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

作者：Keun‐Wook Lee, Li‐Yuan Bai, Minkyu Jung, Jieer Ying, Young‐Hyuck Im, Do‐Youn Oh, Jae Yong Cho, Sang Cheul Oh, Yee Chao, Jin Won Kim, Ye Chen, Vincent Li, Shengnan Chen, Yoon‐Koo Kang · 发表于：Clinical Cancer Research · 年份：2025 · DOI：10.1158/1078-0432.ccr-24-4295 · 被引用次数：4 · 研究领域：Gastric Cancer Management and Outcomes、HER2/EGFR in Cancer Research、Peptidase Inhibition and Analysis

PURPOSE: This phase Ib/II trial (NCT04276493) assessed the antitumor activity, safety, and pharmacokinetics (PK) of zanidatamab in combination with tislelizumab and chemotherapy in patients 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 = 19; cohort B, n = 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...