FDA Approves Bizengri for NRG1 Fusion-Positive Bile Duct Cancer

The Food and Drug Administration on May 8 approved zenocutuzumab-zbco (Bizengri, Partner Therapeutics) for adults with advanced, unresectable or metastatic cholangiocarcinoma, a cancer of the bile ducts, that carries a neuregulin 1 (NRG1) gene fusion and has progressed on or after prior systemic therapy, according to the agency's announcement. The FDA described NRG1 fusion-positive cholangiocarcinoma as an extremely rare, life-threatening malignancy.

The application was part of the FDA Commissioner's National Priority Voucher (CNPV) pilot program, which is designed to speed the review of products that address national priorities. The FDA said it approved the application more than five months ahead of its goal date. Partner Therapeutics had announced on May 6 that it had received the voucher for this use.

The eNRGy data

The approval rests on eNRGy (NCT02912949), a multicenter, open-label, multi-cohort trial in adults with advanced solid tumors, which the company describes as a Phase 2 study. The trial enrolled 22 patients with unresectable or metastatic NRG1 fusion-positive cholangiocarcinoma, of whom 19 could be evaluated for efficacy, the FDA said.

The confirmed overall response rate was 36.8% (95% confidence interval 16.3 to 61.6), and responses lasted from 2.8 to 12.9 months, as determined by a blinded independent central review. There was no comparison group. The cholangiocarcinoma cohort's results were presented at the AACR-NCI-EORTC meeting in October 2025, according to the company.

The prescribing information includes warnings and precautions for infusion-related reactions, hypersensitivity and anaphylactic reactions, interstitial lung disease or pneumonitis, left ventricular dysfunction and embryo-fetal toxicity, the FDA said. The most common adverse reactions included diarrhea, musculoskeletal pain, fatigue, nausea and infusion-related reactions. The recommended dose is 750 mg by intravenous infusion every two weeks.

The drug and the disease

Zenocutuzumab-zbco is a bispecific antibody that blocks HER2/HER3 dimerization and the interaction of NRG1 fusion proteins with HER3, according to Partner Therapeutics. Bizengri was already approved, under accelerated approval, for NRG1 fusion-positive non-small cell lung cancer and pancreatic adenocarcinoma that progressed after prior systemic therapy.

The company says NRG1 fusions occur in fewer than 1% of cholangiocarcinoma cases. In its May 6 release, it described NRG1-positive cholangiocarcinoma as a cancer "for which no approved targeted therapy currently exists." The bile duct indication had also received breakthrough therapy designation, orphan drug designation and priority review, the FDA said.

"We are honored to receive this Commissioner's National Priority Voucher, which reflects the FDA's recognition of the profound unmet need facing patients with NRG1+ cholangiocarcinoma," Pritesh J. Gandhi, Partner Therapeutics' chief development officer, said in that release.

Bizengri is a registered trademark of Merus, a subsidiary of Genmab; Partner Therapeutics holds exclusive US rights to develop and sell the drug for NRG1-positive cancers under an agreement with Merus.