News|Articles|February 6, 2026

FDA Grants Orphan Drug Designation to Zenocutuzumab for Cholangiocarcinoma

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Key Takeaways

FDA orphan designation for zenocutuzumab‑zbco targets NRG1 fusion–positive advanced cholangiocarcinoma, a small molecular subset within an aggressive malignancy with <15% five-year survival.
Orphan designation provides development incentives including seven-year exclusivity post-approval, certain fee exemptions, clinical trial tax credits, and increased FDA engagement to address unmet need.
NRG1 fusions often occur without other canonical oncogenic drivers, necessitating broad genomic profiling; both DNA- and RNA-based NGS improves detection versus DNA-only approaches.
Zenocutuzumab‑zbco is a bispecific antibody that blocks NRG1 ligand–HER3 binding and downstream HER2/HER3 signaling, supporting a tumor-agnostic strategy across NRG1 fusion–positive cancers.
Ongoing eNRGy trial assessment emphasizes efficacy and safety surveillance, with key risks including infusion reactions, pneumonitis, cardiac dysfunction, and embryo-fetal toxicity.

The FDA has granted orphan drug designation to zenocutuzumab-zbco for the treatment of adults with advanced unresectable or metastatic cholangiocarcinoma.

The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to zenocutuzumab-zbco for the treatment of adults with advanced unresectable or metastatic cholangiocarcinoma, according to an announcement from Partner Therapeutics. The designation applies specifically to patients whose tumors harbor a neuregulin 1 (NRG1) gene fusion, a rare but actionable genetic alteration.

"Patients with cholangiocarcinoma face a particularly aggressive cancer with poor prognosis and limited treatment options. Receiving orphan drug designation for zenocutuzumab in patients with CCA harboring the NRG1 gene fusion is a significant regulatory milestone for Partner Therapeutics and highlights the urgent need for new and effective treatment options for patients with this disease" said Dr. Juan W. Valle, chief medical officer of the Cholangiocarcinoma Foundation.

Cholangiocarcinoma, also known as bile duct cancer, is an aggressive and uncommon disease that is often diagnosed at an advanced stage. Treatment options are limited, and outcomes remain poor for many patients. The FDA designation represents an important regulatory milestone that may help accelerate development of zenocutuzumab-zbco.

FDA orphan drug designation advances targeted therapy for cholangiocarcinoma

Orphan drug designation is granted to therapies intended to treat rare diseases affecting fewer than 200,000 people in the United States. The designation is designed to encourage development of treatments for conditions with significant unmet medical need. Benefits can include up to seven years of market exclusivity following approval, exemption from certain FDA fees, eligibility for tax credits related to clinical trial costs, and increased collaboration with the FDA during the development process.

Zenocutuzumab-zbco has already received breakthrough therapy designation and accelerated approval for other cancers driven by NRG1 gene fusions, including non-small cell lung cancer and pancreatic ductal adenocarcinoma. The new designation expands its potential role in rare gastrointestinal cancers.

Why NRG1 gene fusions matter in bile duct cancer

Cholangiocarcinoma affects approximately 8,000 people each year in the United States, and the five-year survival rate across all stages remains below 15 percent. Many patients are diagnosed when surgery is no longer an option, making systemic therapy the mainstay of treatment.

NRG1 gene fusions occur when segments of DNA rearrange and form abnormal signaling molecules that drive cancer growth. Unlike more common cancer drivers, NRG1 fusions typically appear without other oncogenic alterations. Because of their rarity, these fusions may be missed unless comprehensive molecular testing is performed.

Experts emphasize that identifying NRG1 gene fusions requires both DNA- and RNA-based next-generation sequencing. For patients who test positive, targeted therapies such as zenocutuzumab-zbco may offer a more personalized treatment approach.

How zenocutuzumab-zbco works

Zenocutuzumab-zbco is a bispecific antibody designed to block abnormal signaling caused by NRG1 gene fusions. These fusions activate cancer growth by binding to HER3 and triggering HER2/HER3 signaling pathways. Zenocutuzumab-zbco prevents this interaction, which may slow or stop tumor growth.

In clinical studies, zenocutuzumab-zbco demonstrated activity across multiple tumor types harboring NRG1 gene fusions, supporting its tumor-agnostic development strategy.

Additional findings and what comes next

Zenocutuzumab-zbco continues to be studied in the ongoing eNRGy clinical trial, which is evaluating its safety and effectiveness in patients with NRG1 fusion–positive cancers. Safety monitoring remains an important focus, with known risks including infusion-related reactions, lung inflammation, heart dysfunction, and embryo-fetal toxicity.

For patients and caregivers, the FDA’s orphan drug designation offers cautious optimism that new, targeted options may become available for a disease with few effective treatments.

As research continues, experts stress that patients with advanced cholangiocarcinoma should discuss comprehensive genomic testing and clinical trial opportunities with their care teams.

References

“Zenocutuzumab‑zbco Receives FDA Orphan Drug Designation for Treatment of Cholangiocarcinoma,” by Partner Therapeutics, Inc. News release; Feb. 6, 2026.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI and reviewed by a human editor.

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