Partner Therapeutics, Inc. has announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to zenocutuzumab‑zbco for the treatment of adults with advanced unresectable or metastatic cholangiocarcinoma. Zenocutuzumab-zbco is being developed in a subset of patients with cholangiocarcinoma harbouring a neuregulin 1 (NRG1) gene fusion.
Cholangiocarcinoma (CCA) is a rare, aggressive malignancy of the bile ducts, typically diagnosed at an advanced stage when curative options are limited. There are approximately 8,000 cases annually in the US, and the five-year survival rate for all stages remains below 15%, emphasising the need for new therapeutic approaches. NRG1 gene fusions result from structural DNA rearrangements and typically occur without other oncogenic alterations. Like other fusions, they are best detected with a combination of tissue-based RNA and DNA next generation sequencing.
Systemic first-line treatment regimens in cholangiocarcinoma yield modest clinical benefit, with overall response rates (ORRs) of 26% to 29% and median overall survival (OS) of 11.7 to 12.8 months. Second-line treatment with FOLFOX provides an ORR of 5%, progression free survival of 4 months, and median OS of 6.2 months. Zenocutuzumab-zbco has shown activity in patients with cholangiocarcinoma harbouring NRG1 gene fusion.
“Patients with cholangiocarcinoma face a particularly aggressive cancer with poor prognosis and limited treatment options. Receiving Orphan Drug Designation for zenocutuzumab in patients with CCA harbouring the NRG1 gene fusion is a significant regulatory milestone for Partner Therapeutics and highlights the urgent need for new and effective treatment options for patients with this disease,” said Juan W. Valle, chief medical officer of the Cholangiocarcinoma Foundation.
The FDA grants Orphan Drug Designation to investigational products designed to treat rare diseases or conditions affecting fewer than 200,000 people in the United States. Designation benefits may include up to seven years of market exclusivity upon approval, exemption from FDA user fees, eligibility for clinical‑trial tax credits, and closer collaboration with the Agency during development.
Zenocutuzumab‑zbco, marketed as BIZENGRI, received Breakthrough Therapy Designation from the FDA in October 2025 and was granted accelerated approval in December 2024 for adults with advanced unresectable or metastatic non‑small cell lung cancer and pancreatic ductal adenocarcinoma harbouring NRG1 gene fusions following prior therapy.