A Study of Zanidatamab in Combination With Chemotherapy Plus or Minus Tislelizumab in Patients With HER2-positive Advanced or Metastatic Gastric and Esophageal Cancers

Phase 3

Active, not recruiting

• Conditions: Gastroesophageal Adenocarcinoma (GEA)

• Registration Number: 2023-510319-20-00
• Lead Sponsor: Jazz Pharmaceuticals Ireland Limited

Brief Summary

To compare the efficacy of zanidatamab in combination with chemotherapy or in combination with chemotherapy and tislelizumab to the efficacy of trastuzumab in combination with chemotherapy in subjects with unresectable locally advanced, recurrent or metastatic HER2 positive GEA

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-10-07
• Last Update Posted: 2025-06-06

Recruitment & Eligibility

• Status: Ongoing, recruitment ended
• Sex: Not specified
• Target Recruitment: 251

Inclusion Criteria

1.Histologically confirmed unresectable locally advanced, recurrent or metastatic HER2-positive gastroesophageal adenocarcinoma (adenocarcinomas of the stomach or esophagus, including the gastroesophageal junction), defined as 3+ HER2 expression by IHC or 2+ HER2 expression by IHC with ISHpositivity per central assessment. Subjects with esophageal adenocarcinoma must not be eligible for combined chemoradiotherapy at the time of enrollment. 2.Assessable (measurable or non-measurable) disease as defined by RECIST 1.1. 3.Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, assessed within 3 days prior to randomization 4.Adequate organ function 5.Left ventricular ejection fraction (LVEF) ≥ 50% as determined by either echocardiogram or multiple gated acquisition scan (MUGA)

Exclusion Criteria

1.Prior treatment with a HER2-targeted agent, with the exception of subjects who received HER2-targeted treatment for breast cancer > 5 years prior to initial diagnosis of GEA. 2.Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. 3. Prior treatment with systemic antineoplastic therapy or intraperitoneal chemotherapy for unrespectable locally advanced, recurrent or metastatic GEA. 4.Untreated central nervous system (CNS) metastases, symptomatic CNS metastases, or radiation treatment for CNS metastases within 4 weeks prior to randomization. Stable, treated brain metastases are allowed (defined as subjects who are completely off steroids and anticonvulsantsand are neurologically stable with no evidence of radiographic progression for at least 4 weeks prior to randomization). 5.Known history of or ongoing leptomeningeal disease (LMD). 6.Known additional malignancy that is not considered cured or that has required treatment within the past 3 years. 7.Known active hepatitis 8.Any history of human immunodeficiency virus (HIV) infection 9.Known SARS-CoV-2 infection; subjects with prior infection that has resolved per local institutions' requirements and screening guidance are eligible 10.Clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension or any history of symptomatic congestive heart failure (CHF). 11.QTc Fridericia (QTcF) > 470 ms.

Study & Design

• Study Type: Not specified
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
●Progression-free survival (PFS) by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), assessed by blinded independent central review (BICR)		●Progression-free survival (PFS) by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), assessed by blinded independent central review (BICR)
●Overall survival (OS) The primary PFS analysis will be performed once the target event count has been reached for each comparison. This is estimated to occur 7 months after the last subject is randomized. At this time, interim analyses of OS will be performed.		●Overall survival (OS) The primary PFS analysis will be performed once the target event count has been reached for each comparison. This is estimated to occur 7 months after the last subject is randomized. At this time, interim analyses of OS will be performed.

Secondary Outcome Measures

Name	Time	Method
●Confirmed objective response rate (ORR) by RECIST 1.1, assessed by BICR		●Confirmed objective response rate (ORR) by RECIST 1.1, assessed by BICR
●Duration of response (DOR) by RECIST 1.1, assessed by BICR		●Duration of response (DOR) by RECIST 1.1, assessed by BICR
●PFS by RECIST 1.1, per investigator assessment		●PFS by RECIST 1.1, per investigator assessment
●Change from baseline in health economics and outcomes research / patient-reported outcomes (HEOR/PRO) parameters		●Change from baseline in health economics and outcomes research / patient-reported outcomes (HEOR/PRO) parameters
●Serum concentration and PK parameters for zanidatamab		●Serum concentration and PK parameters for zanidatamab
●Serum concentrations for tislelizumab		●Serum concentrations for tislelizumab

Trial Locations

Locations (79)

UZ Leuven; 🇧🇪 Leuven, Belgium

Universitair Ziekenhuis Gent; 🇧🇪 Gent, Belgium

Cliniques Universitaires Saint-Luc; 🇧🇪 Sint-Lambrechts-Woluwe, Belgium

Centre Hospitalier Universitaire De Liege; 🇧🇪 Liege, Belgium

Imelda; 🇧🇪 Bonheiden, Belgium

Wojewodzkie Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M.Kopernika W Lodzi; 🇵🇱 Lodz, Poland

Pratia S.A.; 🇵🇱 Skorzewo, Poland

Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy; 🇵🇱 Warsaw, Poland

North Estonia Medical Centre Foundation; 🇪🇪 Tallinn, Estonia

East Tallinn Central Hospital; 🇪🇪 Tallinn, Estonia

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UZ Leuven

🇧🇪Leuven, Belgium

Filip Van Herpe

Site contact

+3216344218

filip.vanherpe@uzleuven.be