Updated results of HLX22 plus trastuzumab and XELOX for first-line treatment of human epidermal growth factor receptor 2 (HER2)–positive locally advanced or metastatic gastric/gastroesophageal junction cancer (G/GEJC).

Abstract

e16021 Background: HER2-positive (HER2+) G/GEJC accounts for 12–23% of G/GEJC cases. Survival outcomes with combined treatment of trastuzumab and chemotherapy remain unsatisfactory. This phase 2 study is evaluating HLX22 and trastuzumab, which target different HER2 epitopes, combined with XELOX chemotherapy as first-line treatment for patients with advanced G/GEJC. Following the report at ASCO GI Cancers Symposium 2025, here we present updated efficacy and safety results at extended follow-up. Methods: Patients with locally advanced or metastatic HER2+ G/GEJC and no prior systemic antitumor therapy were enrolled, and randomized in a 1: 1 ratio 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 December 6, 2024, 62 patients were randomized to the respective groups (31 vs 31), of whom 51 (82.3%) were male. Median follow-up duration was 28.5 and 28.7 months for the respective groups. Major efficacy findings are shown in Table 1. Treatment-emergent adverse events (TEAEs) were reported in 30 (96.8%) and 31 (100%) patients, respectively. TEAEs of grade 3 or higher were observed in 17 (54.8%) and 15 (48.4%) patients. HLX22- or placebo-related TEAE leading to death occurred in 1 (3.2%) patient in the placebo + trastuzumab + XELOX group. One patient (3.2%) in each group reported HLX22/placebo-related TEAEs leading to treatment discontinuation. Conclusions: Combination of chemotherapy and dual HER2 blockade with HLX22 and trastuzumab conferred survival benefit to HER2-positive G/GEJC patients along with a manageable safety profile. Clinical trial information: NCT04908813 . Updated efficacy*. HLX22 + trastuzumab + XELOX (n=31) placebo + trastuzumab + XELOX (n=31) Median PFS, months (95% CI) NR (16.2, NE) 8.3 (5.7, 21.4) HR (95% CI) 0.2 (0.09, 0.54) 12-month PFS rate (95% CI) 77.1 (56.0, 89.0) 40.8 (20.4, 60.4) 24-month PFS rate (95% CI) 54.8 (27.3, 75.7) 17.5 (1.6, 48.0) Confirmed ORR, % (95% CI) 87.1 (70.2, 96.4) 80.6 (62.5, 92.5) Median OS, months (95% CI) NR (16.2, NE) 16.4 (10.7, NE) HR (95% CI) 0.6 (0.28, 1.21) Median confirmed DOR, months (95% CI) NR (13.2, NE) 9.7 (4.6, NE) HR (95% CI) 0.2 (0.07, 0.52) CI, confidence interval. DOR, duration of response. NE, not evaluable. NR, not reached. OS, overall survival. PFS, ORR, and DOR were based on IRRC assessments. *The cutoff date for IRRC-assessed results was October 31, 2024.