HLX22 plus trastuzumab and XELOX for first-line treatment of HER2-positive locally advanced or metastatic gastric/gastroesophageal junction cancer (G/GEJC): Updated results with additional patients.
Authors: Jin Li, Ning Li, Mudan Yang, Yanqiao Zhang, Diansheng Zhong, Meng Qiu, Linzhi Lu, Xiaoming Hou, Yanru Qin, Guoping Sun, Jun Deng, Zimin Liu, Bo Liu, Yuntao Ma, Jingdong Zhang, Futang Yang, Haoyu Yu, Jing Li, Qingyu Wang, Jun Zhu
Journal: Journal of Clinical Oncology (2025)

440 Background: Approximately 12–23% G/GEJC patients have human epidermal growth factor receptor 2 (HER2)-positive disease. Despite survival benefit from combination therapy with trastuzumab and chemotherapy, the prognosis remains unsatisfactory; more effective treatments are needed. This phase 2 study is evaluating the combination of HLX22 (an anti-HER2 monoclonal antibody targeting a different epitope than trastuzumab), trastuzumab, and XELOX chemotherapy as first-line treatment for patients with advanced/metastatic G/GEJC. Following the most recent report of 17 to 18 patients in each group at ASCO 2024 Annual Meeting, herein we present the updated efficacy and safety results with 31 patients in each group. Methods: Patients with locally advanced or metastatic HER2-positive G/GEJC and no prior systemic antitumor therapy were enrolled. Herein reported are results from Stage 2 of the study. Eligible patients were randomized to receive either HLX22 + trastuzumab + XELOX or placebo + trastuzumab + XELOX in 3-week cycles. Primary endpoints were independent radiology review committee (IRRC)-assessed progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints included other efficacy and safety endpoints. Results: As of June 30, 2024, 62 patients were randomized to the respective groups (31 vs 31), of whom 51 (82.3%) patients were male. Median follow-up duration was 20.3 and 24.0 months for the respective groups. The efficacy results are shown in the table. Treatment-emergent adverse events (TEAEs) were reported in 30 (96.8%) and 31 (100%) patients, and HLX22- or placebo-related TEAEs of grade 3 or higher were reported in 9 (29.0%) and 6 (19.4%) patients in the respective groups. One patient (3.2%) in the placebo + trastuzumab + XELOX group had a grade 5 HLX22-/placebo-related TEAE. Conclusions: With a manageable safety profile, the addition of HLX22 to first-line treatment with trastuzumab plus XELOX conferred survival benefit for HER2-positive G/GEJC patients. Clinical trial information: NCT04908813 . Updated efficacy, IRRC-assessed. HLX22 + trastuzumab + XELOX (n=31) placebo + trastuzumab + XELOX (n=31) Median PFS, months (95% CI) NR (23.49, NE) 8.3 (5.7, 12.7) HR (95% CI) 0.2 (0.06, 0.45) - 12-month PFS rate (95% CI) 73.8 (50.3, 87.4) 34.2 (12.0, 58.1) 24-month PFS rate (95% CI) 61.5 (30.4, 82.0) 24.0 (10.3, 27.3) Confirmed ORR, % (95% CI) 87.1 (70.2, 96.4) 80.6 (62.5, 92.5) Week 48 ORR, % (95% CI) 38.7 (21.8, 57.8) 9.7 (2.0, 25.8) Median OS, months (95% CI) NR (17.6, NE) 22.0 (10.6, NE) HR (95% CI) 0.5 (0.20, 1.21) - Median DOR, months (95% CI) NR (22.1, NE) 9.7 (4.6, 20.0) HR (95% CI) 0.1 (0.04, 0.41) - CI, confidence interval. NE, not evaluable. NR, not reached.