Gastroesophageal Adenocarcinoma (GEA) MedDRA version: 22.0 Level: LLT Classification code 10082464 Term: Advanced gastric carcinoma System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10055458 Term: Esophageal adenocarcinoma System Organ Class: 100000004864
Conditions
Sponsors
Zymeworks Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.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 ISHpositivity per central assessment. Subjects with esophageal adenocarcinoma must not be eligible for combined chemoradiotherapy at the time of enrollment. 2.Assessable (measurable or non-measurable) disease as defined by RECIST 1.1. 3.Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, assessed within 3 days prior to randomization 4.Adequate organ function 5.Left ventricular ejection fraction (LVEF) = 50% as determined by either echocardiogram or multiple gated acquisition scan (MUGA) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 321 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 828
Exclusion criteria
Exclusion criteria: 1.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. 2.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. 3.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). 4.Known history of or ongoing leptomeningeal disease (LMD). 5.Prior or concurrent invasive malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen. 6.Known active hepatitis 7.Any history of human immunodeficiency virus (HIV) infection 8.Known SARS-CoV-2 infection; subjects with prior infection that has resolved per local institutions’ requirements and screening guidance are eligible 9.Clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension or any history of symptomatic congestive heart failure (CHF). 10.QTc Fridericia (QTcF) > 470 ms. 11.Ongoing Grade 2 or greater peripheral neuropathy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: ?To compare the efficacy of zanidatamab in combination with chemotherapy or in combination with chemotherapy and tislelizumab to the efficacy of trastuzumab in combination with chemotherapy in subjects with unresectable locally advanced, recurrent or metastatic HER2 positive GEA;Secondary Objective: ?To further compare the efficacy of zanidatamab in combination with chemotherapy or chemotherapy and tislelizumab to chemotherapy with trastuzumab ?To evaluate the safety and tolerability of zanidatamab in combination with chemotherapy or chemotherapy and tislelizumab ?To evaluate the effect of zanidatamab in combination with chemotherapy or chemotherapy and tislelizumab on health-related quality of life (HRQoL) ?To evaluate the pharmacokinetics (PK) of zanidatamab in combination with chemotherapy or chemotherapy and tislelizumab ?To evaluate the PK of tislelizumab in combination with chemotherapy and zanidatamab ?To evaluate the immunogenicity of zanidatamab in combination with chemotherapy or chemotherapy and tislelizumab ?To evaluate the immunogenicity of tislelizumab in combination with chemotherapy and zanidatamab;Primary end point(s): ?Progression-free survival (PFS) by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), assessed by blinded independent central review (BICR) ?Overall survival (OS);Timepoint(s) of evaluation of this end point: The primary PFS analysis and interim OS analysis are expected to occur approximately 1 month after the last subject is randomized. The primary analysis of OS is expected to be reached 14 months after the last subject is randomized. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ?Confirmed objective response rate (ORR) by RECIST 1.1, assessed by BICR ?Duration of response (DOR) by RECIST 1.1, assessed by BICR ?PFS by RECIST 1.1, per investigator assessment ?ORR by RECIST 1.1, per investigator assessment ?DOR by RECIST 1.1, per investigator assessment ?Frequency, type, severity, seriousness, and relatedness of adverse events (AEs) ?Frequency and severity of clinical laboratory abnormalities ?Change from baseline in health economics and outcomes research / patient-reported outcomes (HEOR/PRO) parameters ?PK parameters for zanidatamab ?PK parameters for tislelizumab ?Frequency, duration, and time of onset of anti zanidatamab antibodies and neutralizing antibodies, if applicable ?Frequency, duration, and time of onset of anti tislelizumab antibodies and neutralizing antibodies, if applicable;Timepoint(s) of evaluation of this end point: The primary PFS analysis and interim OS analysis are expected to occur approximately 1 month after the last subject is randomized. The primary analysis of OS is expected to be reached 14 months after the last subject is randomized. | — |
Countries
Argentina, Belgium, Brazil, Canada, Chile, China, France, Germany, Greece, Italy, Korea, Democratic People's Republic of, Netherlands, Peru, Poland, Portugal, Romania, Russian Federation, Serbia, Spain, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactProject Management
PPD
Outcome results
None listed