Dr Forsyth on a Phase 1 Study Evaluating Intrathecal cDC1s in Leptomeningeal Disease

"We are lucky that we have seen people quickly and early, so they're still in pretty good shape. Sometimes when people have this disease, it's too advanced by the time you see them or by the time they get the appropriate care, because it's hard to recognize this disease. It's a huge challenge."

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

This ongoing trial employs a standard 3 + 3 dose-escalation design, with an initial safety cohort at a low dose and escalates to 4 dose levels, Forsyth begins. Patients will receive intrathecal dendritic cells weekly for 12 weeks, with doses ranging from 1 x 10⁶ to 5 x 10⁷ cells. To enroll onto the study, patients must be 18 years of age or older and have leptomeningeal disease from TNBC or HER2-positive breast cancer, an ECOG performance status of 3 or lower, and a life expectancy of at least 8 weeks, he says.

Safety and dose-limiting toxicities are the primary end points, Forsyth continues. Secondary end points include survival beyond 15 weeks, response rates, immune response markers such as IFNγ, and the presence and activation status of immunocytes and tumor cells in cerebrospinal fluid, he details. Early data from the study were presented at the 2024 ASCO Annual Meeting.

The trial benefits from early patient recruitment, enabling treatment at a less advanced disease stage, Forsyth notes, adding that this is critical given the challenges of recognizing and managing leptomeningeal disease promptly.

Overall, this marks the first study exploring intrathecal immune cellular therapy specifically for leptomeningeal disease, a rare and challenging condition caused by cancer spreading to the membranes surrounding the brain and spinal cord. Continued data read out from this trial could provide valuable insights into the safety and efficacy of immune cellular therapy in this high-need population.