A Randomized Phase 2 Study of HLX22 Plus Trastuzumab Biosimilar HLX02 and XELOX As First-Line Therapy for HER2-positive Advanced Gastric Cancer

Background: Gastric cancer is the fifth most common cancer and the fourth most common cause of cancer death worldwide, yet the prognosis of advanced disease remains poor. Methods: This was a randomized, double-blinded, phase 2 trial (ClinicalTrials.gov: NCT04908813). Patients with locally advanced/metastatic HER2-positive gastric/gastroesophageal junction cancer and no prior systemic antitumor therapy were randomized 1:1:1 to 25 mg/kg HLX22 (a novel anti-HER2 antibody) + HLX02 (trastuzumab biosimilar) + oxaliplatin and capecitabine (XELOX) (group A), 15 mg/kg HLX22 + HLX02 + XELOX (group B), or placebo + HLX02 + XELOX (group C) in 3-week cycles. Primary endpoints were progression-free survival (PFS) and objective response rate (ORR) assessed by independent radiological review committee (IRRC). Findings: Between November 29, 2021, and June 6, 2022,82 patients were screened; 53 were randomized to group A (n n =18), B (n n =17), and C (n n =18). With 14.3 months of median follow-up, IRRC-assessed median PFS was prolonged with the addition of HLX22 (A vs. . C, 15.1 vs. . 8.2 months, hazard ratio [HR] 0.5 [95% confidence interval (CI) 0.17-1.27]; B vs. . C, not reached vs. . 8.2 months, HR 0.1 [95% CI 0.04-0.52]). Confirmed ORR was comparable among groups (A vs. . B vs. . C, 77.8% vs. . 82.4% vs. . 88.9%). Treatment-related adverse events (TRAEs) were observed in 18 (100%), 16 (94.1%), and 17 (94.4%) patients, respectively. One (5.6%) patient in group C reported a grade 5 TRAE. Conclusions: Adding HLX22 to HLX02 and XELOX prolonged PFS and enhanced antitumor response in the first-line treatment of HER2-positive gastric cancer, with manageable safety. Funding: Shanghai Henlius Biotech, Inc.