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A Randomized, Multicenter, Phase 3 Study of Zanidatamab in Combination with Chemotherapy with or without Tislelizumab in Subjects with HER2-positive Unresectable Locally Advanced or Metastatic Gastroesophageal Adenocarcinoma (GEA)

A Study of Zanidatamab in Combination With Chemotherapy Plus or Minus Tislelizumab in Patients With HER2-positive Advanced or Metastatic Gastric and Esophageal Cancers (HERIZON-GEA-01)

Sakanishi Ryuichi

PPD-SNBL K. K.

St Luke's Tover 12F, 8-1 Akashi-cho, Chuo-ku, Tokyo

ryuichi.sakanishi@thermofisher.com

Sakanishi Ryuichi

PPDSNBL K.K.

St Luke's Tover 12F, 8-1 Akashi-cho, Chuo-ku, Tokyo

+81-3-6821-0872

ryuichi.sakanishi@thermofisher.com

Not Recruiting

Aug. 11, 2023

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

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 ISH positivity per central assessment. Subjects with esophageal adenocarcinoma must not be eligible for combined chemoradiotherapy at the time of enrollment.

Assessable (measurable or non-measurable) disease as defined by RECIST 1.1.

Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, assessed within 3 days prior to randomization.

Adequate organ function.

Left ventricular ejection fraction (LVEF) >= 50% as determined by either echocardiogram or multiple gated acquisition scan (MUGA).

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.

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.

Prior treatment with systemic antineoplastic therapy or intraperitoneal chemotherapy for unresectable locally advanced, recurrent or metastatic GEA.

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 anticonvulsants and are neurologically stable with no evidence of radiographic progression for at least 4 weeks prior to randomization).

Known history of or ongoing leptomeningeal disease (LMD).

Known additional malignancy that is not considered cured or that has required treatment within the past 3 years.

Known active hepatitis.

Any history of human immunodeficiency virus (HIV) infection.

Known SARS-CoV-2 infection; subjects with prior infection that has resolved per local institutions' requirements and screening guidance are eligible.

QTc Fridericia (QTcF) > 470 ms.

Clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension or any history of symptomatic congestive heart failure (CHF).

Both

advanced or metastatic GEA, including gastric, GEJ, and esophageal adenocarcinomas.

In this study, subjects will be randomized 1:1:1 into one of three treatment groups: Arm A: Trastuzumab (Herceptin) plus physician's choice of CAPOX or 5-fluorouracil plus cisplatin (FP). Arm B: Zanidatamab plus physician's choice of CAPOX or FP. Arm C: Zanidatamab and tislelizumab plus physician's choice of CAPOX or FP

Investigator decision regarding the chemotherapy regimen (CAPOX or FP) must be determined prior to randomization, and subjects should continue on the selected regimen throughout the duration of chemotherapey. In Japan, only CAPOX chemotherapy is administered in all three treatment arms.

Progression-free survival (PFS) by blinded independent central review (BICR) [ Time Frame: Up to 2.5 years]. The time from randomization to the date of documented disease progression (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) as assessed by BICR or death from any cause.

Overall survival [ Time Frame: Up to 3.5 years]. The time from randomization to death due to any cause.

+81-89-999-1111

June. 21, 2023

No

Argentina/Australia/Belgium/Brazil/Canada/Chile/China/Estonia/France/Georgia/Germany/Greece/Guatemala/India/Ireland/Italy/Republic of Korea/Malaysia/Mexico/Netherlands/Poland/Romania/Serbia/Singapore/South Africa/Spain/Taiwan/Thailand/Turkey/Ukraine