Trial purpose
Cancer treatment
Tumor type
Upper gastrointestinal tract
Age
18+
Trial acronym
HERIZON-GEA-01
Clinical summary
Summary
This is a is a randomised trial with three arms. In the Arm A (Active Comparator), participants will receive Trastuzumab (administered intravenously [IV]) plus the physician's choice of capecitabine plus oxaliplatin (CAPOX) or 5-fluorouracil (5-FU) plus cisplatin (FP). In Arm B (Experimental), participants will receive Zanidatamab (administered via IV) plus physician's choice of CAPOX or FP. In Arm C (Experimental), participants will receive Zanidatamab and tislelizumab (administered via IV) plus physician's choice of CAPOX or FP. For all groups, Capecitabine will be administered orally (PO bid), while oxaliplatin, cisplatin and 5-fluorouracil will be administered via IV. Participants will be tested for HER2 gene-amplification using the ISH-based companion diagnostic assay, and also tested for HER2 protein-expression using the IHC-based companion diagnostic assay.
Conditions
This trial is treating people with HER2-positive stomach and oesophagus cancers
Eligibility
Inclusion
- 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)
Exclusion
- 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)
Inclusion
- You have had treatment, but your cancer has come back (relapsed or recurrent).
- Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
- Your cancer has not spread to other parts of the body (localised).
- You are able to swallow medication by mouth.
Exclusion
- You have certain types of non-cancer medical conditions.
- You have had certain treatments, surgical procedures or drugs.
Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.
More information
Trial Identifiers
Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:
Trial sponsor
Zymeworks Inc
Scientific Title
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)
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