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

NCT07176312 | Recruiting Phase 2 DMC

• 4 other identifiers: IKF/AIO-ZANGEA2025-522718-22-00AIO-STO-0425/assIKF090
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 20

Brief 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.

Conditions

PDL-1; Gastroesophageal Adenocarcinoma; First Line Therapy; HER2 + Gastric Cancer; Metastases

Keywords

GEA; Gastroesophageal adenocarcinoma; first line therapy; HER2-positive; PD-L1 positive

Outcome Measures

Primary Outcomes (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

  12 months after start of trial medication

Secondary Outcomes (3)

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

  up to 42 months after enrolment

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

  up to 25 months after first study treatment

• Assessment of quality of life (QoL) data

  up to 42 months after first study treatment

Other Outcomes (2)

• Preplanned matched-pair analyses comparing the study arm to a historical study arm

  after end of study of all patients, up to 54 months after first patient enrolment

• correlation analysis between selected molecular tumor, serum and microbiome parameters and clinical data to identify molecular biomarkers predictive for tumor response, toxicity, and survival.

  after end of study of all patients, up to 54 months after first patient enrolment

Study Arms (1)

Zanidatamab plus pembrolizumab and mFOLFOX

EXPERIMENTAL

Single Arm with Zanidatamab Q2W in combination with pembrolizumab Q6W and mFOLFOX Q2W

Drug: Zanidatamab; Drug: Pembrolizumab; Drug: mFOLFOX

Interventions

Pembrolizumab DRUG

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

Zanidatamab plus pembrolizumab and mFOLFOX

mFOLFOX DRUG

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)

Zanidatamab plus pembrolizumab and mFOLFOX

Zanidatamab DRUG

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)

Zanidatamab plus pembrolizumab and mFOLFOX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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).

You may not qualify if:

• 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 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:
• 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.

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead
• Jazz Pharmaceuticals: collaborator

Study Sites (20)

Charité CVK

Berlin, Germany

NOT YET RECRUITING

Vivantes Klinikum im Friedrichshain

Berlin, Germany

NOT YET RECRUITING

Klinikum Bielefeld

Bielefeld, Germany

NOT YET RECRUITING

Städtisches Klinikum Dresden

Dresden, Germany

NOT YET RECRUITING

Evang. Kliniken Essen Mitte

Essen, Germany

NOT YET RECRUITING

Krankenhaus Nordwest

Frankfurt, Germany

NOT YET RECRUITING

Universitätsklinikum Göttingen

Göttingen, Germany

NOT YET RECRUITING

Hämatologisch Onkologische Praxis Eppendorf (HOPE)

Hamburg, 20249, Germany

RECRUITING

Asklepios Klinik Altona

Hamburg, Germany

RECRUITING

Universitätsklinikum Hamburg Eppendorf

Hamburg, Germany

RECRUITING

St. Anna Hospital Herne

Herne, Germany

RECRUITING

Universitätsklinikum Jena

Jena, Germany

NOT YET RECRUITING

Universitätsmedizin Mainz

Mainz, Germany

NOT YET RECRUITING

Johannes Wesling Klinikum Minden

Minden, Germany

NOT YET RECRUITING

Klinikum rechts der Isar der TU München

München, Germany

RECRUITING

LMU Klinikum München Großhadern

München, Germany

NOT YET RECRUITING

MVZ für Hämatologie und Onkologie Ravensburg

Ravensburg, Germany

NOT YET RECRUITING

Krankenhaus Barmherzige Brüder Regensburg

Regensburg, Germany

NOT YET RECRUITING

Universitätsklinikum Ulm

Ulm, Germany

RECRUITING

Klinikum Wolfsburg

Wolfsburg, Germany

NOT YET RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms; Neoplasm Metastasis

Interventions

zanidatamab; pembrolizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Salah-Eddin Al-Batran, Prof. Dr.

  Frankfurter Institut für Klinische Krebsforschung IKF GmbH

  STUDY DIRECTOR

• Alexander Stein, Prof. Dr.

  Hämatologisch-Onkologische Praxis Eppendorf University Cancer Center Hamburg

  PRINCIPAL INVESTIGATOR

Central Study 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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, single arm, open-label, multicenter, multinational phase II study. All patients receive zanidatamab in combination with pembrolizumab and mFOLFOX.

Study Record Dates

• First Submitted: September 10, 2025
• First Posted: September 16, 2025
• Study Start: January 16, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (20)