Zenocutuzumab Effective Against NRG1 Fusion Cancers

TOPLINE:

Zenocutuzumab demonstrates efficacy in patients with Neuregulin 1 (NRG1) fusion–positive cancer, achieving a 30% response rate across multiple tumor types. The bispecific antibody shows particularly promising results in non–small cell lung cancer (NSCLC) and pancreatic cancer patients, with responses lasting a median of 11.1 months.

METHODOLOGY:

• The US Food and Drug Administration (FDA) approved zenocutuzumab (Bizengri, Merus) for adults with NSCLC or pancreatic adenocarcinoma — specifically, for those with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma harboring a NRG1 gene fusion who progress on or after prior systemic therapy. The approval was based on earlier findings of this trial.
• The registrational, phase 2 clinical study enrolled 204 patients with 12 different types of advanced NRG1 fusion–positive cancer at 49 centers across 12 countries.
• Participants received zenocutuzumab at a dose of 750 mg intravenously every 2 weeks until disease progression, death, unacceptable toxicity, or withdrawal of consent.
• Primary endpoint assessment included overall response (complete or partial response) according to investigator assessment, while secondary endpoints encompassed duration of response, progression-free survival, and safety.
• Analysis focused on patients with documented NRG1 fusion identified through local testing or centralized prescreening using next-generation sequencing, who received at least one dose of zenocutuzumab at least 24 weeks before the data-cutoff date.

TAKEAWAY:

• Among 158 patients with measurable disease, the overall response rate was 30% (95% CI, 23-37), with a median duration of response of 11.1 months (95% CI, 7.4-12.9).
• In patients with NSCLC, the response rate was 29% (95% CI, 20-39), with a median duration of response of 12.7 months (95% CI, 7.4-20.4).
• Pancreatic cancer patients showed a response rate of 42% (95% CI, 25-59), with a median duration of response of 7.4 months (95% CI, 4.0-11.2).
• The median progression-free survival across all patients was 6.8 months (95% CI, 5.5-9.1), with adverse events primarily being grade 1 or 2.

IN PRACTICE:

“In this study, zenocutuzumab, a bispecific antibody against HER2 and HER3, showed antitumor activity in patients with advanced NRG1 fusion–positive cancer, notably NSCLC and pancreatic cancer. Responses were observed across multiple tumor types and fusion partners. This study validates NRG1 fusions as an actionable therapeutic target,” wrote the authors of the study.

SOURCE:

The study was led by Alison Schram, MD, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College in New York. It was published online on February 6 in The New England Journal of Medicine.

LIMITATIONS:

According to the authors, while efficacy was observed across multiple cancer types, patient enrollment was substantially higher for NSCLC and pancreatic cancer than other tumor types, potentially limiting the understanding of efficacy across different histological types. Additionally, the study population showed underrepresentation of Black participants (3%) compared with White (54%) and Asian (33%) participants.

DISCLOSURES:

The study was supported by Merus.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.