Perioperative Zanidatamab and Chemotherapy for HER2 Positive Gastroesophageal Cancer (HER-OIC)

March 18, 2026 updated by: Universitaire Ziekenhuizen KU Leuven

Perioperative Zanidatamab Combined With Chemotherapy in Operable HER2 Positive Locally Advanced Operable Gastroesophageal Adenocarcinoma (GEA): A Phase 1b/2a Single-Arm Trial

The HER-OIC clinical trial is a Phase 1b/2a study investigating a new combination of treatments for patients with HER2-positive gastroesophageal cancer. Standard treatment for localized gastroesophageal cancer usually involves chemotherapy before and after surgery. This study aims to see if adding targeted therapy (zanidatamab) and immunotherapy (tislelizumab) to standard chemotherapy is safe and effectively eliminates the tumor. The goal is to improve the pathological complete response (pCR) rate, which is the percentage of patients who have no visible cancer cells remaining in the tissue removed during surgery.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

29

Phase

  • Phase 2
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Voluntary written informed consent from the participant or their legally authorized representative
  • At least 18 years of age at the time of signing the consent form
  • Agreement to use highly effective birth control methods for both male and female patients
  • WHO-ECOG performance status of 0 or 1
  • Histologically proven HER2-positive gastroesophageal, esophageal, or gastric adenocarcinoma
  • Localized, resectable disease that is fit for perioperative treatment, including surgery
  • Adequate hepatic function
  • Adequate renal function with an estimated Glomerular Filtration Rate (GFR) > 50 mL/min
  • Adequate hematologic function
  • Cardiac ejection fraction

Exclusion Criteria:

  • Prior neoadjuvant or definitive chemoradiation
  • Squamous cell cancer of the esophagus
  • Metastatic or unresectable gastroesophageal cancer
  • Active or relapsing autoimmune diseases, with exceptions for controlled Type 1 diabetes, hypothyroidism (hormone replacement only), controlled celiac disease, or certain skin diseases not requiring systemic treatment
  • Known hypersensitivity to zanidatamab, tislelizumab, or any of their excipients
  • Known Dihydropyrimidine Dehydrogenase (DPD) deficiency
  • Active infections requiring systemic treatment
  • History of significant cardiac disease
  • Previous malignancy within the last 5 years
  • Current participation in another interventional Trial involving an investigational medicinal product or device

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Perioperative Zanidatamab and Chemotherapy
This is a single-arm, open-label trial where participants are assigned to receive specific interventions (zanidatamab, chemotherapy, tislelizumab) based on the study protocol.
Drug: Zanidatamab Combined with Chemotherapy
This intervention combines perioperative zanidatamab with chemotherapy and the PD-1 inhibitor tislelizumab for HER2-positive gastroesophageal adenocarcinoma

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological Complete Response (pCR) Rate (Total Population)
Time Frame: At the time of surgery, which occurs 4 to 12 weeks after the last dose of pre-operative treatment (approximately 12 to 20 weeks after the first dose)
The primary efficacy endpoint is the improvement of the pCR rate, defined as the percentage of patients with no residual invasive cancer in the completely resected tumor specimen and sampled regional lymph nodes. The study aims to detect an improvement from a historical 8% to a 30% pCR rate across the total 29-patient cohort.
At the time of surgery, which occurs 4 to 12 weeks after the last dose of pre-operative treatment (approximately 12 to 20 weeks after the first dose)
Incidence of Qualifying Safety Events (Phase 1b Safety Run-in)
Time Frame: During the neoadjuvant period, which start from the first treatment administration and continues until the end of the fourth preoperative 14-day cycle (8 weeks)
The primary safety endpoint is the incidence of "qualifying safety events," defined as Grade ≥3 diarrhea or any Grade ≥3 treatment-emergent toxicity that results in the inability to administer the planned neoadjuvant chemotherapy or zanidatamab.
During the neoadjuvant period, which start from the first treatment administration and continues until the end of the fourth preoperative 14-day cycle (8 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universitaire Ziekenhuizen KU Leuven

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

June 1, 2028

Study Completion (Estimated)

June 1, 2033

Study Registration Dates

First Submitted

March 12, 2026

First Submitted That Met QC Criteria

March 12, 2026

First Posted (Actual)

March 17, 2026

Study Record Updates

Last Update Posted (Actual)

March 20, 2026

Last Update Submitted That Met QC Criteria

March 18, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • S71017

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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