
==== Front
Neurooncol Adv
Neurooncol Adv
noa
Neuro-Oncology Advances
2632-2498
Oxford University Press US

10.1093/noajnl/vdae090.018
vdae090.018
Final Category: Basic Science Leptomeningeal Disease
AcademicSubjects/MED00300
AcademicSubjects/MED00310
BSLM-07 A FIRST IN HUMAN PHASE 1 TRIAL OF DOSE ESCALATING INTRATHECAL (IT) DENDRITIC CELLS (CDC1S) PRIMED AGAINST HER2/HER3 IN PATIENTS (PTS) WITH LEPTOMENINGEAL DISEASE (LMD) FROM TRIPLE NEGATIVE (TNBC) OR HER2+ BREAST CANCER (BC)
Forsyth Peter Moffitt Cancer Center, Tampa/FL, USA

Gandhi Shipra Roswell Park Comprehensive Cancer Center, Buffalo/NY, USA

Wilcox Jessica Memorial Sloan Kettering Cancer Center, New York/NY, USA

Law Vincent Moffitt Cancer Center, Tampa/FL, USA

Mo Qianxing Moffitt Cancer Center, Tampa/FL, USA

Chen Zhihua Moffitt Cancer Center, Tampa/FL, USA

Ahmed Kamran Moffitt Cancer Center, Tampa/FL, USA

Piteo Cecily Moffitt Cancer Center, Tampa/FL, USA

Evernden Brittany Moffitt Cancer Center, Tampa/FL, USA

Pina Yolanda Moffitt Cancer Center, Tampa/FL, USA

Boire Adrienne Memorial Sloan Kettering Cancer Center, New York/NY, USA

Kalinski Pawel Roswell Park Comprehensive Cancer Center, Buffalo/NY, USA

Czerniecki Brian Moffitt Cancer Center, Tampa/FL, USA

8 2024
02 8 2024
02 8 2024
6 Suppl 1 2024 SNO/ASCO CNS Metastases Conference i6i6
© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

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
==== Body
pmc
