Cancer
Conditions
Interventions
Active Comparator
Control
tislelizumab Zanidatamab and Transtuzumab
Sponsors
Jazz Pharmaceuticals Ireland Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion 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
Exclusion criteria: 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 |
|---|---|
| Progression-free survival (PFS) by BICR;Overall survival;Progression-free survival (PFS) by BICR;Overall survival | — |
Secondary
| Measure | Time frame |
|---|---|
| Confirmed objective response rate (ORR) by BICR;Duration of response (DOR) by BICR ;PFS per Investigator assessment;Confirmed ORR per Investigator assessment ;DOR per Investigator assessment;Assessment of Contribution of Components based on Progression-free Survival (PFS) by BICR;Assessment of Contribution of Components based on Overall Survival ;Confirmed objective response rate (ORR) by BICR;Duration of response (DOR) by BICR ;PFS per Investigator assessment;Confirmed ORR per Investigator assessment ;DOR per Investigator assessment;Assessment of Contribution of Components based on Progression-free Survival (PFS) by BICR;Assessment of Contribution of Components based on Overall Survival ;Incidence of adverse events;Incidence of clinical laboratory abnormalities;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);HRQoL as assessed by the EORTC Quality of Life Questionnaire (oesophago-gastric module) OG25 (QLQ-OG25);HRQoL as assessed by the EuroQol 5-dimensions 5-levels (EQ-5D-5L) questionnaire;Serum concentration of zanidatamab and tislelizumab;Incidence of anti-drug antibodies (ADAs) | — |
Countries
Kenya, Uganda
Contacts
Public ContactHaj Manel
Principal Investigator
Outcome results
None listed