Zenocutuzumab Demonstrates Durable Efficacy for Patients With NRG1-Positive Cholangiocarcinoma
Key Clinical Takeaways
- Design/Population: The eNRGy trial is an ongoing, open-label, single-arm, phase 2 study evaluating zenocutuzumab in adults with previously treated or treatment-ineligible, advanced NRG1 fusion–positive cancers. As of April 2025, 22 patients with NRG1+ cholangiocarcinoma were enrolled, with a median age of 57 years and most having received at least 1 prior systemic therapy.
- Key Outcomes: Among 19 efficacy-evaluable patients, zenocutuzumab achieved an objective response rate of 37%, with a median duration of response of 7.4 months and median progression-free survival of 9.2 months. Tumor markers showed consistent biochemical improvement, including CA 19-9 declines in all evaluable patients and GGT reductions in 84% of patients.
- Clinical Relevance: Zenocutuzumab demonstrated meaningful and durable antitumor activity with a favorable safety profile, with most adverse events limited to grade 1 or 2 severity. These results support zenocutuzumab as a promising targeted therapy option for patients with advanced NRG1 fusion–positive cholangiocarcinoma, a population with significant unmet clinical need.
According to updated results from the ongoing, phase 2 eNRGy trial, zenocutuzumab demonstrated durable efficacy and safety among patients with NRG1-positive cholangiocarcinoma.
These findings were presented by Alison Schram, MD, Memorial Sloan Kettering Cancer Center, New York, New York, at the International Conference on Molecular Targets and Cancer Therapeutics in Boston, Massachusetts.
In this open-label study, 19 previously treated patients unable to undergo other therapies received 750 mg of zenocutuzumab once every 2 weeks until disease progression or unacceptable toxicity. The primary end point was investigator-assessed overall response rate (ORR). Key secondary end points included duration of response, progression-free survival (PFS), clinical benefit rate, and safety.
At analysis, the ORR was 37%. The median duration of response was 7.4 months, and the median time to response was 1.9 months. The median PFS was 9.2 months, and the clinical benefit rate was 58%. Biomarker analyses showed that CA 19-9 reductions occurred in all evaluable patients, with reductions greater than 50% observed in 69% of patients. Gamma-glutamyl transferase (GGT) reductions occurred in 84% of patients, including reductions greater than 50% in 74% of patients. The most frequently observed grade ≥3 adverse events occurring in at least 2 patients included anemia (14%), hypomagnesemia (9%), and increased GGT (9%).
“Zenocutuzumab demonstrated clinically meaningful and durable efficacy with a favorable safety profile in patients with advanced NRG1[-positive] cholangiocarcinoma, an aggressive disease with few treatment options.”
Source:
Schram A, Cleary JM, Arnold D, et al. Zenocutuzumab efficacy and safety in advanced NRG1+ cholangiocarcinoma: Analysis from the phase 2 eNRGy Trial. Presented at the 2025 International Conference on Molecular Targets and Cancer Therapeutics. October 22-26; Boston, Massachusetts. A102.
