Efficacy and Tolerability of Zenocutuzumab in Advanced NRG1 Fusion-Positive Biliary Tract Cancer

Zenocutuzumab, a HER2xHER3 bispecific antibody, produced responses in 7 of 19 evaluable patients with advanced NRG1 fusion-positive cholangiocarcinoma — an overall response rate of 36.8% (95% CI 16.3-61.6) in the single-arm phase 2 eNRGy trial. Median duration of response was 7.4 months and median progression-free survival was 9.2 months (95% CI 3.9-11.1). Most treatment-related adverse events were grade 1-2, most commonly diarrhoea (27.3%), and no patient discontinued treatment because of them. These figures should be read with caution: 22 patients were enrolled, the trial was single-arm with no comparator, and NRG1 fusions are very rare in cholangiocarcinoma. No targeted therapy is currently approved for this indication.