Dr Forsyth on Leptomeningeal Disease in HER2+ Breast Cancer and TNBC

Peter Forsyth, MD, chairman, Neuro-Oncology Program, Moffitt Cancer Center; professor, oncology, the University of South Florida, discusses the importance of evaluating leptomeningeal disease in a first-in-human phase 1 trial (NCT05809752) of dose-escalating intrathecal dendritic cells (cDC1s) targeting HER2/HER3 in patients with triple-negative breast cancer (TNBC) or HER2-positive breast cancer.

At the 2024 ASCO Annual Meeting, Forsyth and colleagues delved into the topic, presenting background on the first-in-human trial investigating dose escalating cDC1s primed against HER2/HER3 in leptomeningeal disease from triple-negative or HER2-positive breast cancer.

Leptomeningeal disease, though relatively uncommon, affects approximately 5% of patients, Forsyth begins. However, the incidence of this complication appears to be on the rise, Forsyth says. This increase is partly due to improvements in systemic treatments for cancer, which allow patients to live longer, giving more time for this condition to develop, he reports. Leptomeningeal disease is a significant concern because it is poorly understood, devastating, and rapidly fatal, making treatments for it a major unmet medical need, Forsyth explains. As breast cancer treatments continue to improve, the incidence of leptomeningeal disease may also increase, underscoring the urgency of addressing it now, he adds.

This study represents a significant milestone as it is the first of its kind—a first-in-human study of an immune cellular therapy administered intrathecally specifically for leptomeningeal disease, Forsyth expands. Due to its pioneering nature, the study is proceeding with caution to ensure safety and to determine the therapy’s effectiveness, Forsyth elucidates, noting that this careful approach is essential given the novelty and potential impact of the treatment.

Leptomeningeal disease is becoming more prevalent due to extended patient survival from improved cancer treatments, but it remains a critical and poorly understood medical issue, he continues. The innovative first-in-human study of intrathecal immune cellular therapy offers hope, but it requires meticulous progress to confirm both safety and efficacy, Forsyth concludes.