Dr Forsyth on the Potential Utility of Intrathecal cDC1s in Leptomeningeal Disease

Peter Forsyth, MD, chairman, Neuro-Oncology Program, Moffitt Cancer Center; professor of oncology, the University of South Florida, discusses next steps for the investigation of dose-escalating intrathecal dendritic cells (cDC1s) targeting HER2/HER3 in patients with leptomeningeal disease.

At the 2024 ASCO Annual Meeting, Forsyth and colleagues presented information on a first-in-human phase 1 trial (NCT05809752) that is evaluating this intrathecally administered immune cellular therapy in patients with leptomeningeal disease from triple-negative breast cancer (TNBC) or HER2-positive breast cancer. This study is the first to explore an immune cellular therapy delivered intrathecally specifically for leptomeningeal disease, a condition characterized by the spread of cancer to the membranes surrounding the brain and spinal cord.

The trial focuses primarily on safety, which means that efficacy outcomes are not yet clear and will only be determined as a secondary end point, Forsyth clarifies. The optimal dosing still needs to be identified, and this will require further research with a larger cohort of patients, he adds. Given the rarity of leptomeningeal disease, expanding the study to include additional cancer centers and collaborating with other institutions will be necessary to enroll more patients and gather comprehensive data, Forsyth explains.

Forsyth emphasizes the potential for dendritic cells in the management of leptomeningeal disease, expressing optimism about the therapy’s effects. Although this study is an initial step, adding other therapeutic agents, such as antibody therapies, to the dendritic cells may enhance their efficacy, Forsyth says. This approach underscores a broader strategy to innovate and intensify treatments for leptomeningeal disease.

The first step towards curing this disease is a commitment to understanding and addressing it with serious, dedicated efforts, Forsyth argues. He stresses the importance of leveraging the field of immune-cellular therapies, noting that Moffitt Cancer Center’s substantial program in this area positions them well to tackle leptomeningeal disease with new vigor. The ability to apply this potent therapeutic approach specifically to leptomeningeal disease for the first time marks a hopeful new chapter in the fight against this challenging condition, he concludes.