Multicenter phase 2 study of the HER3 monoclonal antibody, seribantumab, for solid tumors with neuregulin-1 fusions

Neuregulin-1 (NRG1) fusions are rare but actionable oncogenic drivers in solid tumors. Seribantumab is a fully human anti-HER3 IgG2 monoclonal antibody. The multicenter phase 2 CRESTONE study evaluated intravenous seribantumab 3000 mg once every week for advanced solid tumors with NRG fusions. A total of 54 patients with nine different tumor types featuring 19 different NRG1 fusion partners were enrolled. For the 29 patients included in the primary efficacy analysis, the investigator-assessed objective response rate was 34.5% (95% CI 17.9-54.3) with a disease control rate of 79% (60-92). The median progression-free survival was 5.4 months (95% CI 3.9-10.8) and the median overall survival was 20.3 months (10.2-NR). Adverse events were mostly grade 1 or 2. The authors conclude that these results suggest activity of seribantumab in patients with advanced solid tumors harboring NRG1 fusions.