Perioperative Zanidatamab and Chemotherapy for HER2 Positive Gastroesophageal Cancer

Phase 2Not Yet RecruitingNCT07477444

Universitaire Ziekenhuizen KU Leuven29 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Gastroesophageal Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Incidence of Qualifying Safety Events (Phase 1b Safety Run-in)

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.

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)

Pathological Complete Response (pCR) Rate (Total Population)

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.

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)