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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05152147
Recruitment Status : Recruiting
First Posted : December 9, 2021
Last Update Posted : April 5, 2023
Sponsor:
Collaborator:
BeiGene, Ltd.
Information provided by (Responsible Party):
Zymeworks Inc.

Study Description
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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).


Condition or disease Intervention/treatment Phase
Gastric Neoplasms Gastroesophageal Adenocarcinoma Esophageal Adenocarcinoma Drug: Zanidatamab Drug: Tislelizumab Drug: Trastuzumab Drug: Capecitabine Drug: Oxaliplatin Drug: Cisplatin Drug: 5-Fluorouracil Diagnostic Test: In situ hybridization (ISH)-based companion diagnostic assay Diagnostic Test: Immunohistochemistry (IHC)-based companion diagnostic assay Phase 3

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 714 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: multi-cohort, open-label, multicenter study
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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)
Actual Study Start Date : December 2, 2021
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : July 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Arm A
Trastuzumab (Herceptin®) plus physician's choice of capecitabine plus oxaliplatin (CAPOX) or 5-fluorouracil (5-FU) plus cisplatin (FP)
 Drug: Trastuzumab
Administered intravenously (IV)
Other Name: Herceptin®

Drug: Capecitabine
Administered orally (PO bid)

Drug: Oxaliplatin
Administered IV

Drug: Cisplatin
Administered IV

Drug: 5-Fluorouracil
Administered IV

Diagnostic Test: In situ hybridization (ISH)-based companion diagnostic assay
Subjects will be tested for HER2 gene-amplification using the ISH-based companion diagnostic assay

Diagnostic Test: Immunohistochemistry (IHC)-based companion diagnostic assay
Subjects will be tested for HER2 protein-expression using the IHC-based companion diagnostic assay
Experimental: Arm B
Zanidatamab plus physician's choice of CAPOX or FP
 Drug: Zanidatamab
Administered IV
Other Name: ZW25

Drug: Capecitabine
Administered orally (PO bid)

Drug: Oxaliplatin
Administered IV

Drug: Cisplatin
Administered IV

Drug: 5-Fluorouracil
Administered IV

Diagnostic Test: In situ hybridization (ISH)-based companion diagnostic assay
Subjects will be tested for HER2 gene-amplification using the ISH-based companion diagnostic assay

Diagnostic Test: Immunohistochemistry (IHC)-based companion diagnostic assay
Subjects will be tested for HER2 protein-expression using the IHC-based companion diagnostic assay
Experimental: Arm C
Zanidatamab and tislelizumab plus physician's choice of CAPOX or FP
 Drug: Zanidatamab
Administered IV
Other Name: ZW25

Drug: Tislelizumab
Administered IV

Drug: Capecitabine
Administered orally (PO bid)

Drug: Oxaliplatin
Administered IV

Drug: Cisplatin
Administered IV

Drug: 5-Fluorouracil
Administered IV

Diagnostic Test: In situ hybridization (ISH)-based companion diagnostic assay
Subjects will be tested for HER2 gene-amplification using the ISH-based companion diagnostic assay

Diagnostic Test: Immunohistochemistry (IHC)-based companion diagnostic assay
Subjects will be tested for HER2 protein-expression using the IHC-based companion diagnostic assay


Outcome Measures
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Primary Outcome Measures :
  1. 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

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


Secondary Outcome Measures :
  1. Confirmed objective response rate (ORR) by BICR [ Time Frame: Up to 2.5 years ]
    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

  2. Duration of response (DOR) by BICR [ Time Frame: Up to 2.5 years ]
    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

  3. PFS per Investigator assessment [ Time Frame: Up to 2.5 years ]
    The time from randomization to the date of documented disease progression (per RECIST 1.1) as assessed by Investigator or death from any cause

  4. ORR per Investigator assessment [ Time Frame: Up to 2.5 years ]
    Number of patients who achieved a best overall response of CR or PR as determined per RECIST 1.1 as assessed by Investigator

  5. DOR per Investigator assessment [ Time Frame: Up to 2.5 years ]
    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

  6. Incidence of adverse events [ Time Frame: Up to 2 years ]
    Number of subjects who experienced adverse events or serious adverse events

  7. Incidence of clinical laboratory abnormalities [ Time Frame: Up to 2 years ]
    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

  8. 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 ]
    Changes from baseline in the EORTC QLQ-C30 scores

  9. HRQoL as assessed by the EORTC Quality of Life Questionnaire (oesophago-gastric module) OG25 (QLQ-OG25) [ Time Frame: Up to 2.5 years ]
    Changes from baseline in the EORTC QLQ-OG25 scores

  10. HRQoL as assessed by the EuroQol 5-dimensions 5-levels (EQ-5D-5L) questionnaire [ Time Frame: Up to 2.5 years ]
    Changes from baseline in the EORTC EQ-5D-5L questionnaire scores

  11. Serum concentration of zanidatamab, tislelizumab, and trastuzumab [ Time Frame: Up to 2 years ]
  12. Incidence of anti-drug antibodies (ADAs) [ Time Frame: Up to 2 years ]
    Number of patients who develop ADAs


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05152147


Contacts
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Contact: Zymeworks Clinical Trial Resource 206-237-1030 medinfo@zymeworks.com

Locations
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Sponsors and Collaborators
Zymeworks Inc.
BeiGene, Ltd.
Investigators
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Study Director: Jonathan Grim, MD, PhD Zymeworks Inc.
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Zymeworks Inc.
ClinicalTrials.gov Identifier: NCT05152147    
Other Study ID Numbers: ZWI-ZW25-301
2021-000296-36 ( EudraCT Number )
First Posted: December 9, 2021    Key Record Dates
Last Update Posted: April 5, 2023
Last Verified: April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Keywords provided by Zymeworks Inc.:
HER2
Bispecific antibody
Biparatopic antibody
Immunotherapy
Gastric cancers
Esophageal cancers
Chemotherapy
FP
Capecitabine
 Cisplatin
5-FU
Oxaliplatin
Gastroesophageal adenocarcinoma
CAPOX
Programmed cell death receptor 1 (PD-1)
Anti-PD-1
Anti PD-1
Additional relevant MeSH terms:
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Adenocarcinoma
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Fluorouracil
 Capecitabine
Oxaliplatin
Trastuzumab
Tislelizumab
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological