FDA Approves Zenocutuzumab for NRG1 Fusion–Positive Cholangiocarcinoma

The FDA has approved zenocutuzumab-zbco (Bizengri) for adults with advanced unresectable or metastatic cholangiocarcinoma harboring an NRG1 gene fusion.¹ 

The approval is supported by efficacy and safety data from the cholangiocarcinoma cohort of the phase 2 eNRGy trial (NCT02912949), an open-label, registrational, multicenter study evaluating zenocutuzumab across multiple solid tumor types harboring NRG1 fusions. In the cholangiocarcinoma cohort, zenocutuzumab demonstrated an overall response rate (ORR) of 36.8% (95% CI, 16.3%-61.6%). The duration of response ranged from 2.8 to 12.9 months. Of note, no patients in this cohort discontinued therapy due to adverse events.²

“NRG1 fusion–positive cholangiocarcinoma represents a rare but clinically important subset of disease with limited therapeutic options and poor outcomes. In the eNRGy study, zenocutuzumab demonstrated a clinically meaningful overall response rate, and the drug was well tolerated with a favorable safety profile. Less than 1% of patients discontinued treatment due to a drug related adverse event, supporting its role as a targeted treatment option in this setting. 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,” James Cleary, MD, PhD, director of clinical research, Division of Gastrointestinal Oncology at Dana-Farber Cancer Institute and Associate Professor of Medicine at Harvard Medical School, stated in a news release.³

The overall safety profile of zenocutuzumab across the eNRGy trial was characterized by predominantly grade 1 or 2 adverse events.² Infusion-related reactions (IRRs) occurred in 13% of patients across the trial, with 91% arising during the first infusion; all were grade 1 or 2. Grade 2 interstitial lung disease/pneumonitis occurred in 0.6% of patients, resulting in permanent discontinuation.^2,3 Clinicians should assess left ventricular ejection fraction (LVEF) at baseline and monitor periodically during treatment, as grade 2 LVEF decreases were observed in 2% of evaluable patients.^2,4 

According to the FDA, the approval is the seventh approval under the Commissioner’s National Priority Voucher (CNPV) pilot program.

“Patients with this ultra-rare type of cancer desperately need new treatment options,” FDA Commissioner Marty Makary, MD, MPH, stated in a new release.¹ “Through the national priority voucher pilot program, the FDA is accelerating therapies for rare diseases with unmet medical needs, reviewing applications in significantly shortened timelines.

Overall, the eNRGy trial is a multicenter, open-label, dose-escalation and -expansion trial designed to assess the safety, tolerability, immunogenicity, and antitumor activity of zenocutuzumab in patients with solid tumors harboring an NRG1 fusion.⁵ The trial’s primary end point is ORR; secondary end points include duration of response, clinical benefit rate, progression-free survival, and safety.

In December 2024, zenocutuzumab received accelerated approval from the FDA in advanced NRG1+ pancreatic cancer and non–small cell lung cancer after receiving priority review and fast track designation; it also held a breakthrough therapy designation in pancreatic cancer. It is specifically indicated for treatment of adults with unresectable or metastatic disease that has progressed on or after prior systemic therapy.

And most recently before the approval, the FDA granted the agent breakthrough therapy designation for advanced unresectable or metastatic NRG1+ CCA in October 2025.

Zenocutuzumab is a bispecific antibody that blocks both HER2/HER3 dimerization and the interaction of NRG1 fusion proteins with HER3. NRG1 fusions function differently from more familiar oncogenic fusion drivers such as NTRK, RET, ROS1, ALK, and FGFR.² Rather than generating chimeric receptors, NRG1 fusions produce chimeric ligands that bind to HER3, triggering HER2/HER3 heterodimerization and downstream proliferative signaling. Standard DNA-based next-generation sequencing panels may miss these alterations; tissue-based RNA sequencing is required for reliable detection.²

References

1. US Food and Drug Administration. FDA grants seventh approval under the National Priority Voucher Pilot Program. FDA News Release. Published May 8, 2026. Accessed May 8, 2026. https://www.fda.gov/news-events/press-announcements/fda-grants-seventh-approval-under-national-priority-voucher-pilot-program

2. Partner Therapeutics, Inc. Partner Therapeutics announces submission of supplemental Biologics License Application (sBLA) to FDA for BIZENGRI® (zenocutuzumab-zbco) in NRG1 fusion positive cholangiocarcinoma. Press release. April 14, 2026. https://tinyurl.com/3yw2pk2a

3. Partner Therapeutics. Partner Therapeutics announces FDA approval of Bizengri (zenocutuzumab-zbco) for NRG1 fusion-positive cholangiocarcinoma. Published December 4, 2025. Accessed May 12, 2026. https://www.partnertx.com/partner-therapeutics-announces-fda-approval-of-bizengri-zenocutuzumab-zbco-for-nrg1-fusion-positive-cholangiocarcinoma/

4. Schram AM, Goto K, Kim DW, et al. Efficacy of zenocutuzumab in NRG1 fusion–positive cancer. N Engl J Med. 2025;392:566-576.

5. A study of zenocutuzumab (MCLA-128) in patients with solid tumors harboring an NRG1 fusion (eNRGy). ClinicalTrials.gov. Updated April 29, 2025. Accessed January 20, 2026. https://clinicaltrials.gov/study/NCT02912949