Results from the phase 2 eNRGy trial, published in the Journal of Clinical Oncology, supported the FDA approval of Zenocutuzumab as a second-line treatment for patients with advanced NRG1-positive Cholangiocarcinoma.
The study included 22 patients whose cancer had progressed after previous treatment. Zenocutuzumab achieved an objective response rate of 36.8%, compared with about 5% historically seen with standard second-line chemotherapy. The clinical benefit rate was 57.9%, and the median progression-free survival reached 9.2 months, more than double the roughly 4 months typically seen with chemotherapy.
The treatment was generally well tolerated. Most side effects, including diarrhea and infusion reactions, were mild and manageable.
NRG1 gene fusions occur in less than 1% of cholangiocarcinoma cases but can drive tumor growth. Zenocutuzumab is a bispecific antibody that targets HER2 and HER3 to block this signaling pathway. Researchers also emphasized that RNA-based next-generation sequencing is important for detecting NRG1 fusions, as standard DNA testing may miss these rare genetic changes.