The US FDA awarded Orphan Drug Designation to zenocutuzumab-zbco (Bizengri) for treating adults with advanced unresectable or metastatic cholangiocarcinoma harboring a NRG1 gene fusion.

Cholangiocarcinoma (CCA) is a rare, aggressive malignancy of the bile ducts with poor prognosis and limited treatment options. NRG1 fusions are rare in CCA (<1% prevalence) but represent a compelling oncogenic driver and therapeutic target. The NRG1 chimeric ligands bind to HER3, triggering HER2/HER3 heterodimerization and activating downstream signaling pathways that cause cancer cells to grow and proliferate.

Zenocutuzumab is a bispecific antibody (BsAb) that blocks HER2/HER3 dimerization and NRG1 fusion interactions with HER3, suppressing those pathways. Originally developed by The Netherlands-based Merus NV, Partner Therapeutics secured commercial rights in the US to the molecule via a December 2024 license deal. Merus secured accelerated US FDA approval for zenocutuzumab in December 2024, for NRG1+ pancreatic adenocarcinoma and non–small cell lung cancer (NSCLC).

Industry context

Recent years have seen significant advances in the molecular characterization of CCA, leading to the approval of several targeted therapies, particularly for genetically defined subgroups. Recent approvals have seen FGFR2 inhibitors (led by Incyte’s pemigatinib/Pemazyre) and IDH1 inhibitors (Servier’s ivosidenib/Tibsovo) added to the therapeutic landscape.

Zenocutuzumab was awarded the FDA’s Breakthrough Therapy Designation for NRG1+ cholangiocarcinoma in October 2025 after producing a 37% objective response rate and 58% clinical benefit rate in the eNRGy trial. The data from the eNRGy trial is expected to support the submission of a supplemental biologics license application (sBLA) to the FDA in 2026.