Key points are not available for this paper at this time.
Abstract BACKGROUND Leptomeningeal disease (LMD) is a devastating complication of BC has a dismal prognosis. The CSF of LMD pts have an innate (PMID:34035069), but not adaptive, immune response (bioRxiv 2023.03.17.533041; doi: https://doi.org/10.1101/2023.03.17.533041) that is insufficient to combat LMD. We used IT cDC1 to elicit an adaptive response in LMD and found they were safe, induced a Th1 response, cured most HER2+ LMD, and prevented LMD recurrence (PMCID: 9354231). Responses were CD4+ and B cell dependent. cDC1s induce Th1 responses in HER2/HER3 tumors (PMID: 35710296; PMID: 34785506). And there are trials of cDC1s in BC patients (e.g.NCT03384914, NCT03387553, etc.) We hypothesized that a RP2D would be found and the CSF would be remodeled to have a Th1 immunological profile. METHODS Phase I single-arm, dose escalation multicenter study to establish 1) safety of IT cDC1s, and 2) associations between clinical outcomes & translational CSF studies (e.g. scRNAseq, cytokine arrays). Eligibility includes TNBC or HER+ LMD pts, prior pCSpRT/WBRT, ECOG ≤2, normal organ function, life expectancy of ≥ 8 weeks, and an Ommaya. IT cDC1s were administered weekly x 12 wks at one of 4 dose levels (1 X 106 – 5 X 107 cDC1s) until PD, DLT or withdrawal. Primary Endpoints were 1) safety and DLTs, 2) association between clinical endpoints and immune profiles. We used the BOIN design for the MTD. Response was measured using RANO-LM (PMID: 30715514). DLTs were defined as ≥ gr. 3 not due to LMD, resistant to medical intervention/CSF removal. Final pre & post cDC1 treatment cyto/chemokine & scRNAseq will be determined. As of 04 01 2024, 4 pts were treated 3 pts cohort 1 @ 1 X 106 & 1 pt cohort 2 @ 2 X 106. NCT05809752. Sponsor: Department of Defense
Forsyth et al. (Thu,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: