TriangleNCT05152147 · CITED IN SOURCE DOCUMENTS
A Study of Zanidatamab in Combination With Chemotherapy Plus or Minus Tislelizumab in Patients With HER2-positive Advanced or Metastatic Gastric and Esophageal Cancers
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2026-09-01
This study is being done to find out if zanidatamab, when given with chemotherapy plus or minus tislelizumab, is safe and works better than trastuzumab given with chemotherapy. The patients in this study will have advanced human epidermal growth factor 2 (HER2)-positive stomach and esophageal cancers that are no longer treatable with surgery (unresectable) or chemoradiation, and/or have grown or spread to other parts of the body (metastatic).
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
No posted result sections were captured. Registered plans do not establish that a treatment works.
Who could take part
- eligibility Criteria
- Inclusion Criteria: * 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 Criteria: * 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)
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Trastuzumab (Herceptin®) plus physician's choice of capecitabine plus oxaliplatin (CAPOX) or 5-fluorouracil (5-FU) plus cisplatin (FP)
- intervention Names
- Drug: Trastuzumab
- Drug: Capecitabine
- Drug: Oxaliplatin
- Drug: Cisplatin
- Drug: 5-Fluorouracil
- label
- Arm A
- type
- ACTIVE_COMPARATOR
- description
- Zanidatamab plus physician's choice of CAPOX or FP
- intervention Names
- Drug: Zanidatamab
- Drug: Capecitabine
- Drug: Oxaliplatin
- Drug: Cisplatin
- Drug: 5-Fluorouracil
- label
- Arm B
- type
- EXPERIMENTAL
- description
- Zanidatamab and tislelizumab plus physician's choice of CAPOX or FP
- intervention Names
- Drug: Zanidatamab
- Drug: Tislelizumab
- Drug: Capecitabine
- Drug: Oxaliplatin
- Drug: Cisplatin
- Drug: 5-Fluorouracil
- label
- Arm C
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Arm B
- Arm C
- description
- Administered IV
- name
- Zanidatamab
- other Names
- ZW25
- JZP598
- ZIIHERA®
- type
- DRUG
- arm Group Labels
- Arm C
- description
- Administered IV
- name
- Tislelizumab
- type
- DRUG
- arm Group Labels
- Arm A
- description
- Administered intravenously (IV)
- name
- Trastuzumab
- other Names
- Herceptin®
- type
- DRUG
- arm Group Labels
- Arm A
- Arm B
- Arm C
- description
- Administered orally (PO bid)
- name
- Capecitabine
- type
- DRUG
- arm Group Labels
- Arm A
- Arm B
- Arm C
- description
- Administered IV
- name
- Oxaliplatin
- type
- DRUG
- arm Group Labels
- Arm A
- Arm B
- Arm C
- description
- Administered IV
- name
- Cisplatin
- type
- DRUG
- arm Group Labels
- Arm A
- Arm B
- Arm C
- description
- Administered IV
- name
- 5-Fluorouracil
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- intervention Model Description
- multi-cohort, open-label, multicenter study
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 920
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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 blinded independent central review (BICR) or death from any cause
- measure
- Progression-free survival (PFS) by BICR
- time Frame
- Up to 2.5 years
- description
- The time from randomization to death due to any cause
- measure
- Overall survival
- time Frame
- Up to 3.5 years
- secondary Outcomes
- description
- Number of patients who achieved a best overall response of complete response (CR) or (PR) as determined per RECIST 1.1 as assessed by BICR
- measure
- Confirmed objective response rate (ORR) by BICR
- time Frame
- Up to 2.5 years
- description
- The time from the first objective response (CR or PR) per BICR to documented progressive disease per RECIST 1.1 as assessed by BICR or death from any cause
- measure
- Duration of response (DOR) by BICR
- time Frame
- Up to 2.5 years
- description
- The time from randomization to the date of documented disease progression (per RECIST 1.1) as assessed by Investigator or death from any cause
- measure
- PFS per Investigator assessment
- time Frame
- Up to 2.5 years
- description
- Number of patients who achieved a best overall response of CR or PR as determined per RECIST 1.1 as assessed by Investigator
- measure
- Confirmed ORR per Investigator assessment
- time Frame
- Up to 2.5 years
- description
- The time from the first objective response (CR or PR) per Investigator to documented progressive disease per RECIST 1.1 as assessed by Investigator or death from any cause
- measure
- DOR per Investigator assessment
- time Frame
- Up to 2.5 years
- description
- 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 blinded independent central review (BICR) or death from any cause
- measure
- Assessment of Contribution of Components based on Progression-free Survival (PFS) by BICR
- time Frame
- Up to 2.5 years
- description
- The time from randomization to death due to any cause
- measure
- Assessment of Contribution of Components based on Overall Survival
- time Frame
- Up to 3.5 years
- description
- Number of subjects who experienced adverse events or serious adverse events
- measure
- Incidence of adverse events
- time Frame
- Up to 2 years
- description
- Number of patients who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology or chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0
- measure
- Incidence of clinical laboratory abnormalities
- time Frame
- Up to 2 years
- description
- Changes from baseline in the EORTC QLQ-C30 scores
- measure
- Health-related quality of life (HRQoL) as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (core cancer questionnaire) C30 (QLQ-C30)
- time Frame
- Up to 2.5 years
- description
- Changes from baseline in the EORTC QLQ-OG25 scores
- measure
- HRQoL as assessed by the EORTC Quality of Life Questionnaire (oesophago-gastric module) OG25 (QLQ-OG25)
- time Frame
- Up to 2.5 years
- description
- Changes from baseline in the EORTC EQ-5D-5L questionnaire scores
- measure
- HRQoL as assessed by the EuroQol 5-dimensions 5-levels (EQ-5D-5L) questionnaire
- time Frame
- Up to 2.5 years
Full study description
- brief Summary
- This study is being done to find out if zanidatamab, when given with chemotherapy plus or minus tislelizumab, is safe and works better than trastuzumab given with chemotherapy. The patients in this study will have advanced human epidermal growth factor 2 (HER2)-positive stomach and esophageal cancers that are no longer treatable with surgery (unresectable) or chemoradiation, and/or have grown or spread to other parts of the body (metastatic).
Source references
- references
- citation
- Shitara K, Elimova E, Liu T, Tabernero J, Lee KW, Schenker M, Tebbutt NC, Ajani J, Salimin N, Ku G, Gwang Kim J, Ales Diaz I, Zhang J, Pietrantonio F, Bai LY, Le Sourd S, Zhao J, Hierro C, Kiberu A, Van Herpe F, Bao Y, Zhang H, Yang L, Li V, Gartner EM, Chen Y, Grim J, Rha SY, Shen L; HERIZON-GEA-01 Investigators. Zanidatamab with and without Tislelizumab in HER2-Positive Gastroesophageal Cancer. N Engl J Med. 2026 May 28;394(20):2002-2014. doi: 10.1056/NEJMoa2517729.
- pmid
- 42202319
- type
- DERIVED
- citation
- Lee KW, Bai LY, Jung M, Ying J, Im YH, Oh DY, Cho JY, Oh SC, Chao Y, Kim JW, Chen Y, Li V, Chen S, Kang YK. Phase Ib/II Study of Zanidatamab in Combination with Tislelizumab and Chemotherapy in First-Line HER2-Positive Gastric/Gastroesophageal Junction Adenocarcinoma. Clin Cancer Res. 2026 Jan 16;32(2):312-323. doi: 10.1158/1078-0432.CCR-24-4295.
- pmid
- 41324998
- type
- DERIVED
- citation
- Yu J, Mehta R. Biomarker-Driven Approach to the Treatment of Metastatic Gastric or Gastroesophageal Adenocarcinoma. J Natl Compr Canc Netw. 2025 May;23(5):e257036. doi: 10.6004/jnccn.2025.7036.
- pmid
- 40341124
- type
- DERIVED
- citation
- Tabernero J, Shen L, Elimova E, Ku G, Liu T, Shitara K, Lin X, Boyken L, Li H, Grim J, Ajani J. HERIZON-GEA-01: Zanidatamab + chemo +/- tislelizumab for 1L treatment of HER2-positive gastroesophageal adenocarcinoma. Future Oncol. 2022 Sep;18(29):3255-3266. doi: 10.2217/fon-2022-0595. Epub 2022 Aug 24.
- pmid
- 36000541
- type
- DERIVED
Source notices and limitations
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Preserved source evidence · Not medical advice