eNRGy: Making progress toward a future for NRG1 fusion-positive cancer

Area of Science:

• Oncology
• Molecular Diagnostics
• Genetics

Background:

• The NRG1 gene fusion is a rare driver mutation found in various solid tumors.
• Targeted therapies are emerging for cancers with specific molecular alterations.

Purpose of the Study:

• To evaluate the efficacy and safety of zenocutuzumab in patients with advanced solid tumors harboring NRG1 gene fusions.
• To explore the potential of zenocutuzumab as a pan-tumor therapy.

Main Methods:

• The eNRGy trial was a Phase I/II study.
• Patients with advanced solid tumors and confirmed NRG1 fusions were enrolled.
• Tumor types included non-small cell lung cancer and pancreatic cancer.
• RNA-based next-generation sequencing was used for molecular profiling.

Main Results:

• Zenocutuzumab demonstrated significant clinical activity across multiple tumor types with NRG1 fusions.
• Observed responses suggest a broad efficacy of zenocutuzumab beyond specific cancer histologies.
• Treatment was generally well-tolerated with low-grade adverse events.

Conclusions:

• NRG1 gene fusions represent a targetable vulnerability across a range of solid tumors.
• Zenocutuzumab shows potential as an agnostic therapy for NRG1 fusion-positive cancers.
• Widespread implementation of comprehensive genomic profiling, including gene fusion detection, is crucial for patient identification.