JCO Study Supports FDA Approval of BIZENGRI in NRG1+ Cholangiocarcinoma

Partner Therapeutics (PTx) has reported publication of results from the cholangiocarcinoma cohort of the Phase 2 eNRGy trial (NCT02912949) in the Journal of Clinical Oncology. The findings provided key clinical evidence supporting the recent U.S. Food and Drug Administration approval of BIZENGRI® (zenocutuzumab-zbco) for adults with advanced unresectable or metastatic cholangiocarcinoma harboring an NRG1 gene fusion whose disease has progressed after prior systemic therapy. The application was reviewed through the FDA’s Commissioner’s National Priority Voucher (CNPV) program, reflecting the significant unmet need in this rare cancer.

Targeting a Rare Driver in Cholangiocarcinoma

Cholangiocarcinoma is an aggressive cancer of the bile ducts with a five-year overall survival below 15%. Although NRG1 gene fusions occur in fewer than 1% of cases, they represent actionable oncogenic drivers in patients who often lack other targetable alterations. Standard second-line chemotherapy, including FOLFOX, produces limited response rates and is frequently associated with substantial toxicity.

Zenocutuzumab is a bispecific antibody that blocks HER2/HER3 dimerization and prevents NRG1 fusion proteins from activating HER3 signaling, thereby suppressing tumor growth. Because NRG1 fusions are rare and difficult to detect, comprehensive molecular profiling using both DNA- and RNA-based next-generation sequencing (NGS) is considered critical for identifying eligible patients.

eNRGy Trial Demonstrated Durable Clinical Benefit

The multicenter, open-label Phase 2 eNRGy trial evaluated zenocutuzumab in adults with advanced solid tumors harboring NRG1 gene fusions. The published cholangiocarcinoma analysis included 22 patients with unresectable or metastatic disease, of whom 19 were evaluable for efficacy. Most participants had received prior treatment, with a median of one previous systemic therapy and up to six prior treatment lines.

The investigator-assessed overall response rate (ORR) was 36.8%, while the median duration of response reached 7.4 months. Median progression-free survival (PFS) was 9.2 months, and the clinical benefit rate was 57.9%, reflecting patients who achieved complete or partial responses or maintained stable disease for more than six months.

The study also demonstrated the value of RNA-based testing. Tissue RNA sequencing identified 100% of NRG1 fusions, whereas DNA-based testing detected only 29%, emphasizing the importance of RNA profiling when evaluating patients for targeted therapy.

Favorable Safety Profile Supported Treatment

Zenocutuzumab was generally well tolerated across the study population. Most treatment-related adverse events were Grade 1 or 2, with diarrhea (27.3%), fatigue (18.2%), and nausea (13.6%) reported most frequently. No patients discontinued treatment because of treatment-related adverse events.

Commenting on the publication, Fiona Garner, Executive Director of Clinical Development at Partner Therapeutics, said the FDA approval and Journal of Clinical Oncology publication reinforce the clinical relevance of the eNRGy trial and the potential of zenocutuzumab to address a longstanding unmet need in patients with NRG1 fusion-positive cholangiocarcinoma.

Senior author James M. Cleary, MD, PhD, Director of Clinical Research in the Division of Gastrointestinal Oncology at Dana-Farber Cancer Institute, noted that the results demonstrate meaningful and durable antitumor activity with favorable tolerability while underscoring the importance of comprehensive molecular testing, particularly tissue-based RNA sequencing, to identify patients who may benefit from targeted therapy.

Expanding Use Across NRG1 Fusion-Positive Tumors

BIZENGRI first received accelerated FDA approval in 2024 for NRG1 fusion-positive non-small cell lung cancer and pancreatic adenocarcinoma following prior systemic therapy. The May 2026 approval expanded its indication to include advanced unresectable or metastatic cholangiocarcinoma, making it available across three NRG1 fusion-positive solid tumor types. The therapy is also incorporated into NCCN Clinical Practice Guidelines for non-small cell lung cancer, pancreatic adenocarcinoma, and cholangiocarcinoma, further supporting its role in precision oncology.

Reference

Partner Therapeutics Announces Publication of Results From the eNRGy Trial of Zenocutuzumab in Patients with NRG1+ Cholangiocarcinoma in Journal of Clinical Oncology (JCO) – Partner Therapeutics