Phase Ib/II Study of Zanidatamab in Combination with Tislelizumab and Chemotherapy in First-Line HER2-Positive Gastric/Gastroesophageal Junction Adenocarcinoma

Q: What was the purpose of the Phase Ib/II trial NCT04276493?

The trial assessed the antitumor activity, safety, and pharmacokinetics of zanidatamab in combination with tislelizumab and chemotherapy in patients with advanced HER2-positive gastric or GEJ adenocarcinoma.

Q: How were patients treated in the study?

Adult patients received zanidatamab i.v. once every 3 weeks (with cohort A vs weight-based cohort B dosing), plus tislelizumab 200 mg i.v. Q3W and standard CAPOX chemotherapy Q3W.

Q: What were the key efficacy and safety findings?

Among 33 treated patients, confirmed objective response rate was 75.8%, with median DoR 23.3 months, PFS 16.7 months, and OS 32.4 months. Treatment-related adverse events were common, with diarrhea (100%) and grade ≥3 AEs in 66.7% of patients; diarrhea was the most frequent grade ≥3 event.

Sep 23, 2026

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Phase Ib/II trial NCT04276493 evaluated zanidatamab combined with tislelizumab and chemotherapy in adults with advanced HER2-positive gastric cancer or gastroesophageal junction cancer. Patients received zanidatamab with weight- or cohort-based dosing, plus tislelizumab 200 mg i.v. Q3W and CAPOX every 3 weeks. Primary outcomes included confirmed objective response rate per RECIST v1.1 and adverse events. In 33 treated patients, cORR reached 75.8%, with median DoR 23.3 months, PFS 16.7 months, and OS 32.4 months. Diarrhea and nausea were frequent, and grade ≥3 AEs occurred in 66.7% overall, supporting further development.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Purpose

Patients and Methods

Treatment regimen and dosing

Endpoints

Results

Conclusions

Introduction

Disease burden and unmet need

HER2 status and prior standards

Phase Ib/II Study of Zanidatamab in Combination with Tislelizumab and Chemotherapy in First-Line HER2-Positive Gastric/Gastroesophageal Junction Adenocarcinoma Keun-Wook Lee1, Li-Yuan Bai2, Minkyu Jung3, Jieer Ying4, Young-Hyuck Im5, Do-Youn Oh6, Jae Yong Cho7, Sang Cheul Oh8, Yee Chao9, Jin Won Kim1, Ye Chen10, Vincent Li10, Shengnan Chen11, and Yoon-Koo Kang12 | | | A | | B | S | | T | R | | A | | C | T | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Purpose: This phase Ib/II trial (NCT04276493) assessed the antitumor activity, safety, and pharmacokinetics (PK) of zanidatamab in combination with tislelizumab and chemotherapy inpatients with advanced HER2-positive (HER2+) gastric cancer/ gastroesophageal junction cancer (GEJC) .
Patients and Methods: Adult patients with previously untreated, unresectable, locally advanced/metastatic HER2+ gastric cancer/GEJC received zanidatamab 30 mg/kg i.v. (cohort A) or zanidatamab 1800 mg i.v. (weight <70 kg)/2,400 mg i.v. (weight ≥70 kg; cohort B) once every 3 weeks (Q3W). Both cohorts received tislelizumab 200 mg i.v. once every 3 weeks and standard chemotherapy [capecitabine and oxaliplatin (CAPOX)] once every 3 weeks. Primary endpoints were investigator-assessed confirmed objective response rate (cORR) per RECIST v1.1, in addition to the frequency and severity of adverse events (AE) and serious AEs. Secondary endpoints included investigator-assessed progression-free survival (PFS), duration of
􀀶 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | response (DoR), overall survival (OS), PK, and immunogenicity of zanidatamab.
Results: As of December 7, 2023, 33 patients (cohort A, n ¼ 19; cohort B, n ¼ 14) received treatment. The confirmed objective response rate was 75.8%; the median duration of response, progression-free survival, and overall survival were 23.3, 16.7, and 32.4 months, respectively. The most common treatment-related AEs (TRAEs) were diarrhea (100%), nausea (63.6%), and decreased appetite (48.5%). Treatment-related AEs of grade ≥3 were reported in 22 (66.7%) patients; diarrhea was the most common (27.3%).
Conclusions: Zanidatamab, in combination with tislelizumaband CAPOX, demonstrated clinically meaningful antitumor activity with a manageable safety profile as first-line therapy for patients with HER2+ gastric cancer/GEJC. These results support a further development of zanidatamab and tislelizumab with chemotherapy in this patient population in the ongoing phase III HERIZON-GEA-01 trial (NCT05152147) . | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Introduction Gastric cancer and gastroesophageal junction cancer (GEJC) are both the fifth most frequently diagnosed cancer and the fifth leading cause of cancer-related deaths globally according to GLOBOCAN 2022 data (1). Incidence rates are higher in Eastern Asia and Eastern Europe compared with North America and Northern Europe (1). Most cases of gastric cancer/GEJC occurring in Western countries are di

FAQs

What was the purpose of the Phase Ib/II trial NCT04276493?

The trial assessed the antitumor activity, safety, and pharmacokinetics of zanidatamab in combination with tislelizumab and chemotherapy in patients with advanced HER2-positive gastric or GEJ adenocarcinoma.

How were patients treated in the study?

Adult patients received zanidatamab i.v. once every 3 weeks (with cohort A vs weight-based cohort B dosing), plus tislelizumab 200 mg i.v. Q3W and standard CAPOX chemotherapy Q3W.

What were the key efficacy and safety findings?

Among 33 treated patients, confirmed objective response rate was 75.8%, with median DoR 23.3 months, PFS 16.7 months, and OS 32.4 months. Treatment-related adverse events were common, with diarrhea (100%) and grade ≥3 AEs in 66.7% of patients; diarrhea was the most frequent grade ≥3 event.

Sep 23, 2026

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