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

NCT05152147
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Phase
Phase 3
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Recruitment status
Active, not recruiting
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Participants
920
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Lead sponsor
Jazz Pharmaceuticals
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Start date
2021-12-02
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Number of sites
227
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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).
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Acronym
HERIZON-GEA-01
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Short title
A Study of Zanidatamab in Combination With Chemotherapy Plus or Minus Tislelizumab in Patients With HER2-positive Advanced or Metastatic Gastric and Esophageal Cancers
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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)
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Active, not recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2027-09-30
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First posted
2021-12-09
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Registry last updated
2026-10-20
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Primary completion date
2026-07-15
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Start date
2021-12-02
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Actual participants
920
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Participants
920
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Participant count basis
Actual
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Protocol amendments
11
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Number of sites
227
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Jazz Pharmaceuticals
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05152147
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ClinicalTrials.gov ID
NCT05152147
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
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  1. Progression-free survival (PFS) by BICR

    Timeframe: 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 blinded independent central review (BICR) or death from any cause

  2. Overall survival

    Timeframe: Up to 3.5 years

    The time from randomization to death due to any cause

  1. Confirmed objective response rate (ORR) by BICR

    Timeframe: 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

    Timeframe: 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

    Timeframe: 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. Confirmed ORR per Investigator assessment

    Timeframe: 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

    Timeframe: 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. Assessment of Contribution of Components based on Progression-free Survival (PFS) by BICR

    Timeframe: 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 blinded independent central review (BICR) or death from any cause

  7. Assessment of Contribution of Components based on Overall Survival

    Timeframe: Up to 3.5 years

    The time from randomization to death due to any cause

  8. Incidence of adverse events

    Timeframe: Up to 2 years

    Number of subjects who experienced adverse events or serious adverse events

  9. Incidence of clinical laboratory abnormalities

    Timeframe: 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

  10. 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)

    Timeframe: Up to 2.5 years

    Changes from baseline in the EORTC QLQ-C30 scores

  11. HRQoL as assessed by the EORTC Quality of Life Questionnaire (oesophago-gastric module) OG25 (QLQ-OG25)

    Timeframe: Up to 2.5 years

    Changes from baseline in the EORTC QLQ-OG25 scores

  12. HRQoL as assessed by the EuroQol 5-dimensions 5-levels (EQ-5D-5L) questionnaire

    Timeframe: Up to 2.5 years

    Changes from baseline in the EORTC EQ-5D-5L questionnaire scores

  13. Serum concentration of zanidatamab and tislelizumab

    Timeframe: Up to 2 years

  14. Incidence of anti-drug antibodies (ADAs)

    Timeframe: Up to 2 years

    Number of patients who develop ADAs

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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)
Sources for eligibility
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  • Buenos Aires, Argentina
  • Instituto de Investigaciones Metabólicas - IDIMBuenos Aires, Argentina
  • Hospital Italiano de Buenos AiresBuenos Aires, Argentina
  • Fundación Centro de Medicina Nuclear y Molecular ERCórdoba, Argentina
  • Centro Médico Privado CEMAICCórdoba, Argentina
  • Centro de Investigación Pergamino S.A.Pergamino, Argentina
  • Centro de Investigación Clínica - Clínica ViedmaViedma, Argentina
  • Flinders Medical CentreBedford Park, Australia
  • Austin HealthHeidelberg, Australia
  • Liverpool HospitalLiverpool, Australia
  • Fiona Stanley HospitalMurdoch, Australia
  • Imelda VZWBonheiden, Belgium
  • Cliniques Universitaires Saint-LucBrussels, Belgium
  • UZ GentGhent, Belgium
  • UZ LeuvenLeuven, Belgium
  • CHU de LiègeLiège, Belgium
  • Centro Integrado de Pesquisa - CIPBarretos, Brazil
  • Fundação Pio XII Hospital de Câncer de BarretosBarretos, Brazil
  • Cenantron - Centro Avancado de Tratamento Oncologico LtdaBelo Horizonte, Brazil
  • Centro de Pesquisas Clínicas/Fundação Doutor Amaral CarvalhoBrasília, Brazil
  • Instituto Do Câncer Do Ceará ICCFortaleza, Brazil
  • Hospital de Clinicas de Porto Alegre (HCPA) - PPDSPorto Alegre, Brazil
  • Irmandade Da Santa Casa de Misericordia de Porto AlegrePorto Alegre, Brazil
  • Hospital Nossa Senhora Da ConceiçãoPorto Alegre, Brazil
  • Núcleo de Pesquisa Clínica da Rede São CamiloSanto André, Brazil

And 202 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2023
  • 2023-510319-20-00
  • 2021-000296-36
  • jRCT2061230026
Sources for references
clinicaltrials.gov

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