FDA Approves BIZENGRI (Zenocutuzumab-zbco) for NRG1 Fusion-Positive Cholangiocarcinoma
The FDA approved BIZENGRI (zenocutuzumab-zbco) on May 8, 2026 for NRG1 fusion-positive cholangiocarcinoma that progressed on prior therapy - Partner Therapeutics' third U.S. indication for the first HER2/HER3 bispecific antibody.
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Key Takeaways
- The FDA approved BIZENGRI for NRG1+ cholangiocarcinoma on May 8, 2026 after progression on prior therapy.
- In the eNRGy cohort, the objective response rate was 36.8% among 19 evaluable patients, with responses lasting 2.8 to 12.9 months.
- The dosage is 750 mg intravenously every two weeks, carrying a boxed warning for embryo-fetal toxicity.
- NRG1 fusions appear in fewer than 1% of cholangiocarcinoma cases, making companion NGS testing central to eligibility.
What the FDA approved
On May 8, 2026, the FDA cleared zenocutuzumab-zbco for adults whose advanced, unresectable or metastatic cholangiocarcinoma harbors an NRG1 gene fusion and has progressed on or after prior systemic therapy, according to the agency's approval notice. The FDA described the disease as an extremely rare, life-threatening malignancy.
Partner Therapeutics said the clearance followed an FDA Commissioner's National Priority Voucher, per the company's approval announcement. It is the third BIZENGRI indication, adding to the lung and pancreatic cancers cleared in December 2024.
What did the eNRGy trial show in cholangiocarcinoma?
Efficacy came from the eNRGy study, a multicenter, open-label, multi-cohort trial listed as NCT02912949 on ClinicalTrials.gov. It enrolled 22 patients with NRG1 fusion-positive cholangiocarcinoma, of whom 19 were evaluable for response.
The confirmed objective response rate was 36.8% (95% CI: 16.3, 61.6), with duration of response spanning 2.8 to 12.9 months by blinded independent central review. Investigators also reported a median progression-free survival of 9.2 months and clinical benefit in 57.9% of patients in the eNRGy phase 2 results shared by Dana-Farber Cancer Institute.
| Indication | Evaluable patients | Objective response rate |
|---|---|---|
| Cholangiocarcinoma (2026) | 19 | 36.8% |
| Pancreatic adenocarcinoma (2024) | 30 | 40% |
| NSCLC (2024) | 64 | 33% |
How rare is NRG1 fusion-positive cholangiocarcinoma?
NRG1 gene fusions are rare oncogenic drivers found in fewer than 1% of cholangiocarcinoma cases. The subtype also skews young: about 25% of patients with NRG1-positive cholangiocarcinoma are under age 40, a pattern seen in NRG1-positive pancreatic cancer as well.
Because the fusion is hard to detect on DNA panels alone, RNA-based next-generation sequencing matters. In the trial, all but one cholangiocarcinoma patient was confirmed using RNA testing, which shapes how oncologists should screen candidates.
How BIZENGRI works and how it is dosed
Zenocutuzumab-zbco is the first HER2/HER3-targeting bispecific antibody. It blocks the NRG1 fusion signal that drives tumor growth by docking onto HER2 and preventing HER3 activation.
The BIZENGRI prescribing information sets dosing at 750 mg by intravenous infusion every two weeks until disease progression or unacceptable toxicity, with tumor scans every eight weeks.
Safety profile and boxed warning
BIZENGRI carries a boxed warning for embryo-fetal toxicity. The label also warns of infusion-related reactions, hypersensitivity and anaphylaxis, interstitial lung disease or pneumonitis, and left ventricular dysfunction, as Merus detailed in its 2024 approval release.
These are managed rather than absolute barriers, but they require monitoring during infusion and across treatment. Prescribers should weigh cardiac and pulmonary history when selecting patients.
What the approval means for Partner Therapeutics
Partner Therapeutics is a private, integrated biotechnology company focused on hematology and oncology, with a portfolio that also includes sargramostim (LEUKINE). It holds exclusive U.S. rights to commercialize zenocutuzumab under a license from Merus, now part of Genmab.
Under that deal, Merus is eligible for up to $130 million in commercialization milestones plus tiered royalties from high single digits to the low twenties, according to an SEC filing. A third indication widens the addressable population that could trigger those payments.
Frequently Asked Questions
How effective was BIZENGRI in the eNRGy cholangiocarcinoma cohort?
Among 19 evaluable patients, the confirmed objective response rate was 36.8% (95% CI: 16.3, 61.6) and the duration of response ranged from 2.8 to 12.9 months, per the FDA.
How is BIZENGRI dosed for cholangiocarcinoma?
The label sets BIZENGRI at 750 mg by intravenous infusion every two weeks until disease progression or unacceptable toxicity, with tumor assessments every eight weeks.
Which patients with cholangiocarcinoma are eligible for BIZENGRI?
Adults with advanced, unresectable or metastatic cholangiocarcinoma that carries an NRG1 gene fusion and has progressed on or after prior systemic therapy.
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