A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion (eNRGy)

Overview

• Registrational phase 2 (NEJM 2025): 204 patients with 12 tumour types treated; among 158 evaluable, response 30 percent (median duration 11.1 months, 19 percent ongoing), including 29 percent in lung and 42 percent in pancreatic cancer; median progression-free survival 6.8 months; treatment-related diarrhoea 18 percent, fatigue 12 percent, nausea 11 percent, infusion reactions 14 percent, one discontinuation. FDA accelerated approval for NRG1 fusion-positive pancreatic adenocarcinoma and lung cancer 4 December 2024 (label cohort of 30 pancreatic patients); cholangiocarcinoma added 2026. One UK site (Sarah Cannon Research Institute, London).
• NRG1 fusions bind HER3 and drive heterodimerisation with HER2. In this registrational phase 2 study, 204 patients with advanced NRG1 fusion-positive cancer of any type received zenocutuzumab 750 mg intravenously every two weeks. Among 158 with measurable disease enrolled at least 24 weeks before the cutoff, response occurred in 30 percent (95 percent confidence interval 23 to 37), including 27 of 93 with non-small-cell lung cancer (29 percent, 20 to 39) and 15 of 36 with pancreatic cancer (42 percent, 25 to 59), across multiple fusion partners. Adverse events were mostly grade 1 or 2: diarrhoea 18 percent, fatigue 12 percent, nausea 11 percent, infusion-related reactions 14 percent, with one discontinuation (New England Journal of Medicine 2025). The FDA granted accelerated approval on 4 December 2024. There is no NICE appraisal.