A supplemental Biologics License Application (sBLA) seeking the approval of zenocutuzumab-zbco (Bizengri) for the treatment of adult patients with advanced unresectable or metastatic cholangiocarcinoma harboring an NRG1 gene fusion has been submitted to the FDA.1 Additionally, the National Comprehensive Cancer Network (NCCN) has added the agent to its Clinical Practice Guidelines in Oncology for biliary tract cancers as a Category 2A–recommended subsequent‑line therapy and as a Category 2B- recommended frontline treatment of NRG1 fusion–positive cholangiocarcinoma.2
The sBLA and NCCN Guideline addition were based on data from the phase 1/2 eNRGy study (NCT02912949). Patients in the cholangiocarcinoma cohort of eNRGy experienced an overall response rate (ORR) of 36.8% (95% CI, 16.3%-61.6%) and a median duration of response (DOR) of 12.9 months per blinded independent central review (BICR). Zenocutuzumab was generally well tolerated, and no patients discontinued treatment due to adverse events (AEs).
“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,” Pritesh J. Gandhi, PharmD, the chief development officer of Partner Therapeutics, stated in a news release.1 “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. Tissue‑based RNA testing is essential to identify rare oncogenic fusions such as NRG1 and ensure patients with these actionable alterations are not overlooked.”
How was eNRGy designed?
eNRGy was an open-label, multicenter, international, dose-escalation study that enrolled adult patients with solid tumors harboring an NRG1 fusion.3 Patients were also required to have an ECOG performance status of 0 to 2, an estimated life expectancy of at least 12 weeks, recovered from major surgery or other complications to grade 2 or less at baseline, an absolute neutrophil count of up to 1.5 x 109/L without colony stimulating factor support for at least 7 days before screening, minimum platelet counts of 75 x 109/L without transfusion support for at least 7 days before screening, and hemoglobin levels of at least 8 g/dL or 5 mmol/L.
Zenocutuzumab in NRG1 Fusion–Positive Cholangiocarcinoma
- A sBLA seeking the approval of zenocutuzumab for the treatment of adult patients with advanced unresectable or metastatic cholangiocarcinoma harboring an NRG1 gene fusion has been submitted to the FDA.
- Zenocutuzumab was also added to the NCCN Guidelines for biliary tract cancers as a Category 2A subsequent‑line therapy and as a Category 2B frontline treatment of NRG1 fusion–positive cholangiocarcinoma.
- Patients in the cholangiocarcinoma cohort of eNRGy experienced an ORR of 36.8% (95% CI, 16.3%-61.6%) and a median DOR of 12.9 months per blinded independent central review.
In the part 2 basket portion of the study, patients received intravenous zenocutuzumab at 750 mg every 2 weeks.
The primary end points were ORR per investigator assessment and DOR per RECIST 1.1 criteria per investigator assessment. Secondary end points included ORR per BICR, clinical benefit rate, DOR per BICR, time to response per RECIST 1.1 criteria, safety and tolerability, overall survival, and pharmacokinetic measures.
“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” James Cleary, MD, PhD, director of clinical research in the Division of Gastrointestinal Oncology and an institute physician at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School, both in Boston, Massachusetts, added in the news release.1
References
- 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. April 14, 2026. Accessed April 15, 2026. https://www.partnertx.com/partner-therapeutics-announces-submission-of-supplemental-biologics-license-application-sbla-to-fda-for-bizengri-zenocutuzumab-zbco-in-nrg1-fusion-positive-cholangiocarcinoma-and-inclusion-i/
- NCCN. Clinical Practice Guidelines in Oncology. Biliary tract cancers, version 1.2026. March 10, 2026. Accessed April 15, 2026. https://www.nccn.org/professionals/physician_gls/pdf/btc.pdf
- 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://clinicaltrials.gov/study/NCT02912949
