Zenocutuzumab Earns FDA National Priority Voucher in Cholangiocarcinoma

The FDA has given a Commissioner’s National Priority Voucher (CNPV) pilot program voucher to zenocutuzumab-zbco (Bizengri) for the treatment of adult patients with advanced unresectable or metastatic NRG1 fusion-positive cholangiocarcinoma who progressed on or after prior systemic therapy, according to a press release from the developer, Partner Therapeutics.¹

Zenocutuzumab is a first-in-class bispecific antibody designed to inhibit both HER2 and HER3, effectively blocking the NRG1-mediated signaling that drives tumor growth in these rare malignancies. The CNPV program is designed to reduce review times for drugs from 10 to 12 months to 1 to 2 months.

“We are honored to receive this [CNPV], which reflects the FDA’s recognition of the profound unmet need facing patients with [NRG1 fusion–positive] cholangiocarcinoma, an ultra-rare cancer for which no approved targeted therapy currently exists,” stated Pritesh J. Gandhi, chief development officer at Partner Therapeutics, in the press release.¹ “Receiving this voucher highlights the urgent need for new treatment options in NRG1 fusion-positive cholangiocarcinoma.”

The clinical evidence supporting the regulatory progress of zenocutuzumab in cholangiocarcinoma is derived from the multicenter, open-label phase 1/2 eNRGy trial (NCT02912949).

What efficacy data support the use of zenocutuzumab in cholangiocarcinoma?

The clinical evidence supporting the regulatory progress of zenocutuzumab in cholangiocarcinoma is derived from the multicenter, open-label phase 1/2 eNRGy trial (NCT02912949). Results were most recently shared at the 2025 AACR-NCI-EORTC Meeting.² Among the evaluable cohort of 19 patients with advanced NRG1-positive cholangiocarcinoma, zenocutuzumab demonstrated an overall response rate (ORR) of 37% (95% CI, 16%-62%), which consisted entirely of partial responses, and a clinical benefit rate (CBR) of 58% (95% CI, 33%-80%). The median duration of response (DOR) was 7.4 months (range, 3.6-11.1), and the median time to response was 1.9 months (range, 1.2-5.5).

Additionally, the median progression-free survival (PFS) in this cohort was reported to be 9.2 months (95% CI, 3.9-11.4); the median overall survival was not estimable (NE; 95% CI, 16.1-NE), with a median follow-up of 15.2 months (range, 1.2-34.1).

“The FDA’s recognition through the [CNPV] program emphasizes the urgency of advancing therapies for this population. In the eNRGy study, zenocutuzumab demonstrated clinically meaningful activity, with objective responses in more than one-third of evaluable patients and a median [PFS] of over 9 months,” added Alison Schram, MD, principal investigator of the eNRGy trial and gynecologic medical oncologist at Memorial Sloan Kettering Cancer Center.¹ “These data also highlight the critical role of comprehensive molecular testing, particularly RNA-based comprehensive molecular profiling, in identifying patients who may benefit from emerging targeted approaches.”

What are the dosing and eligibility criteria for the eNRGy trial?

The eNRGy trial evaluated zenocutuzumab administered at 750 mg via 2-hour intravenous infusion every 2 weeks. Treatment continued until disease progression, unacceptable toxicity, or patient withdrawal.

Patients were eligible for enrollment if they were 18 years or older with advanced or metastatic solid tumors harboring an NRG1 gene fusion as determined by comprehensive molecular profiling using next-generation sequencing. All patients were required to have been previously treated with or were unable to receive standard therapy, as well as an ECOG performance status ranging from 0 to 2.

The primary end point of the trial was ORR per RECIST v1.1 per investigator assessment. Secondary end points included DOR, CBR, PFS, and safety.

How has the regulatory landscape for zenocutuzumab evolved?

The receipt of the National Priority Voucher follows several previously reported major regulatory milestones for zenocutuzumab. In December 2024, the FDA granted accelerated approval to the agent for the treatment of adults with advanced NRG1-positive non–small cell lung cancer and pancreatic ductal adenocarcinoma who had disease progression on or after systemic therapy.³ Subsequent milestones for the cholangiocarcinoma indication included a breakthrough therapy designation in October 2025 and an orphan drug designation in February 2026.^4,5 Most recently, in April 2026, the FDA accepted a supplemental biologics license application for zenocutuzumab in this patient population.⁶

What safety findings were observed in the cholangiocarcinoma cohort?

At least 1 treatment-emergent adverse events occurred in 95% of patients, with 59% of patients experiencing a treatment-related adverse event. Grade 3 or higher adverse events included anemia in 14% of patients, hypomagnesemia in 9%, and increased gamma-glutamyltransferase levels in 9%.

“For patients [with] cholangiocarcinoma, innovation and timely diagnosis can make a profound difference. The FDA’s recognition of this potential treatment underscores both the unmet need in this rare biomarker-defined population and the importance of expanding access to comprehensive biomarker testing so patients can be matched to the most appropriate therapies as early as possible,” said Stacie Lindsey, chief executive officer of the Cholangiocarcinoma Foundation.¹

References

1. Partner Therapeutics announces receipt of FDA Commissioner’s National Priority Voucher for BIZENGRI (zenocutuzumab-zbco) in NRG1 fusion-positive cholangiocarcinoma. News release. Partner Therapeutics Inc. May 6, 2026. Accessed May 6, 2026. https://tinyurl.com/dnp66tty
2. Schram AM, Cleary JM, Arnold D, et al. Zenocutuzumab efficacy and safety in advanced NRG1+ cholangiocarcinoma: analysis from the phase 2 eNRGy trial. Presented at the 2025 AACR-NCI-EORTC Meeting; October 22-26, 2025; Boston, MA.
3. FDA grants accelerated approval to zenocutuzumab-zbco for non-small cell lung cancer and pancreatic adenocarcinoma. FDA. December 4, 2024. Accessed May 6, 2026. https://shorturl.at/E3HBS
4. Zenocutuzumab-zbco granted FDA breakthrough therapy designation for NRG1+ cholangiocarcinoma; data highlighting potential of zenocutuzumab-zbco in NRG1+ cholangiocarcinoma to be presented at AACR-NCI-EORTC. News release. October 24, 2025. Accessed May 6, 2026. https://tinyurl.com/3f8883ys
5. Zenocutuzumab‑zbco receives FDA orphan drug designation for treatment of cholangiocarcinoma. News release. Partner Therapeutics Inc. February 5, 2026. Accessed February 9, 2026. https://tinyurl.com/ymstnwkw
6. Partner Therapeutics announces submission of supplemental biologics license application (sBLA) to FDA for Bizengri (zenocutuzumab-zbco) in NRG1 fusion positive cholangiocarcinoma and inclusion in updated NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). News release. Partner Therapeutics Inc. April 14, 2026. Accessed May 6, 2026. https://tinyurl.com/mrx43hbj