Partner Therapeutics, Inc. (PTx), a private biotechnology company headquartered in Lexington, Massachusetts, announced receipt of an FDA Commissioner’s National Priority Voucher (CNPV) for Bizengri (zenocutuzumab-zbco), a HER2×HER3-targeted bispecific antibody, for the treatment of adults with advanced, unresectable or metastatic NRG1 fusion-positive cholangiocarcinoma whose disease has progressed on or after prior systemic therapy. The voucher, drawn from the FDA’s CNPV pilot program announced in June 2025, is tied to a supplemental Biologics License Application (sBLA) PTx submitted for a cholangiocarcinoma indication based on data from the Phase II eNRGy trial.
The CNPV pilot compresses the standard FDA review window of 10–12 months to as little as 1–2 months through a multidisciplinary, tumor board-style process involving the primary review team and senior agency leadership. Bizengri had already received Breakthrough Therapy Designation and Orphan Drug Designation from the US FDA for NRG1 fusion-positive cholangiocarcinoma prior to this announcement.
The sBLA for cholangiocarcinoma represents an indication expansion for a molecule that received FDA accelerated approval on December 4, 2024, for two other NRG1 fusion-positive tumor types: advanced unresectable or metastatic non-small cell lung cancer (NSCLC) and advanced unresectable or metastatic pancreatic adenocarcinoma, both after prior systemic therapy. Those approvals were based on overall response rate (ORR) and duration of response, and remain subject to confirmatory trial requirements.
The clinical data underpinning the cholangiocarcinoma sBLA come from the NRG1 fusion-positive cholangiocarcinoma cohort of the Phase II eNRGy trial, presented at the AACR-NCI-EORTC International Conference in October 2025. In 22 evaluable patients with a data cutoff of April 2025, zenocutuzumab-zbco produced an ORR of 37%, a median progression-free survival (PFS) of 9.2 months, a median time to response of 1.9 months, and a median duration of response (DoR) of 7.4 months. No formal p-values were reported, consistent with the single-arm registrational basket design in which ORR against a pre-specified historical control threshold serves as the primary endpoint. The safety profile was characterized by predominantly Grade 1–2 adverse events.
Zenocutuzumab-zbco (formerly MCLA-128) acts by blocking HER2/HER3 heterodimerization and preventing NRG1 fusion-derived chimeric ligands from binding HER3. NRG1 fusions differ mechanistically from the more commonly described chimeric receptor fusions such as NTRK, RET, ROS1, ALK, and FGFR: rather than generating a constitutively active chimeric receptor, NRG1 fusions produce oncogenic chimeric ligands that bind HER3 and drive downstream proliferative signaling through the HER2/HER3 dimer. Zenocutuzumab-zbco intercepts this pathway at the receptor level, a mechanism distinct from HER2-directed monoclonal antibodies such as Herceptin (trastuzumab) or small-molecule kinase inhibitors that target the intracellular domain.