Esophageal Adenocarcinoma, Gastric Neoplasms, Gastroesophageal Adenocarcinoma
Conditions
Keywords
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, JZP598
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).
Interventions
DRUGZanidatamab
Administered IV
DRUGTislelizumab
Administered IV
DRUGTrastuzumab
Administered intravenously (IV)
DRUGCapecitabine
Administered orally (PO bid)
DRUGOxaliplatin
Administered IV
DRUGCisplatin
Administered IV
DRUG5-Fluorouracil
Administered IV
Sponsors
Jazz Pharmaceuticals
BeOne Medicines LTD
BeOne Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
multi-cohort, open-label, multicenter study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Estonia, France, Georgia, Germany, Greece, Guatemala, India, Ireland, Italy, Japan, Malaysia, Mexico, Netherlands, Poland, Portugal, Romania, Serbia, Singapore, South Africa, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom
Outcome results
None listed