive
Zimberelimab + Domvanalimab +neoadjuvant FLOTExperimentalPatients 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.
Receives: Drug: Zimberelimab; Drug: Domvanalimab; Drug: FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: From enrollment to up to 24 months after enrollment

Secondary outcomes (5)

  1. Rate of major pathologic response (MPR)

    MPR Rate is the sum of the proportions of treated participants having either a pathologic complete response (TRG1a, equivalent to pathological complete regression; no residual tumour cells) or subtotal regression with <10% residual tumor cells (TRG1b). Tumor regression grade will be quantified using the Becker regression criteria. Pathological staging will be assessed according to the 7th edition of the TNM International Union Against Cancer (UICC) classification.

    Measured: From enrollment to surgery, up to 24 weeks

  2. Rate of pathological complete response (pCR)

    Pathologic complete response (pCR) rate is defined as the proportion of treated participants having complete pathologic response, defined as no invasive disease within an entirely submitted and evaluated gross lesion, and histologically negative nodes. Pathological staging will be according to the 7th edition of the TNM International Union Against Cancer (UICC) classification.

    Measured: From enrollment to surgery, up to 24 weeks

  3. Disease-free survival (DFS)

    DFS is assessed per RECIST 1.1 and defined as the time from surgical resection to the earlier of documented disease recurrence or death due to any cause. The follow-up of patients who neither recur nor die will be censored at the date of last follow-up. The distributions of DFS will be summarized using the method of Kaplan-Meier. 12 and 24 month DFS will be calculated.

    Measured: From surgery through up to 24 months post surgery

  4. Overall survival (OS)

    Overall Survival (OS) is defined as the time from registration to death due to any cause or censored at date last known alive. 2 and 5 year overall survival distributions will be summarized using the method of Kaplan-Meier.

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

  5. Incidence and Severity of Adverse Events

    Adverse events will be graded according to the NCI CTCAE, version 5.0. The incidence of adverse events will be evaluated for all patients combined. Adverse events, both in terms of MedDRA preferred terms and CTCAE (V5) will be listed individually. The number of patients experiencing new or worsening of each type of adverse event will be summarized according to the worst grade observed; incidence rates of adverse events and grade 3-5 adverse events will be summarized with 90% exact binomial confidence intervals.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Dec 2025
  2. Study start1 Feb 2026 (estimated)
  3. Primary completion1 Dec 2026 (estimated)
  4. Study completion1 Dec 2029 (estimated)

Why it stopped: The pharmaceutical company is not moving forward with this intervention due to lack of efficacy.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07283848
Sponsor's protocol ID
25-569
Status last verified
Dec 2025
First submitted
6 Dec 2025
Last updated
26 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: Samuel J. Klempner, MD, sklempner@mgb.org. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zimberelimab, Domvanalimab and FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel) in people with Adenocarcinoma Stomach and Adenocarcinoma Gastroesophageal Junction, run by Massachusetts General Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 26 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of Event-free Survival (EFS) (time frame: From enrollment to up to 24 months after enrollment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07283848.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Dec 2025.

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