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Zanidatamab in Combination With Pembrolizumab and Chemotherapy in HER2 and PD-L1 Positive Metastatic Gastroesophageal Adenocarcinoma (GEA) Patients | Clinical Trials | Clareo Health

RECRUITINGPHASE2

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

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

NCT07176312•Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

View on ClinicalTrials.gov

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). The patients need to be previously untreated in the palliative setting and tested positive for HER2 and PD-L1.

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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•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.
•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:
•1. Absolute number of neutrophils (ANC) ≥ 1.5 x 10\^9/L
+7 more criteria

Exclusion Criteria

•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.
•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:
+9 more criteria

Locations (20)

Charité CVK

Berlin, Germany

Vivantes Klinikum im Friedrichshain

Berlin, Germany

Klinikum Bielefeld

Bielefeld, Germany

Städtisches Klinikum Dresden

Dresden, Germany

Evang. Kliniken Essen Mitte

Essen, Germany

Krankenhaus Nordwest

Frankfurt, Germany

Universitätsklinikum Göttingen

Göttingen, Germany

Hämatologisch Onkologische Praxis Eppendorf (HOPE)

Hamburg, Germany

Asklepios Klinik Altona

Hamburg, Germany

Universitätsklinikum Hamburg Eppendorf

Hamburg, Germany

Key Dates

Start Date

January 16, 2026

Primary Completion Date

March 1, 2029

Completion Date

March 1, 2029

Last Updated

February 4, 2026

Enrollment

ESTIMATED participants

Conditions

Gastroesophageal AdenocarcinomaFirst Line TherapyHER2 + Gastric CancerPDL-1Metastases

Interventions

Zanidatamab

DRUG

Pembrolizumab

DRUG

mFOLFOX

DRUG

Contacts

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

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: February 4, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

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