On May 8, 2026, the Food and Drug Administration approved zenocutuzumab-zbco for adults with advanced, unresectable or metastatic cholangiocarcinoma harbouring 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 (CNPV) pilot program, which is designed to accelerate the review of products with the potential to address key national priorities.

Full prescribing information for zenocutuzumab-zbco will be posted on Drugs@FDA.

Safety and Efficacy

The safety and efficacy of zenocutuzumab-zbco were evaluated in eNRGy (NCT02912949), a multicenter, open-label, multi-cohort 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 (ILD)/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 (IRR), dyspnea, rash, constipation, vomiting, abdominal pain, and edema.

Recommended Dosage

The recommended zenocutuzumab-zbco dose is 750 mg as an intravenous infusion every two 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. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

Source: FDA