FDA Receives sBLA for Zenocutuzumab in Advanced NRG1+ Cholangiocarcinoma

The FDA has received a supplemental Biologics License Application (sBLA) for zenocutuzumab-zbco (Bizengri) for the treatment of patients with advanced unresectable or metastatic cholangiocarcinoma harboring an NRG1 gene fusion, according to a news release from the developer, Partner Therapeutics, Inc.¹

Additionally, the National Comprehensive Cancer Network (NCCN) has updated its Clinical Practice Guidelines in Oncology for Biliary Tract Cancers to include zenocutuzumab as a recommended treatment option for this rare patient population. It is now in the guidelines as a Category 2A subsequent-line therapy and as a Category 2B recommendation for front-line treatment of NRG1 fusion-positive cholangiocarcinoma.

This regulatory milestone follows the December 2024 accelerated approval of the bispecific antibody for the treatment of adults with advanced unresectable or metastatic NRG1 fusion–positive non–small cell lung cancer or pancreatic ductal adenocarcinoma who have progressed on or after systemic therapy.²

“This submission marks an important step in advancing [zenocutuzumab] for patients with NRG1 fusion positive cholangiocarcinoma, a population with limited treatment options, and historically poor outcomes. Cholangiocarcinoma remains a challenging and aggressive disease, and we believe these data support the potential of [zenocutuzumab] to address a critical unmet need for patients whose tumors are driven by NRG1 gene fusions,” said Pritesh J. Gandhi, chief development officer of Partner Therapeutics, in the press release.¹ “Tissue‑based RNA testing is essential to identify rare oncogenic fusions such as NRG1 and ensure patients with these actionable alterations are not overlooked.”

What efficacy results support the use of zenocutuzumab in NRG1+ cholangiocarcinoma?

Clinical data supporting the sBLA submission primarily come from the cholangiocarcinoma cohort of the phase 1/2 eNRGy trial (NCT02912949). Among evaluable patients with advanced NRG1-positive cholangiocarcinoma, the overall response rate (ORR) was 36.8% (95% CI, 16.3%-61.6%), with a median duration of response of 12.9 months, as assessed by blinded independent central review.

“Cholangiocarcinoma remains a devastating disease, particularly in the advanced setting. The identification of NRG1 gene fusions has highlighted an actionable biomarker, and the eNRGy study data suggest that targeted inhibition with zenocutuzumab may represent a meaningful treatment approach for these patients,” added James Cleary, MD, PhD, associate professor of medicine at Harvard Medical School, and institute physician and director of Clinical Research in the Division of Gastrointestinal Oncology at Dana-Farber Cancer Institute.¹

How was the phase 2 eNRGy trial for zenocutuzumab structured?

The global, open-label, multi-arm eNRGy study was designed to evaluate the safety and antitumor activity of zenocutuzumab across various solid tumor types characterized by NRG1 gene fusions.³ Eligible participants were required to have a locally-advanced unresectable or metastatic solid tumor malignancy with a documented NRG1 gene fusion, and have received prior standard therapy or for which no standard therapy was available. Molecular eligibility was determined through comprehensive profiling using either DNA- or RNA-based next-generation sequencing-based assays to identify the presence of an NRG1 fusion. Patients also needed to have at least 1 measurable lesion per RECIST v1.1 guidelines and an ECOG performance status of 0 to 2.

The treatment regimen consisted of zenocutuzumab administered at a dose of 750 mg via intravenous infusion once every 2 weeks. Treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent.

What safety findings have been reported for zenocutuzumab-zbco?

The safety profile of zenocutuzumab in the cholangiocarcinoma population was generally manageable and consistent with results observed in the broader eNRGy study population. The investigators noted that treatment was well tolerated, with no patients discontinuing therapy due to adverse effects.

The FDA previously granted orphan drug designation to zenocutuzumab in NRG1 fusion-positive cholangiocarcinoma in February 2026.⁴

References

1. Partner Therapeutics announces submission of supplemental Biologics License Application (sBLA) to FDA for Bizengri (zenocutuzumab-zbco) in NRG1 fusion-positive cholangiocarcinoma and inclusion in NCCN Guidelines. News release. Partner Therapeutics, Inc. April 14, 2026. Accessed April 15, 2026. https://tinyurl.com/mrx43hbj
2. FDA approves zenocutuzumab-zbco for non-small cell lung cancer and pancreatic adenocarcinoma. News release. FDA. December 4, 2024. Accessed April 15, 2026. https://shorturl.at/E3HBS
3. A study of zenocutuzumab (MCLA-128) in patients with solid tumors harboring an NRG1 fusion (eNRGy). ClinicalTrials.gov. Updated April 29, 2025. Accessed April 15, 2026. https://tinyurl.com/3wcnzehr
4. Zenocutuzumab‑zbco receives FDA orphan drug designation for treatment of cholangiocarcinoma. News release. Partner Therapeutics, Inc. February 5, 2026. Accessed April 15, 2026. https://tinyurl.com/ymstnwkw