NCT07176312

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

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

Interventions

Type	Name	Description
DRUG	Zanidatamab	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)
DRUG	Pembrolizumab	Pembrolizumab 400 mg, administered i.v. on day 1 of every third cycle (Q6W)
DRUG	mFOLFOX	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)

Timeline

• Start date: 2026-01-16
• Primary completion: 2029-03-01
• Completion: 2029-03-01
• First posted: 2025-09-16
• Last updated: 2026-02-04

Locations

20 sites across 1 country: Germany