The Phase I/II eNRGy trial: Zenocutuzumab in patients with cancers harboring NRG1 gene fusions

Abstract

Neuregulin 1 (NRG1) fusions are oncogenic drivers that have been detected in non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC), and other solid tumors. NRG1 fusions are rare, occurring in less than 1% of solid tumors. Patients with NRG1 fusion positive (NRG1+) cancer have limited therapeutic options. Zenocutuzumab is a novel, bispecific IgG1 antibody that targets both HER2 and HER3 proteins and inhibits NRG1 binding through a ‘Dock & Block^®‘ mechanism of action. Here, we describe the rationale and design of the Phase II component of the eNRGy trial, part of the overall open-label Phase I/II, multicenter trial exploring the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity of zenocutuzumab in patients with NRG1+ NSCLC, PDAC, or other solid tumors.