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Gastroesophageal AdenocarcinomaPhase 2ZANGEANCT07176312

Zanidatamab in Combination With Pembrolizumab and Chemotherapy in HER2 and PD-L1 Positive Metastatic Gastroesophageal Adenocarcinoma (GEA) Patients

A Phase 2 study testing Zanidatamab, Pembrolizumab and mFOLFOX in people with Gastroesophageal Adenocarcinoma and First Line Therapy, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 20 sites in Germany.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The ZANGEA trial is a open-label, single arm, multicenter phase II trial assessing the efficacy of zanidatamab in combination with pembrolizumab and chemotherapy in patients with metastatic gastroesophageal adenocarcinoma (GEA). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Zanidatamab, Pembrolizumab and mFOLFOX
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
20 sitesGermany
Study dates
16 Jan 2026to Mar 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Patient* has signed and dated a written informed consent form in accordance with regulatory and institutional guidelines and approved by an institutional Review Board / Independent Ethics Committee. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.
  • Patient is, in the investigator's judgement, willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study.
  • Patient is ≥ 18 years of age at time of signing the written informed consent.
  • Patient has been diagnosed with histologically confirmed unresectable advanced/metastatic HER2-positive (defined as IHC 3+ or IHC 2+ with ISH+) and PD-L1-positive (combined positive score CPS ≥ 1) gastroesophageal adenocarcinoma per local standard assessment of new or archival tumor tissue. Results of local HER2 and PD-L1 assessment will be retrospectively confirmed by central pathological re-assessment.
  • Note: In case of metachronous metastases, particularly in case of prior treatment with PD-(L)1-antibodies, a fresh re-biopsy should be performed for immunohistochemistry testing (local pathology), if feasible.
  • Patient has assessable disease (measurable or non-measurable) per RECIST v1.1.
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  • Patient did not receive previous palliative treatment. Prior adjuvant or neoadjuvant chemotherapy, immunotherapy, radiotherapy and/or chemoradiotherapy (but not anti HER2-targeted treatment) are permitted as long as the last administration of the last regimen (whichever was given last) occurred at least 6 months prior to enrolment.
  • Patient has ECOG performance status ≤ 1.
  • Patient has adequate hepatic, renal and hematologic functions:
  • Absolute number of neutrophils (ANC) ≥ 1.5 x 10^9/L
  • Platelets ≥ 100x10^3/µL
  • Serum creatinine ≤ 1.5 x ULN or creatinine clearance (measured by 24 h urine) ≥ 30 mL/min (i.e., if serum creatinine level is > 1.5 x upper limit of normal (ULN), then a 24-hour urine test must be performed to check the creatinine clearance to be determined.
  • AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN (or ≤ 5.0 x ULN if liver metastases are present)
  • Total Bilirubin ≤ 1.5 x ULN (or < 3.0 x ULN in case of prior liver involvement or Gilbert's Syndrome)
  • Patient has adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy).
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotrophin [hCG]) within 7 days prior to the start of study drug. Women must not be breastfeeding. WOCBP must use a highly effective method(s) of contraception during the treatment period and for 4 months after last dose of zanidatamab and/or pembrolizumab, or 6 months after the last dose of chemotherapy, whichever occurs last. Males who are sexually active with WOCBP must agree to remain abstinent or follow instructions for method(s) of contraception during the treatment and for 4 months after the last dose of zanidatamab and/or pembrolizumab, or 6 months after the last dose of chemotherapy, whichever occurs last. In addition, male subjects must be willing to refrain from sperm donation during this time.
  • There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the study gender-independently.

Who cannot join

  • Patient has any known contraindication including allergy or hypersensitivity to the trial drugs or any constituent of the products as well as a known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies.
  • Patient received prior anti HER2-targeted treatment for GEA.
  • Patient has malignancies other than the disease under study within 5 years prior to inclusion, except for those with a negligible risk of metastasis or death (e.g., expected 5-year OS > 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent).
  • Patient has untreated known CNS metastases. Patient is eligible, if previous CNS metastases are adequately treated and patient has neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for ≥ 2 weeks prior to enrolment, and did not receive corticosteroids, or is on a stable or decreasing dose of < 10 mg daily prednisone (or equivalent) for ≥ 2 weeks prior to inclusion.
  • Patient has abnormal baseline left ventricular ejection fraction (LVEF < 50 %), assessed by echocardiogram, multigated acquisition (MUGA) scan, or cardiac magnetic resonance imaging (MRI) scan.
  • Patient has active, known, or suspected autoimmune disease. Exception: Type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll. For any cases of uncertainty, it is recommended that the medical expert/sponsor be consulted prior to signing informed consent.
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  • Patient has a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of trial drug administration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Patient has persisting toxicity related to prior therapy (NCI CTCAE v.5.0 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
  • Patient has any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the risk associated with trial participation, trial drug administration, or would impair the ability of the patient to receive trial drug.
  • Patient has significant acute or chronic infections including, among others:
  • Any positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • Any positive test result for hepatitis B virus or hepatitis C virus indicating acute or chronic infection.
  • Patient has history of allogeneic tissue / solid organ transplant.
  • Patient has been incarcerated or involuntarily institutionalized by court order or by the authorities [§ 40 Abs. 1 S. 3 Nr. 4 AMG].
  • Patient is unable to consent because he/she does not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].
  • Patient has evidence of any other disease, neurologic or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of any of the trial medications, puts the patient at higher risk for treatment-related complications or may affect the interpretation of trial results.
  • Patient currently participates in any other interventional clinical study within 30 days before the first administration of the investigational product or at any time during the trial, unless it is an observational (non-interventional) study, or during the follow-up period of an interventional study with last dose of investigational product ≥28 days prior to enrolment in this trial.
  • Patient has a known complete absence of dihydropyrimidine dehydrogenase (DPD) activity or use of any medications known to inhibit DPD (including brivudine, sorivudine and analogs) within 4 weeks prior to enrolment.
  • Female patients, who are pregnant or breast feeding or planning to become pregnant within and 6 months after the end of treatment. Female patients of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of trial treatment.

Trial locations and contacts

20 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Alexander Stein, Prof. Dr. contact

+49 (0) 40 36035220

stein@hope-hamburg.de

Clara Dreyling, Dr. contact

+49 (0)69 5899 787 31

dreyling.clara@ikf-khnw.de

20 sites in 1 country

Germany20 sites, 20 recruiting

  • Charité CVK

    Berlin

    Annika Kurreck, PD Dr.

    Recruiting

  • Vivantes Klinikum im Friedrichshain

    Berlin

    Recruiting

  • Klinikum Bielefeld

    Bielefeld

    Kai Wegehenkel, Dr.

    Recruiting

  • Städtisches Klinikum Dresden

    Dresden

    Harald Schmalenberg, Dr.

    Not yet recruiting

  • Evang. Kliniken Essen Mitte

    Essen

    Christian Müller, Dr.

    Recruiting

  • Krankenhaus Nordwest

    Frankfurt

    Thorsten Götze, Prof. Dr.

    Recruiting

  • Universitätsklinikum Göttingen

    Göttingen

    Ute König, Dr.

    Not yet recruiting

  • Hämatologisch Onkologische Praxis Eppendorf (HOPE)

    Hamburg, 20249

    Alexander Stein, Prof. Dr., +4940360352222, info@hope-hamburg.de

    Recruiting

  • Asklepios Klinik Altona

    Hamburg

    Dirk Arnold, Prof. Dr.

    Recruiting

  • Universitätsklinikum Hamburg Eppendorf

    Hamburg

    Joseph Tintelnot, Dr.

    Recruiting

  • St. Anna Hospital Herne

    Herne

    Viktor Rempel, Dr.

    Recruiting

  • Universitätsklinikum Jena

    Jena

    Udo Lindig, Dr.

    Recruiting

  • Universitätsmedizin Mainz

    Mainz

    Markus Möhler, Prof. Dr.

    Not yet recruiting

  • Johannes Wesling Klinikum Minden

    Minden

    Kai Wille, Dr.

    Not yet recruiting

  • Klinikum rechts der Isar der TU München

    München

    Recruiting

  • LMU Klinikum München Großhadern

    München

    Kathrin Heinrich, Dr.

    Not yet recruiting

  • MVZ für Hämatologie und Onkologie Ravensburg

    Ravensburg

    Recruiting

  • Krankenhaus Barmherzige Brüder Regensburg

    Regensburg

    Recruiting

  • Universitätsklinikum Ulm

    Ulm

    Thomas Ettrich, Dr.

    Recruiting

  • Klinikum Wolfsburg

    Wolfsburg

    Not yet recruiting

Other trials in Germany

About this study

Official title: - ZANGEA - Phase II Study of Zanidatamab in Combination With Pembrolizumab and Chemotherapy in HER2 and PD-L1 Positive Metastatic Gastroesophageal Adenocarcinoma (GEA) Patients

The ZANGEA trial is a open-label, single arm, multicenter phase II trial assessing the efficacy of zanidatamab in combination with pembrolizumab and chemotherapy in patients with metastatic gastroesophageal adenocarcinoma (GEA). The patients need to be previously untreated in the palliative setting and tested positive for HER2 and PD-L1.

Read the detailed description

The ZANGEA trial is designed as a single arm phase II study, which aims to estimate the therapeutic efficacy of the experimental regimen zanidatamab in combination with pembrolizumab and chemotherapy in HER2 and PD-L1 positive metastatic gastroesophageal adenocarcinoma (GEA) without previous palliative treatment.The primary objective is to evaluate the efficacy of this treatment, secondary objectives are to further determine the efficacy, to evaluate safety and tolerability and to assess quality of life (QoL).

In addition, two explorative objectives are defined: preplanned matched-pair analyses comparing the study arm to a historical study arm with trastuzumab, chemotherapy and PD-1 inhibitor (AIO INTEGA) in terms of efficacy, tolerability, and translational data and to correlate analysis between selected molecular tumor, serum and microbiome parameters and clinical data to identify molecular biomarkers predictive for tumor response, toxicity, and survival.

A total of 80 patients will be enrolled in approx. 30 study sites in Germany and Austria.

Being tested
Zanidatamab, Pembrolizumab, mFOLFOX
Keywords
GEA, Gastroesophageal adenocarcinoma, first line therapy, HER2-positive, PD-L1 positive
Medical subject headings
Stomach Neoplasms, Neoplasm Metastasis

What participants receive

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

  • ZanidatamabDrug

    Zanidatamab 1,200 mg (patients <70 kg at baseline) or 1,600 mg (patients ≥70 kg at baseline), administered i.v. on day 1 of each 2-week cycle (Q2W)

  • PembrolizumabDrug

    Pembrolizumab 400 mg, administered i.v. on day 1 of every third cycle (Q6W)

  • mFOLFOXDrug

    modified FOLFOX with Oxaliplatin 85 mg/m2 i.v. on day 1; Folinic Acid 400 mg/m2 i.v. on day 1; 5-FU 2,400 mg/m2 i.v. continuous infusion over 48 hours (no bolus!) on days 1 and 2 of each 2-week cycle (Q2W)

Study groups in NCT07176312
Study groupRoleWhat they receive
Zanidatamab plus pembrolizumab and mFOLFOXExperimentalSingle Arm with Zanidatamab Q2W in combination with pembrolizumab Q6W and mFOLFOX Q2W
Receives: Drug: Zanidatamab; Drug: Pembrolizumab; Drug: mFOLFOX

What is being measured

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

  1. Efficacy of zanidatamab in combination with pembrolizumab and chemotherapy in previously untreated HER2 and PD-L1 positive metastatic gastroesophageal adenocarcinoma (GEA)

    Progression-free survival rate at 12 months (PFS@12), estimated using Kaplan Meier method and defined as proportion of patients alive and progression-free 12 months after start of trial medication

    Measured: 12 months after start of trial medication

Secondary outcomes (3)

  1. To further determine the efficacy of zanidatamab in combination with pembrolizumab and chemotherapy in metastatic GEA.

    Overall response rate (ORR), defined as proportion of patients achieving complete or partial response (CR/PR) acc. to RECIST v1.1.

    Disease control rate (DCR), defined as proportion of patients achieving CR, PR, or stable disease (SD) acc. to RECIST v1.1.

    Duration of response (DoR), defined as time from response initiation (when either CR or PR is first determined) to disease progression acc. to RECIST v1.1 or death due to any cause.

    Progression-free survival (PFS), defined as time from first treatment until date of progression acc. to RECIST v1.1 or death due to any cause.

    Overall survival (OS), defined as time from first treatment until date of death due to any cause.

    Measured: up to 42 months after enrolment

  2. To evaluate safety and tolerability of zanidatamab in combination with pembrolizumab and chemotherapy in metastatic GEA.

    Assessment of safety of the treatment as determined by the incidence, nature, causality, frequency, timing, and severity of adverse events using NCI CTCAE v5.0

    Measured: up to 25 months after first study treatment

  3. Assessment of quality of life (QoL) data

    Assessment of QoL during treatment and follow-up using EORTC QLQ-C30 and EQ-5D-5L questionnaires.

    Measured: up to 42 months after first study treatment

Timeline

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

  1. First posted16 Sep 2025
  2. Study start16 Jan 2026
  3. Primary completionMar 2029 (estimated)
  4. Study completionMar 2029 (estimated)

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
Model description
Prospective, single arm, open-label, multicenter, multinational phase II study. All patients receive zanidatamab in combination with pembrolizumab and mFOLFOX.
Masking
None (open label)
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07176312
Sponsor's protocol ID
IKF/AIO-ZANGEA
Other IDs
2025-522718-22-00, AIO-STO-0425/ass, IKF090, 2025
Acronym
ZANGEA
Status last verified
Jun 2026
First submitted
10 Sep 2025
Last updated
30 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zanidatamab, Pembrolizumab and mFOLFOX in people with Gastroesophageal Adenocarcinoma and First Line Therapy, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 20 sites in Germany.

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 17 inclusion and 19 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: looking for participants now, as of the sponsor's last update on 30 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Germany. 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?

This study is still under way. Results are not available in the source record yet.

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

Contact Alexander Stein, Prof. Dr. (+49 (0) 40 36035220, stein@hope-hamburg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy of zanidatamab in combination with pembrolizumab and chemotherapy in previously untreated HER2 and PD-L1 positive metastatic gastroesophageal adenocarcinoma (GEA) (time frame: 12 months after start of trial medication). 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 NCT07176312.

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 30 Jun 2026.

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