Clin Cancer Res. 2026;32(2):312-323.

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

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제1저자 이근욱 · 교신저자 이근욱

PMID 41324998 PMC12809114 DOI 10.1158/1078-0432.CCR-24-4295 IF 10.9 혈액종양내과

소속 (12)

Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Division of Hematology and Oncology, China Medical University Hospital and China Medical University, Taichung, Taiwan.
Division of Medical Oncology, Yonsei University College of Medicine, Yonsei Cancer Center, Seoul, Republic of Korea.
Department of Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
Department of Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Republic of Korea.
Department of Oncology, Gangnam Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.
Department of Oncology, Korea University Guro Hospital, Seoul, Republic of Korea.
Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.
Clinical Development, BeOne Medicines Ltd. (Beijing) Co., Ltd., Beijing, China.
Global Statistics and Data Science, BeOne Medicines Ltd. (Shanghai) Co., Ltd., Shanghai, China.
Department of Oncology, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea.

Abstract

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 grade ≥3 were reported in 22 (66.7%) patients; diarrhea was the most common (27.3%).

CONCLUSIONS Zanidatamab, in combination with tislelizumab and 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).

Figures

**Figure 1.** Data cutoff: December 7, 2023. Efficacy-evaluable analysis set. A, Best percent change from baseline in target lesion sum of diameter. Best overall response per investigator assessment. B, Duration of treatment and best overall response. (F)ISH, (fluorescence) *in situ* hybridization; NA, not applicable; NE, not estimable.

**Figure 2.** PFS (A), OS (B), and DoR (C). Data cutoff: December 7, 2023. Efficacy-evaluable analysis set (A) and (C) and safety analysis set (B). PFS, OS, and DoR per investigator assessment. The median values were estimated by the Kaplan–Meier method with 95% CI estimated using the Brookmeyer–Crowley method with log–log transformation. Landmark rates were estimated using the Kaplan–Meier method with 95% CI estimated using the Greenwood formula. NE, not estimable.

그림 출처: PubMed Central 공개 논문 (PMC12809114)

Comment · 정정

Comment in J Gastrointest Oncol. 2026 Aug 31;17(4):276. doi: 10.21037/jgo-2026-0471.

Conflict of interest statement

K.-W. Lee reports grants from BeOne Medicines Ltd. (to institution for conducting clinical trials) during the conduct of the study; grants from ALX Oncology, Amgen, Arcus Biosciences, Astellas Pharma, AstraZeneca, Bolt Biotherapeutics, Daiichi Sankyo, Elevar Therapeutics, Erasca, Exelixis, Genome & Company, GlaxoSmithKline, IgM Biosciences, Ildong Pharmaceutical, InventisBio, Jazz Pharmaceuticals, Leap Therapeutics, MacroGenics, Medicenna, MedPacto, Metafines, Merck KGaA, MSD, Ono Pharmaceutical, Panolos Bioscience, Roche, Seagen, Taiho Pharmaceutical, TRIO Oncology, Trishula Therapeutics, Wellmarker Bio, and Y-BIOLOGICS (research funding to institution for conducting clinical trials), personal fees from Astellas Pharma, Bayer, Daiichi Sankyo, Merck KGaA, and Sanofi/Aventis (honoraria for lectures or presentations), and personal fees from AbbVie, Astellas Pharma, Daiichi Sankyo, Metafines, and MSD (consulting fees) outside the submitted work; and an uncompensated relationship with ALX Oncology for participation on a data safety monitoring or advisory board. L.-Y. Bai reports institutional research funding for conducting clinical trials from BeOne Medicines Ltd. in relation to this manuscript. D.-Y. Oh reports research funding from Array BioPharma, AstraZeneca, BeOne Medicines Ltd., Handok, Lilly, MSD, Novartis, and Servier; and consulting fees from Arcus Biosciences, ASLAN Pharmaceuticals, AstraZeneca, Basilea, Bayer, BeOne Medicines Ltd., Celgene, Genentech/Roche, Halozyme, IQVIA, Merck Serono, MSD Oncology, Novartis, Taiho Pharmaceutical, Turning Point Therapeutics, and Zymeworks. J.-W. Kim reports research grants from Inno.N and Jeil Pharmaceutical; and consulting fees from AstraZeneca, BeOne Medicines Ltd., Beyond Bio, Bristol Myers Squibb/Celgene, Eisai, GC Cell, MSD, ONO, Sanofi-Aventis, Servier, and TCUBEit. Y. Chen, V. Li, and S. Chen are employed by BeOne Medicines Ltd. and may hold stock or other ownership. Y.-K. Kang reports consulting fees from ALX Oncology, Amgen, Blueprint, BMS, Daehwa, Liscure, Macrogenics, Merck, Novartis, Roche, and Surface Oncology. No disclosures were reported by the other authors.

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