FDA Approves Zenocutuzumab for NRG1 Fusion-Positive Cholangiocarcinoma

US-based Partner Therapeutics, a private, fully integrated biotechnology company, announced that FDA has approved zenocutuzumab-zbco (Bizengri) for adults with advanced unresectable or metastatic cholangiocarcinoma harboring a neuregulin 1 (NRG1) gene fusion whose disease progressed on or after prior systemic therapy.¹

According to the company, the approval marks the first targeted therapy specifically approved for NRG1 fusion-positive cholangiocarcinoma, a rare molecular subset of bile duct cancer associated with limited treatment options and poor outcomes. The review was expedited through the FDA Commissioner’s National Priority Voucher pilot program.

Zenocutuzumab, a bispecific antibody (bsAb),² previously received breakthrough therapy designation and orphan drug designation from FDA for this indication. The bsAb was initially granted accelerated approval in 2024 for patients with NRG1 fusion-positive non-small cell lung cancer and pancreatic adenocarcinoma following systemic therapy.³

“Today’s FDA approval of [Bizengri] For NRG1 fusion-positive cholangiocarcinoma is a historic milestone for patients who have had no approved targeted therapy,” said Pritesh J. Gandhi, chief development officer, Partner Therapeutics, in a company press release.¹ “The results demonstrate meaningful tumor responses, durable benefit, and a favorable tolerability profile—and we are grateful that the FDA’s Commissioner’s National Priority Voucher pilot program greatly reduced the review time, helping bring this treatment to patients more quickly.”

What clinical data supported FDA’s approval decision?

The approval was based on data from a phase 2 trial (eNRGy), which was a multicenter, open-label, multi-cohort study evaluating zenocutuzumab in adults with advanced solid tumors harboring NRG1 gene fusions.

A total of 22 patients with unresectable or metastatic NRG1 fusion-positive cholangiocarcinoma were enrolled in the study, including 19 patients evaluable for efficacy. The primary efficacy endpoints included confirmed overall response rate (ORR) and duration of response (DOR).

According to the company, the ORR was 36.8%, with durations of response ranging from 2.8 months to 12.9 months. The most commonly reported adverse reactions occurring in at least 20% of patients included fatigue, diarrhea, musculoskeletal pain, abdominal pain, nausea, cough, dyspnea, and decreased appetite.¹

Why is molecular testing important in NRG1 fusion-positive cancers?

NRG1 fusions occur in fewer than 1% of cholangiocarcinoma cases and are considered rare oncogenic drivers. The company stated that these alterations are frequently identified in patients who are otherwise negative for more common driver mutations, limiting targeted treatment options.¹

Zenocutuzumab is designed to block HER2/HER3 dimerization and inhibit interactions between NRG1 fusion proteins and HER3 signaling pathways. The therapy is intended to suppress downstream signaling associated with tumor growth and proliferation.

“NRG1 fusion–positive cholangiocarcinoma represents a rare but clinically important subset of disease with limited therapeutic options and poor outcomes,” said James Cleary, MD, PhD, director of clinical research in the Division of Gastrointestinal Oncology at Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School, in the press release.¹ “These data further highlight the essential role of comprehensive molecular testing, particularly tissue-based RNA-based sequencing, to reliably detect gene fusions such as NRG1 and ensure patients are appropriately identified for targeted therapy.”

How does the approval expand zenocutuzumab’s oncology indications?

With the new approval, zenocutuzumab is now indicated for NRG1 fusion-positive non-small cell lung cancer, pancreatic adenocarcinoma, and cholangiocarcinoma in patients whose disease progressed following prior systemic treatment. The bsAb is also included in National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for all three tumor types, according to the company.

Under an agreement with Merus, a subsidiary of Genmab, Partner Therapeutics holds exclusive US rights to develop, manufacture, and commercialize zenocutuzumab for NRG1-positive cancers.

References

1. Partner Therapeutics. Partner Therapeutics announces FDA approval of BIZENGRI (Zenocutuzumab-zbco) for NRG1 fusion-positive cholangiocarcinoma following receipt of FDA Commissioner’s National Priority Voucher. Published May 11, 2026. Accessed May 11, 2026. https://www.partnertx.com/partner-therapeutics-announces-fda-approval-of-bizengri-zenocutuzumab-zbco-for-nrg1-fusion-positive-cholangiocarcinoma/
2. Partner Therapeutics. Zenocutuzumab (Zeno). Accessed May 11, 2026. https://www.partnertx.com/research/zenocutuzumab/about/
3. FDA. FDA grants accelerated approval to zenocutuzumab-zbco for non-small cell lung cancer and pancreatic adenocarcinoma. Updated Dec. 4, 2024. Accessed May 11, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zenocutuzumab-zbco-non-small-cell-lung-cancer-and-pancreatic