Work

Bsld-02 a First in Human Phase I Trial of Intrathecal Dendritic Cells Primed Against Her2/her3 in Patients With Leptomeningeal Disease From Triple-negative or Her2+ Breast Cancer Show Development of Adaptive Immune Responses

Year: 2025

Type: article

Abstract: BACKGROUND The CSF of patients with LMD have an innate, but not adaptive, immune cellular profile. Murine LMD models showed IT cDC1s were safe, induced a Th1 response (CD4+ > CD8+ T cell and B cell dependent), cured most HER2+ LMD, and prevented LMD recurrence. We conducted a Phase I study of IT DCs and hypothesized the CSF would be remodeled to have a Th1 adaptive immunological profile. METHODS This is a Phase I single-arm, dose escalation study to establish 1) the safety and 2) associations between clinical outcomes & translational CSF studies. Eligibility includes TNBC or HER+ LMD pts, prior pCSpRT/WBRT, ECOG PS ≤2, and Ommaya reservoir. IT cDC1 IT were administered weekly x 12 at one of 4 dose levels (1 x 106 – 5 x 107) until PD/DLT. Endpoints were 1) safety, MTD RP2D, 2) association between clinical and immune profiles in the CSF. DLTs were defined as ≥ gr. 3 not due to LMD & didn’t respond to intervention. RESULTS As of 03/15/25, the first 6 patients received 1 x 106 – 2 x 107 DCs with no DLTs. Headaches were common and grade 3 in two (33%) patients. Two (33%) had PD of LMD within 13 weeks. One patient died from leukoencephalopathy. The median OS was 48.0 weeks and five (83%) are alive. CSF cytokines Th1 cytokines included IFN-g, IL-6, IL-12, TNF-a; Th2-related IL-4 was not elevated. Transcriptomics showed a marked increase in CD4+ T, CD8+ T and B cells with a reduction of tumor cells. Antibodies to HER2 or HER3 developed in four of five (80%) patients. CONCLUSION Our results suggest this approach activates CD4+ Th1 adaptive immune responses that drives adaptive antitumor activity which is otherwise lacking in LMD (NCT05809752).

Source: Neuro-Oncology Advances

DOI: 10.1093/noajnl/vdaf123.014