Izalontamab (SI-B001), a Novel EGFRxHER3 Bispecific Antibody in Patients with Locally Advanced or Metastatic Epithelial Tumor: Results from First-in-Human Phase I/Ib Study
Jinhui Xue, Yuxiang Ma, Yuanyuan Zhao, Yongsheng Wang, Wei Hong, Yan Huang, Yunpeng Yang, Wenfeng Fang, Shaodong Hong, Yang Zhang, Qianwen Liu, Yi Zhu, Hai Zhu, Sa Xiao, Li Zhang, Hongyun Zhao
Abstract
PURPOSE: Izalontamab (SI-B001) is a novel EGFR×HER3 bispecific antibody. This first-in-human phase I study presents the safety and pharmacokinetics of izalontamab. PATIENTS AND METHODS: Previously treated patients with locally advanced or metastatic epithelial tumors were enrolled in the dose-escalation or dose-expansion phases. The dose-escalation phase consisted of an accelerated titration and a "3 + 3" design with nine dose levels from 0.4 to 28.0 mg/kg. The dose-expansion phase included five dose levels from 6.0 to 21.0 mg/kg. Izalontamab was administered intravenously weekly or every 2 weeks in a 4-week cycle. Available pretreatment specimens were obtained to explore the relationship between EGFR/HER3 expression and efficacy. RESULTS: Sixty patients were enrolled. Among the 60 enrolled patients, 49 had non-small cell lung cancer (NSCLC), 6 had nasopharyngeal cancer, 3 had head and neck cancer squamous cell carcinoma, and 2 had other types of cancer. The most common treatment-related adverse events were rash (42%), paronychia (25%), and infusion-related reactions (23%). No drug-related death occurred. Izalontamab displayed a nonlinear pharmacokinetic behavior, and clearance at steady state seemed to be approaching a dose-independent value at 6 mg/kg and above. The best response included two confirmed partial responses in patients with NSCLC and head and neck cancer squamous cell carcinoma; 18 patients had stable disease, including NSCLC (n = 17) and colorectal cancer (n = 1). The recommended phase II dose for izalontamab was determined as 9 to 16 mg/kg weekly. CONCLUSIONS: Izalontamab was well tolerated and demonstrated preliminary antitumor activity in patients with locally advanced or metastatic epithelial tumors, supporting it as a promising therapeutic candidate for combination therapies, with a phase III study currently underway.