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Study of Zanidatamab and Tislelizumab Combined with Chemotherapy for Patients with Advanced or Metastatic HER2-positive Gastroesophageal Cancer

Verified siteRegistered drugNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

This study focuses on patients with HER2-positive Gastroesophageal Adenocarcinoma, which is a type of cancer affecting the stomach and esophagus (the tube connecting the mouth to the stomach) that cannot be removed by surgery or has spread to other parts of the body. The study tests a combination of medications including zanidatamab (also known as JZP598), tislelizumab, and standard chemotherapy drugs including capecitabine. These are compared to treatment with trastuzumab (a currently approved therapy) combined with chemotherapy.

The purpose of this research is to determine if using zanidatamab with chemotherapy, either alone or together with tislelizumab, works better than the current standard treatment of trastuzumab with chemotherapy. Zanidatamab and tislelizumab are new medications that work by helping the body's immune system fight cancer cells. During treatment, patients may also receive loperamide, a medication that helps control diarrhea which can occur as a side effect of treatment.

Participants in this study will be randomly assigned to receive either the new treatment combination or the standard treatment. The medications will be given through an intravenous infusion (delivered directly into a vein), while some medications will be taken by mouth. The study treatment may continue for up to 756 days, depending on how well it works and how well it is tolerated by patients.

The research process

The trial runs in 5 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Initial assessment

    Your doctor will perform tests to confirm HER2-positive gastroesophageal cancer that cannot be removed by surgery or has spread to other parts of the body

    A heart test will be done to check if your heart function (LVEF) is at least 50%

    Your overall physical condition will be evaluated using a scale called ECOG, which must show a score of 0 or 1

  2. Step 2

    Assignment to treatment group

    You will be randomly assigned to one of the treatment groups

    Each group receives different combinations of medications through infusion and oral tablets

  3. Step 3

    Treatment administration

    You will receive treatment with one of these combinations:

    - Zanidatamab (given by intravenous infusion) with chemotherapy

    - Zanidatamab with chemotherapy plus tislelizumab (both given by intravenous infusion)

    - Trastuzumab (given by intravenous infusion) with chemotherapy

    Capecitabine will be given as oral tablets as part of the chemotherapy

    Loperamide may be provided as oral medication if needed

  4. Step 4

    Monitoring and evaluation

    Regular scans will be performed to measure how the cancer responds to treatment

    Your health status and any side effects will be monitored throughout the study

    Quality of life questionnaires will need to be completed periodically

    Blood samples will be taken to measure medication levels in your body

  5. Step 5

    Follow-up period

    After completing treatment, you will continue to be monitored to assess long-term results

    The study is expected to continue until June 2027

Who can join the trial?

11 criteria

  • Must have confirmed gastroesophageal adenocarcinoma (cancer of the stomach or esophagus) that is:
    • Cannot be surgically removed (unresectable)
    • Locally advanced
    • Recurrent, or
    • Has spread to other parts of the body (metastatic)
    • Cancer must be HER2-positive, confirmed by specific laboratory tests (IHC 3+ or IHC 2+ with ISH positive)
    • Must have disease that can be measured or assessed by medical imaging
    • Must have good physical functioning ability (ECOG performance status of 0 or 1)
    • Must have adequate organ function
    • Must have good heart function with left ventricular ejection fraction (heart pumping ability) of 50% or higher
    • Can be either male or female
    • Must be an adult (18 years or older)

Who cannot join the trial?

13 criteria

  • Patients with unresectable locally advanced, recurrent or metastatic HER2 negative gastric cancer
  • Previous treatment with zanidatamab or tislelizumab (these are the study medications)
  • History of other cancers within the last 5 years, except for successfully treated non-melanoma skin cancer or cervical cancer in situ
  • Severe heart conditions, including:
    • Uncontrolled high blood pressure
    • Unstable heart disease
    • Heart attack within the past 6 months
    • Active or untreated brain metastases (cancer that has spread to the brain)
    • Serious infections requiring treatment, including active tuberculosis or hepatitis B
    • Known allergic reactions to the study medications or similar drugs
    • Participation in another clinical trial within 30 days before starting this study
    • Pregnancy or breastfeeding
    • Unable to swallow oral medications
    • Any condition that, in the opinion of the study doctor, would make participation unsafe
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Investigated drugs

Zanidatamab is a medication designed to target HER2-positive cancer cells. It works by attaching to HER2 proteins on cancer cells, which helps stop the cancer from growing and spreading. This medication is being studied for treating advanced gastroesophageal cancer. Tislelizumab is an immunotherapy medication that helps the body's immune system fight cancer cells. It works by blocking a protein that normally prevents immune cells from attacking cancer cells, allowing the immune system to better recognize and destroy the cancer. Trastuzumab is an established cancer medication that also targets HER2-positive cancer cells. It has been used for many years to treat various types of HER2-positive cancers by attaching to the HER2 proteins on cancer cells and helping to slow or stop cancer growth. Chemotherapy refers to standard cancer-fighting medications that work by killing rapidly dividing cells throughout the body. These medications are commonly used in combination with targeted therapies to treat cancer.

What is already known about the treatment

  • Zanidatamab

    A novel bispecific antibody administered through intravenous infusion, designed to target HER2-positive cancers, particularly gastroesophageal adenocarcinoma (GEA). This investigational drug works by binding to two different sites on the HER2 receptor, blocking cancer cell growth signals and potentially triggering an immune response against cancer cells. Currently being evaluated in Phase 3 clinical trials, it represents a new approach in targeted cancer therapy when used in combination with standard chemotherapy.

  • Tislelizumab

    An innovative anti-PD-1 antibody delivered via intravenous infusion, developed for cancer immunotherapy. This medication works by blocking the PD-1/PD-L1 pathway, helping to restore the body's immune system ability to detect and fight cancer cells. It is being studied in combination with zanidatamab and chemotherapy for treating HER2-positive gastroesophageal adenocarcinoma, representing a potential advancement in combination immunotherapy approaches.

  • Trastuzumab

    An established monoclonal antibody administered intravenously, specifically targeting HER2-positive cancers. This medication works by attaching to HER2 receptors on cancer cells, blocking growth signals and flagging these cells for destruction by the immune system. It is widely used as a standard treatment for HER2-positive cancers, including gastroesophageal adenocarcinoma, often in combination with chemotherapy.

Investigated diseases

Gastroesophageal Adenocarcinoma (GEA) - A cancer that develops in the cells of the stomach or the junction where the esophagus meets the stomach. The disease begins when healthy cells in the inner lining of these areas become abnormal and grow out of control, forming a tumor. As the cancer progresses, it can grow through the wall of the stomach or esophagus and spread to nearby lymph nodes and other organs. The condition typically develops gradually over time, with cells slowly becoming more abnormal and invasive. GEA can affect the body's ability to digest food properly and may impact nutrient absorption.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2023-510319-20-00Protocol codeZWI-ZW25-301Estimated enrolment919 patientsSponsorJazz Pharmaceuticals Ireland Limited

sourced from the EU Clinical Trials Register and site verification

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