On May 8, 2026, the U.S. Food and Drug Administration (FDA) approved zenocutuzumab-zbco (Bizengri; Partner Therapeutics, Inc.) for adult patients with advanced, unresectable or metastatic cholangiocarcinoma harboring a neuregulin 1 (NRG1) gene fusion whose disease has progressed on or after prior systemic therapy. This approval addresses an extremely rare and life-threatening malignancy with limited prior treatment options and was granted more than five months ahead of the FDA goal date.

Clinical Takeaway

Zenocutuzumab-zbco becomes the first therapy specifically approved for NRG1 fusion-positive cholangiocarcinoma, offering oncology clinicians a targeted option for a molecularly defined patient population that has historically lacked dedicated systemic treatments following progression on prior therapy.

Drug Profile & Mechanism

  • Drug name: Zenocutuzumab-zbco (brand name: Bizengri)
  • Developer: Partner Therapeutics, Inc.
  • Drug class: Bispecific antibody targeting HER2 and HER3, designed to block NRG1 (neuregulin 1) from binding to HER3 and thereby inhibit downstream oncogenic signaling driven by NRG1 gene fusions
  • Administration: Intravenous (IV) infusion
  • Recommended dose: 750 mg IV every two weeks until disease progression or unacceptable toxicity

Target Population

  • Indication: Adult patients with advanced, unresectable or metastatic cholangiocarcinoma harboring an NRG1 gene fusion
  • Prior therapy requirement: Disease progression on or after prior systemic therapy
  • Biomarker requirement: Confirmed NRG1 gene fusion; molecular testing is required to identify eligible patients
  • Disease context: NRG1 fusion-positive cholangiocarcinoma is described by the FDA as an extremely rare, life-threatening malignancy

Study Design

  • Trial name: eNRGy (NCT02912949)
  • Design: Multicenter, open-label, multi-cohort clinical trial
  • Population: Adults with advanced solid tumors harboring NRG1 gene fusions
  • Cholangiocarcinoma cohort: 22 patients enrolled with unresectable or metastatic NRG1 fusion-positive cholangiocarcinoma; 19 patients were evaluable for efficacy
  • Response assessment: Conducted by blinded independent central review (BICR) per RECIST v1.1

Endpoints

  • Primary efficacy endpoints:
    • Confirmed overall response rate (ORR) by BICR per RECIST v1.1
    • Duration of response (DOR) by BICR per RECIST v1.1

Efficacy Outcomes

  • Overall Response Rate (ORR): 36.8% (95% CI: 16.3–61.6) among the 19 efficacy-evaluable patients
  • Duration of Response (DOR): Ranged from 2.8 to 12.9 months
  • All responses were confirmed per protocol requirements
  • These results supported approval in the context of a rare disease with a small evaluable population and no approved targeted alternatives

Safety

The prescribing information includes the following warnings and precautions:

  • Infusion-related reactions (IRR) / hypersensitivity / anaphylactic reactions
  • Interstitial lung disease (ILD) / pneumonitis
  • Left ventricular dysfunction
  • Embryo-fetal toxicity

The most common adverse reactions reported with zenocutuzumab-zbco include:

  • Diarrhea
  • Musculoskeletal pain
  • Fatigue
  • Nausea
  • Infusion-related reactions (IRR)
  • Dyspnea
  • Rash
  • Constipation
  • Vomiting
  • Abdominal pain
  • Edema

Healthcare professionals should report serious adverse events to the FDA MedWatch Reporting System at 1-800-FDA-1088.

Regulatory Context

  • Approval date: May 8, 2026
  • FDA expedited designations received:
    • Priority Review
    • Breakthrough Therapy Designation
    • Orphan Drug Designation
  • Application reviewed under the FDA Commissioner’s National Priority Review Voucher (CNPV) pilot program, designed to accelerate review of products addressing key national priorities
  • Approved more than 5 months ahead of the FDA goal date
  • The FDA’s voluntary Assessment Aid submission was used to facilitate the review process

Key Clinical Implications

✔ Molecular testing for NRG1 gene fusions is now clinically actionable in cholangiocarcinoma — clinicians should ensure comprehensive genomic profiling includes NRG1 fusion detection in patients with advanced biliary tract cancers.

✔ Zenocutuzumab-zbco is now the standard targeted option for NRG1 fusion-positive cholangiocarcinoma in patients who have progressed on at least one prior systemic therapy, filling a critical unmet need in this rare population.

✔ Monitor patients proactively for IRRs and cardiopulmonary toxicities, including infusion-related reactions, ILD/pneumonitis, and left ventricular dysfunction, given the warnings and precautions outlined in the prescribing information.

✔ Counsel patients of reproductive potential regarding embryo-fetal toxicity and the need for effective contraception during treatment, consistent with the prescribing information requirements.

✔ The eNRGy trial enrolled only 22 cholangiocarcinoma patients, reflecting the extreme rarity of this NRG1 fusion-positive subtype; clinicians should interpret efficacy data within the context of this small cohort while recognizing the meaningful ORR of 36.8% observed.

Bottom Line

The FDA approval of zenocutuzumab-zbco (Bizengri) represents a landmark advance for patients with NRG1 fusion-positive advanced cholangiocarcinoma — an ultra-rare molecular subtype with no prior approved targeted therapy. With an ORR of 36.8% and a manageable safety profile in the eNRGy trial, Bizengri provides oncologists with the first biomarker-driven treatment option in this setting. Routine comprehensive genomic profiling that includes NRG1 fusion detection should be considered standard of care to identify patients who may benefit from this therapy.

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