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

Phase 3Active Not RecruitingNCT05152147

Jazz Pharmaceuticals920 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

920

Conditions

Gastric Neoplasms Gastroesophageal Adenocarcinoma Esophageal Adenocarcinoma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

Progression-free survival (PFS) by BICR

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

Time frame: Up to 2.5 years

Overall survival

The time from randomization to death due to any cause

Time frame: Up to 3.5 years

Secondary Outcomes

Confirmed objective response rate (ORR) by BICR

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

Time frame: Up to 2.5 years

Duration of response (DOR) by BICR

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

Time frame: Up to 2.5 years

PFS per Investigator assessment

The time from randomization to the date of documented disease progression (per RECIST 1.1) as assessed by Investigator or death from any cause

Time frame: Up to 2.5 years

Confirmed ORR per Investigator assessment

Number of patients who achieved a best overall response of CR or PR as determined per RECIST 1.1 as assessed by Investigator

Time frame: Up to 2.5 years

DOR per Investigator assessment

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

Time frame: Up to 2.5 years

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

Time frame: Up to 2.5 years

Assessment of Contribution of Components based on Overall Survival

The time from randomization to death due to any cause

Time frame: Up to 3.5 years

Incidence of adverse events

Number of subjects who experienced adverse events or serious adverse events

Time frame: Up to 2 years

Incidence of clinical laboratory abnormalities

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

Time frame: Up to 2 years

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)

Changes from baseline in the EORTC QLQ-C30 scores

Time frame: Up to 2.5 years

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

Changes from baseline in the EORTC QLQ-OG25 scores

Time frame: Up to 2.5 years

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

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

Time frame: Up to 2.5 years

Serum concentration of zanidatamab and tislelizumab

Time frame: Up to 2 years

Incidence of anti-drug antibodies (ADAs)

Number of patients who develop ADAs

Time frame: Up to 2 years

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

Overview

Conditions

Interventions

Eligibility

Locations (226)

Outcomes

Primary Outcomes

Secondary Outcomes