Zenocutuzumab: A Promising Therapy for NRG1 Fusion-Positive Cancers

Zenocutuzumab (MCLA-128), also known as Zeno, is a bispecific antibody designed to target HER2 and HER3 proteins. It is being developed as a treatment for cancers driven by NRG1 (neuregulin 1) gene rearrangements, which are oncogenic drivers in various solid tumors, including non-small cell lung cancer (NSCLC) and pancreatic cancer.

Mechanism of Action

Zenocutuzumab targets two distinct domains on the HER2 and HER3 proteins. By binding to these domains, it disrupts the signaling pathways that drive cancer cell proliferation and survival. This dual targeting approach enhances the antibody's ability to inhibit tumor growth effectively.

Clinical Efficacy

Clinical trials have demonstrated the efficacy of zenocutuzumab in treating NRG1 fusion-positive cancers. The trials showed an objective response rate (ORR) in patients with NSCLC and pancreatic cancer, indicating a significant improvement in disease control and patient outcomes.

Safety Profile

Zenocutuzumab has a manageable safety profile, with the most common adverse events being diarrhea, infusion-related reactions, and decreased ejection fraction. These side effects are generally manageable with appropriate supportive care.

Real-World Application

In real-world settings, zenocutuzumab has shown durable responses and prolonged overall survival in patients with NRG1 fusion-positive cancers. The therapy is being studied in various HER2-expressing solid tumors, with the goal of improving outcomes for patients with these difficult-to-treat cancers.

Conclusion

Zenocutuzumab represents a significant advancement in the treatment of NRG1 fusion-positive cancers, offering new hope to patients with advanced disease. As research continues, zenocutuzumab may be combined with other targeted therapies to further enhance its efficacy and improve patient outcomes.