A Study of Zanidatamab in Combination With Chemotherapy Plus or Minus Tislelizumab in Patients With HER2-positive Advanced or Metastatic Gastric and Esophageal Cancers
- Conditions
- Gastric NeoplasmsGastroesophageal AdenocarcinomaEsophageal Adenocarcinoma
- Interventions
- Registration Number
- NCT05152147
- Lead Sponsor
- Jazz Pharmaceuticals
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 920
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm C Oxaliplatin Zanidatamab and tislelizumab plus physician's choice of CAPOX or FP Arm C Cisplatin Zanidatamab and tislelizumab plus physician's choice of CAPOX or FP Arm C 5-Fluorouracil Zanidatamab and tislelizumab plus physician's choice of CAPOX or FP Arm B Zanidatamab Zanidatamab plus physician's choice of CAPOX or FP Arm A Trastuzumab Trastuzumab (Herceptin®) plus physician's choice of capecitabine plus oxaliplatin (CAPOX) or 5-fluorouracil (5-FU) plus cisplatin (FP) Arm A Capecitabine Trastuzumab (Herceptin®) plus physician's choice of capecitabine plus oxaliplatin (CAPOX) or 5-fluorouracil (5-FU) plus cisplatin (FP) Arm A Oxaliplatin Trastuzumab (Herceptin®) plus physician's choice of capecitabine plus oxaliplatin (CAPOX) or 5-fluorouracil (5-FU) plus cisplatin (FP) Arm A Cisplatin Trastuzumab (Herceptin®) plus physician's choice of capecitabine plus oxaliplatin (CAPOX) or 5-fluorouracil (5-FU) plus cisplatin (FP) Arm A 5-Fluorouracil Trastuzumab (Herceptin®) plus physician's choice of capecitabine plus oxaliplatin (CAPOX) or 5-fluorouracil (5-FU) plus cisplatin (FP) Arm B Capecitabine Zanidatamab plus physician's choice of CAPOX or FP Arm B Oxaliplatin Zanidatamab plus physician's choice of CAPOX or FP Arm B Cisplatin Zanidatamab plus physician's choice of CAPOX or FP Arm B 5-Fluorouracil Zanidatamab plus physician's choice of CAPOX or FP Arm C Zanidatamab Zanidatamab and tislelizumab plus physician's choice of CAPOX or FP Arm C Tislelizumab Zanidatamab and tislelizumab plus physician's choice of CAPOX or FP Arm C Capecitabine Zanidatamab and tislelizumab plus physician's choice of CAPOX or FP
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) by BICR 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
Overall survival Up to 3.5 years The time from randomization to death due to any cause
- Secondary Outcome Measures
Name Time Method Confirmed objective response rate (ORR) by BICR 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
Duration of response (DOR) by BICR 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
PFS per Investigator assessment 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
Confirmed ORR per Investigator assessment 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
DOR per Investigator assessment 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
Assessment of Contribution of Components based on Progression-free Survival (PFS) by BICR 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
Assessment of Contribution of Components based on Overall Survival Up to 3.5 years The time from randomization to death due to any cause
Incidence of adverse events Up to 2 years Number of subjects who experienced adverse events or serious adverse events
Incidence of clinical laboratory abnormalities 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
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) Up to 2.5 years Changes from baseline in the EORTC QLQ-C30 scores
HRQoL as assessed by the EORTC Quality of Life Questionnaire (oesophago-gastric module) OG25 (QLQ-OG25) Up to 2.5 years Changes from baseline in the EORTC QLQ-OG25 scores
HRQoL as assessed by the EuroQol 5-dimensions 5-levels (EQ-5D-5L) questionnaire Up to 2.5 years Changes from baseline in the EORTC EQ-5D-5L questionnaire scores
Serum concentration of zanidatamab and tislelizumab Up to 2 years Incidence of anti-drug antibodies (ADAs) Up to 2 years Number of patients who develop ADAs
Trial Locations
- Locations (226)
Hospital de Gastroenterología Dr Bonorino Udaondo
🇦🇷Buenos Aires, Argentina
Instituto de Investigaciones Metabólicas - IDIM
🇦🇷Buenos Aires, Argentina
Hospital Italiano de Buenos Aires
🇦🇷Buenos Aires, Argentina
Fundación Centro de Medicina Nuclear y Molecular ER
🇦🇷Córdoba, Argentina
Centro Médico Privado CEMAIC
🇦🇷Córdoba, Argentina
Centro de Investigación Pergamino S.A.
🇦🇷Pergamino, Argentina
Centro de Investigación Clínica - Clínica Viedma
🇦🇷Viedma, Argentina
Flinders Medical Centre
🇦🇺Bedford Park, Australia
Austin Health
🇦🇺Heidelberg, Australia
Liverpool Hospital
🇦🇺Liverpool, Australia
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