Partner Therapeutics has announced that the US Food and Drug Administration (FDA) has approved BIZENGRI (zenocutuzumab-zbco) for the treatment of adults with advanced, unresectable or metastatic cholangiocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy. This marks the first targeted therapy approved specifically for NRG1+ cholangiocarcinoma, a molecularly defined cancer with a profound unmet need. The approval was expedited by PTx's receipt of a Commissioner's National Priority Voucher (CNPV).

BIZENGRI previously received Breakthrough Therapy Designation and Orphan Drug Designation (ODD) from the FDA for NRG1+ cholangiocarcinoma, reflecting the unmet need in this patient population.

Pritesh J. Gandhi, Chief Development Officer, Partner Therapeutics, said, "Today's FDA approval of BIZENGRI for NRG1 fusion-positive cholangiocarcinoma is a historic milestone for patients who have had no approved targeted therapy. We thank the patients, their families, and the investigators for their participation in the eNRGy trial. The results demonstrate meaningful tumor responses, durable benefit, and a favorable tolerability profile—and we are grateful that the FDA's Commissioner's National Priority Voucher pilot program greatly reduced the review time, helping bring this treatment to patients more quickly. We look forward to working with the oncology community to ensure appropriate patients can access BIZENGRI without delay."

The FDA approved BIZENGRI based on safety and efficacy data from the eNRGy trial, a multicenter, open-label, multi-cohort phase 2 clinical trial in adults with advanced solid tumors harboring NRG1 gene fusions. A total of 22 patients with unresectable or metastatic NRG1 fusion-positive cholangiocarcinoma were enrolled, with 19 evaluable for efficacy.

The major efficacy outcome measures were confirmed Overall Response Rate (ORR), which is the percentage of patients in a clinical trial whose cancer shrinks or disappears after treatment, and Duration of Response (DOR). The ORR was 36.8 percent with a DOR range of 2.8 to 12.9 months.

The most common adverse reactions (≥20 percent), excluding laboratory findings, were fatigue, diarrhea, musculoskeletal pain, abdominal pain, nausea, cough, dyspnea, and decreased appetite.

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, said, "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 percent 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."

BIZENGRI was first approved under accelerated approval in 2024 in advanced, unresectable or metastatic Non-Small Cell Lung Cancer (NSCLC) and pancreatic adenocarcinoma for patients harboring an NRG1 gene fusion on or after systemic therapy. Additionally, zenocutuzumab is included in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) for NSCLC, pancreatic adenocarcinoma, and cholangiocarcinoma.