On May 8, 2026, the U.S. Food and Drug Administration (FDA) approved the HER2- and HER3–directed bispecific antibody, zenocutuzumab-zbco (Bizengri), for adults with advanced, unresectable or metastatic cholangiocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy. NRG1-fusion positive cholangiocarcinoma is an extremely rare, life-threatening malignancy.
This application is part of the FDA Commissioner’s National Priority Review Voucher pilot program, which is designed to accelerate the review of products with the potential to address key national priorities.
Safety and Efficacy
The safety and efficacy of zenocutuzumab-zbco were evaluated in eNRGy (NCT02912949), a multicenter, open-label, multicohort clinical trial in adults with advanced solid tumors. A total of 22 patients with unresectable or metastatic NRG1 fusion-positive cholangiocarcinoma were enrolled in the eNRGy trial with 19 evaluable for efficacy.
The major efficacy outcome measures were confirmed overall response rate (ORR) and duration of response (DOR) as determined by a blinded independent central review according to RECIST v1.1. ORR was 36.8% (95% CI: 16.3, 61.6) and the DOR ranged from 2.8 to 12.9 months.
The prescribing information includes warnings and precautions for infusion-related reactions, hypersensitivity, anaphylactic reactions, interstitial lung disease/pneumonitis, left ventricular dysfunction, and embryo-fetal toxicity. The most common adverse reactions of zenocutuzumab-zbco include diarrhea musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema.
Recommended Dosage
The recommended zenocutuzumab-zbco dose is 750 mg as an intravenous infusion every 2 weeks until disease progression or unacceptable toxicity.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the assessment. The FDA approved this application over 5 months ahead of the FDA goal date.
This application was granted priority review. Zenocutuzumab-zbco received breakthrough designation and orphan drug designation.
Full prescribing information for zenocutuzumab-zbco will be posted on Drugs@FDA.
