The approval of Zenocutuzumab was based on the pivotal eNRGy trial (NCT02912949), which enrolled patients with advanced NRG1 fusion-positive solid tumors who had failed previous treatments. The treatment regimen was 750mg intravenous injection every two weeks. Among 79 NSCLC patients, 72% had received chemotherapy, and 11% had used afatinib . The main fusion partners were CD74 (34%) and SLC3A2 (28%). The treatment achieved an objective response rate (ORR) of 37.2% with a median duration of response (DOR) of 14.9 months. Tumor burden significantly decreased in 82% of patients, and 78% of pancreatic cancer patients showed over 50% reduction in CA19-9 levels. Among 33 pancreatic cancer patients , 42.4% achieved an objective response (including one complete response), with a median DOR of 9.1 months, and 72.7% achieved clinical benefit. Regarding safety , grade 3 or higher adverse events occurred in only 6% of patients, with no treatment-related discontinuations. The main adverse reactions were diarrhea (21%) and injection reactions (18%). These data demonstrate that Zenocutuzumab significantly extends response duration while breaking away from traditional targeted therapy's dependence on biomarkers, with its efficacy stemming from precise blockade of the HER2/HER3 signaling pathway .