The phase I/II eNRGy trial: Zenocutuzumab in patients with cancers harboring NRG1 gene fusions
Dong-Wan Kim1, Alison M Schram2, Antoine Hollebecque3
1Department of Internal Medicine, Seoul National University College of Medicine & Seoul National University Hospital, Seoul, 03080, Republic of Korea.
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.
Insights
Neuregulin 1 (NRG1) fusions drive rare cancers, offering limited treatment options. The eNRGy trial investigates zenocutuzumab, a bispecific antibody targeting HER2/HER3, for patients with NRG1 fusion-positive solid tumors.
Area of Science:
- Oncology
- Molecular Biology
- Drug Development
Background:
- Neuregulin 1 (NRG1) fusions are identified as oncogenic drivers in various solid tumors, including non-small-cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC).
- NRG1 fusions are rare, present in less than 1% of solid tumors, and patients diagnosed with NRG1 fusion-positive (NRG1+) cancer face limited therapeutic strategies.
- The 'Dock & Block®' mechanism of action employed by zenocutuzumab targets HER2 and HER3 proteins to inhibit NRG1 binding.
Purpose of the Study:
- To describe the rationale and design of the phase II component of the eNRGy trial.
- To explore the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity of zenocutuzumab.
- To evaluate zenocutuzumab in patients with NRG1+ NSCLC, PDAC, or other solid tumors.
Main Methods:
- Phase I/II, open-label, multicenter clinical trial.
- Administration of zenocutuzumab, a bispecific IgG1 antibody targeting HER2 and HER3.
- Evaluation of safety, tolerability, PK, PD, immunogenicity, and antitumor activity.
Main Results:
- The study is designed to assess the safety and efficacy of zenocutuzumab.
- Pharmacokinetic and pharmacodynamic profiles will be analyzed.
- Antitumor activity will be evaluated in patients with NRG1+ solid tumors.
Conclusions:
- Zenocutuzumab represents a novel therapeutic approach for NRG1 fusion-positive cancers.
- The eNRGy trial will provide critical data on the potential of zenocutuzumab in treating rare oncogenic-driven solid tumors.
- Further investigation is warranted to establish zenocutuzumab's role in the treatment landscape for NRG1+ NSCLC, PDAC, and other solid tumors.
