Perioperative Zanidatamab and Chemotherapy for HER2 Positive Gastroesophageal Cancer

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.

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Key information

Conditions

GastroEsophageal Cancer

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Zanidatamab Combined with Chemotherapy

Drug

This intervention combines perioperative zanidatamab with chemotherapy and the PD-1 inhibitor tislelizumab for HER2-positive gastroesophageal adenocarcinoma

Primary outcomes

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.
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.

Sponsors and collaborators

Lead sponsor

Universitaire Ziekenhuizen KU Leuven

Other

Registry information

Official study title

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

Acronym: HER-OIC

Important dates

Study start: 2026
Primary completion: 2028
Study completion: 2033
First posted: Mar 17, 2026
Registry last updated: Mar 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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