Dr Bekaii-Saab on the FDA Approval of Zenocutuzumab in NRG1+ Cholangiocarcinoma

"This is one more actionable target with an approval based on a good response rate... when it works, it works extremely well, so I'm excited about this approval."

Tanios S. Bekaii-Saab, MD, FACP, the David F. and Margaret T. Grohne Professor of Novel Therapeutics for Cancer Research I at Mayo Clinic College of Medicine and Science; the division chair of Hematology/Medical Oncology at Mayo Clinic; the co-leader of the Advanced Clinical and Translational Science Program; and the disease group leader for Gastrointestinal Cancers for the Mayo Clinic Comprehensive Cancer Center, discussed the clinical impact of the FDA approval of zenocutuzumab-zbco (Bizengri) in NRG1 fusion–positive cholangiocarcinoma (CCA).

On May 8, 2026, the agent was approved for adult patients with NRG1 fusion–positive advanced, unresectable, or metastatic CCA who have progressed on or after prior systemic therapy. This regulatory milestone was supported by findings from the phase 1/2 eNRGy trial (NCT02912949), which demonstrated an overall response rate (ORR) of 36.8% (95% CI, 16.3%-61.6%) among 19 evaluable patients per blinded independent central review (BICR). The duration of response (DOR) in the study ranged from 2.8 months to 12.9 months per BICR.

Bekaii-Saab characterized the approval as a significant addition to the growing therapeutic landscape for biliary and pancreatic cancers. Although NRG1 fusions are more rare, the ability to achieve an ORR of nearly 37% is a major advancement compared to standard chemotherapy, which typically yields response rates of less than 5% in the pre-treated setting, Bekaii-Saab noted. With this approval, zenocutuzumab joins an expanding list of targeted therapies approved for CCA, including agents targeting FGFR and IDH1 such as pemigatinib (Pemazyre), futibatinib (Lytgobi), and ivosidenib (Tibsovo), he added.

Bekaii-Saab emphasized that with this approval, approximately 30% to 40% of patients with CCA now have an actionable target for treatment. Having worked with the antibody for several years in both the eNRGy study and the clinic, he described the agent as "extremely safe" and highly effective for patients harboring the specific fusion. Ultimately, he concluded that identifying these rare but actionable targets is essential for improving outcomes in a disease where precision medicine is increasingly becoming the standard of care.On May 8, 2026, the agent was approved for adult patients with NRG1 fusion–positive advanced, unresectable, or metastatic CCA who have progressed on or after prior systemic therapy. from the phase 1/2 eNRGy trial (NCT02912949), which demonstrated an overall response rate (ORR) of 36.8% (95% CI, 16.3%-61.6%) among 19 evaluable patients per blinded independent central review (BICR). The duration of response (DOR) in the study ranged from 2.8 months to 12.9 months per BICR.