Partner Therapeutics has announced that the US 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 (CCA) harbouring neuregulin 1 (NRG1) gene fusions.

Cholangiocarcinoma is a rare and aggressive bile duct cancer, with approximately 8,000 new cases diagnosed annually in the United States. The five-year survival rate remains below 15 percent, underscoring the urgent need for innovative therapies. Current first-line systemic treatments offer limited benefit, with overall response rates of 26–29 per cent and median overall survival of 11.7 to 12.8 months. Second-line therapy options provide even lower response rates and survival outcomes.

Zenocutuzumab-zbco, marketed as Bizengri, is being developed specifically for patients whose tumours harbour NRG1 gene fusions rare oncogenic drivers caused by structural DNA rearrangements. These fusions produce chimeric ligands that bind to HER3, triggering HER2/HER3 dimerisation and activating cancer-promoting signalling pathways. Zenocutuzumab-zbco is a bispecific antibody designed to block HER2/HER3 dimerisation and inhibit NRG1 fusion-driven signalling, thereby suppressing tumour growth.

Juan W. Valle, MD, Chief Medical Officer of the Cholangiocarcinoma Foundation, described the designation as a significant regulatory milestone, highlighting the need for effective therapies in this difficult-to-treat cancer.

Orphan Drug Designation is granted to therapies intended for rare diseases affecting fewer than 200,000 people in the US. The designation provides potential benefits including up to seven years of market exclusivity upon approval, tax credits for clinical trials, waiver of FDA user fees and enhanced regulatory support.

Zenocutuzumab-zbco previously received Breakthrough Therapy Designation in October 2025 and accelerated approval in December 2024 for adults with advanced unresectable or metastatic Non-Small Cell Lung Cancer (NSCLC) and pancreatic ductal adenocarcinoma harbouring NRG1 gene fusions following prior therapy. These approvals were based on overall response rate and duration of response, with continued approval contingent upon confirmatory trials.

Comprehensive molecular testing, including both tissue-based DNA and RNA next-generation sequencing, remains essential to identify rare actionable gene fusions such as NRG1.