Dr Gershon on Deep Responses With Mirdametinib in NF1-PN

“We didn’t find that there was a particular patient that we could identify who was more likely to be a strong responder. Male or female, young or old—none of these obvious characteristics helped us define who would be a strong responder. The one trend that we did see least among adults was an association between longer time on therapy and the size of the response.”

Timothy Gershon, MD, PhD, professor, Department of Pediatrics, Emory University School of Medicine; director, the Children's Center for Neurosciences Research; member, the Cell and Molecular Biology Research Program, Winship Cancer Institute, Emory University, discusses results from an exploratory analysis of the phase 2b ReNeu (NCT03962543) evaluating patients with neurofibromatosis type 1–associated symptomatic inoperable plexiform neurofibroma (NF1-PN) who achieved deep responses with mirdametinib.

The current analysis consisted of patients who achieved deep responses, defined as an over 50% best reduction in target PN volume, regardless of objective response status, and was inclusive of those undergoing long-term follow-up. Exploratory assessments also compared baseline characteristics between patients achieving deep response and those with up to 50% volume reduction.

Results presented during the 2024 Society for Neuro-Oncology Annual Meeting indicated no specific baseline characteristics, including age, sex, or other demographics, were associated with a higher likelihood of achieving a deep response, Gershon reports. This suggests that mirdametinib is effective across a broad spectrum of patient populations, he explains. A trend was observed in which longer treatment duration appeared to correlate with deeper responses, although the causal relationship remains unclear, Gershon notes. It is possible that prolonged therapy contributed to greater tumor shrinkage, or conversely, that patients achieving larger responses remained on therapy longer. These findings highlight the importance of extended treatment in achieving optimal outcomes, he says.

Mirdametinib has previously demonstrated a manageable safety profile, deep responses, and the potential for enhancing health-related quality of life (QOL), according to prior data presented at the 2024 ASCO Annual Meeting. In August 2024, the agent was granted priority review status by the FDA, with a decision expected by February 28, 2025. These data further support the role of mirdametinib as a valuable therapy for patients with NF1-PN, particularly given its ability to generate meaningful and durable reductions in tumor volume alongside improvements in QOL metrics, Gershon concludes.