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Study of zanidatamab with drug combination for patients with HER2 and PD-L1 positive advanced gastroesophageal cancer

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What is this trial about?

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

This study involves patients with Gastroesophageal Adenocarcinoma, which is a type of cancer that develops in the area where the esophagus (the tube connecting the throat to the stomach) meets the stomach. Specifically, this study focuses on a form of this cancer that has spread to other parts of the body, is positive for a protein called HER2, and is also positive for a marker called PD-L1. The treatment being studied includes a combination of several medications: JZP598 (also known as zanidatamab), pembrolizumab, and chemotherapy drugs including oxaliplatin, fluorouracil, and folic acid. All of these medications are given through infusion directly into a vein.

The purpose of this study is to evaluate how well the combination of zanidatamab with pembrolizumab and chemotherapy works in treating patients who have not previously received treatment for their advanced cancer. The study will look at whether this treatment combination can help control the disease and how long patients remain without their cancer getting worse.

During the study, patients will receive the study medications according to a specific treatment schedule that may continue for up to 104 weeks. Throughout this time, doctors will regularly monitor the patients through various examinations and tests to assess how the cancer responds to treatment and to watch for any side effects. The study will measure several outcomes including how many patients respond to the treatment, how long the treatment keeps the cancer under control, and the overall survival of patients. Safety will be carefully monitored by tracking any unwanted effects that occur during treatment, and quality of life will be assessed using questionnaires.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Initial treatment preparation and baseline assessments

    Before starting treatment, certain tests will be performed to ensure your body is ready for the study medications. These include blood tests to check your liver function, kidney function, and blood cell counts.

    A pregnancy test will be performed if applicable, and must be negative within 7 days before starting treatment.

    Your tumor tissue will be tested to confirm the presence of specific markers called HER2 (a protein found on some cancer cells) and PD-L1 (another protein that affects how your immune system responds to cancer).

    Your disease will be assessed using imaging scans to establish a baseline for measuring how the treatment works.

  2. Step 2

    Treatment phase with combination therapy

    You will receive a combination of five medications, all given through intravenous infusion (through a vein in your arm).

    The medications are: zanidatamab (also called JZP598), pembrolizumab, oxaliplatin, folic acid, and fluorouracil.

    All medications will be administered as solutions for infusion at the treatment facility.

    The treatment will be given in cycles. The exact schedule, dosage, and duration of each medication will be determined by the study doctor based on the study protocol.

    Treatment will continue until your disease progresses, unacceptable side effects occur, or other reasons determined by your doctor.

  3. Step 3

    Regular monitoring and assessments during treatment

    Throughout the treatment period, you will have scheduled visits to the treatment facility.

    Regular blood tests will be performed to monitor your liver function, kidney function, blood cell counts, and blood clotting ability.

    Imaging scans will be performed periodically to assess how your cancer is responding to treatment.

    Your doctor will monitor you for any side effects or adverse events. The severity and frequency of any side effects will be recorded.

    You will be asked to complete quality of life questionnaires to assess how you are feeling during treatment.

  4. Step 4

    Response evaluation

    Your response to treatment will be evaluated using imaging scans and physical examinations.

    The study will assess whether your cancer has shrunk (partial response), disappeared completely (complete response), stayed the same (stable disease), or grown (disease progression).

    These assessments will continue throughout your participation in the treatment phase.

  5. Step 5

    End of treatment

    Treatment will end when your disease progresses, side effects become too severe, or for other medical reasons determined by your doctor.

    A final assessment will be performed when you stop receiving the study medications.

  6. Step 6

    Follow-up period

    After stopping treatment, you will enter a follow-up period where your health status will continue to be monitored.

    You will have scheduled follow-up visits where your doctor will check on your overall health and survival status.

    Quality of life questionnaires may continue to be administered during this period.

    If applicable, contraception must be continued for 4 months after the last dose of zanidatamab or pembrolizumab, or 6 months after the last dose of chemotherapy, whichever occurs last.

Who can join the trial?

19 criteria

  • You must sign and date a written consent form before any study procedures begin
  • You must be at least 18 years old
  • You must have been diagnosed with gastroesophageal adenocarcinoma, which is a type of cancer affecting the stomach or the tube connecting your mouth to your stomach, that cannot be removed by surgery and has spread to other parts of your body
  • Your cancer must be HER2-positive, which means your cancer cells have high levels of a specific protein called HER2 that helps cancer cells grow
  • Your cancer must be PD-L1-positive, which means your cancer cells have a certain marker that can be measured by a test
  • You must have cancer that can be seen and measured on imaging scans
  • You must not have received any previous treatment for your cancer after it has spread, although prior treatment given before or after surgery is allowed if it ended at least 6 months before joining this study
  • You must not have received previous anti-HER2 treatment, which are medicines that specifically target the HER2 protein
  • You must have a performance status of 0 or 1, which means you are able to care for yourself and perform light activities
  • Your liver must be working adequately, shown by blood tests measuring enzymes and bilirubin, which is a substance produced when your body breaks down red blood cells
  • Your kidneys must be working adequately, shown by blood tests measuring creatinine, which is a waste product filtered by your kidneys
  • Your blood must have enough cells, including neutrophils which are white blood cells that fight infection, and platelets which help your blood clot
  • Your blood must clot normally, shown by blood tests measuring clotting time
  • If you are a woman who can become pregnant, you must have a negative pregnancy test within 7 days before starting the study treatment
  • If you are a woman who can become pregnant, you must not be breastfeeding
  • If you are a woman who can become pregnant, you must use highly effective birth control during treatment and for up to 6 months after your last dose of study medicine
  • If you are a man who is sexually active with women who can become pregnant, you must use birth control during treatment and for up to 6 months after your last dose of study medicine
  • If you are a man, you must agree not to donate sperm during treatment and for up to 6 months after your last dose of study medicine
  • You must be willing and able to attend all scheduled visits, follow the treatment plan, and complete all required tests

Who cannot join the trial?

1 criterion

  • The study does not list specific reasons why patients cannot participate in this clinical trial in the provided information.
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Investigated drugs

  • Zanidatamab

    is a targeted therapy that works against a protein called HER2, which is found on the surface of some cancer cells. This medication is designed to attach to HER2 and help stop the cancer cells from growing and dividing.

  • Pembrolizumab

    is an immunotherapy medication that helps your immune system fight cancer. It works by blocking a protein called PD-1, which allows your body's natural defenses to recognize and attack cancer cells more effectively.

  • Chemotherapy

    refers to medications that kill cancer cells or stop them from growing. In this trial, chemotherapy will be used along with the other medications to treat the cancer.

What is already known about the treatment

  • Zanidatamab

    Zanidatamab is an experimental medication given through an intravenous infusion (directly into a vein) that is currently being studied in clinical trials for the treatment of gastroesophageal adenocarcinoma, a type of cancer affecting the stomach and esophagus. This drug belongs to a class of medications called bispecific antibodies, which means it works by attaching to two different parts of the HER2 protein found on cancer cells, blocking signals that help the cancer grow and marking these cells for destruction by the immune system. In this trial, zanidatamab is being tested in combination with pembrolizumab (an immunotherapy drug) and chemotherapy to see if this combination can effectively treat patients whose tumors have high levels of HER2 and PD-L1 proteins.

  • Pembrolizumab

    Pembrolizumab is an approved cancer medication administered through intravenous infusion that is widely used in medical practice for treating various types of cancers, including gastroesophageal adenocarcinoma. This drug belongs to a class called immune checkpoint inhibitors and works by blocking a protein called PD-1 on immune cells, which prevents cancer cells from hiding from the body's immune system and allows the immune system to recognize and attack the cancer more effectively. In this clinical trial, pembrolizumab is being combined with zanidatamab and chemotherapy to enhance the overall treatment effect in patients with tumors that show positive markers for both HER2 and PD-L1 proteins.

Investigated diseases

Gastroesophageal Adenocarcinoma – This is a type of cancer that develops in the glandular cells where the esophagus meets the stomach or in the upper part of the stomach. The disease begins when abnormal cells in these areas start to grow and multiply uncontrollably, forming a tumor. Over time, the cancer can spread through the layers of the organ wall and may extend to nearby tissues and lymph nodes. In advanced stages, the cancer cells can travel through the bloodstream or lymphatic system to distant parts of the body, a process called metastasis. Patients with this condition often experience difficulty swallowing, weight loss, and digestive discomfort as the disease progresses. The cancer may be associated with certain risk factors including chronic acid reflux, obesity, and smoking.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IITrial ID2025-522718-22-00Protocol codeIKF/AIO-ZANGEAEstimated enrolment80 patientsSponsorInstitut fuer Klinische Krebsforschung IKF GmbH

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