Work

Syst-03 Phase 1b Study of Avelumab and Whole Brain Radiotherapy (wbrt) in Patients With Leptomeningeal Disease (lmd) From Epithelial Carcinomas: Final Results and Molecular Analyses With Single Cell Rna Sequencing

Year: 2023

Type: conference-abstract

Abstract: BACKGROUND LMD has a dismal prognosis with median overall survival (mOS) of 3-4 months (mo). Preclinical studies showed PD-1 axis blocking therapy promotes antigen presentation within the CSF compartment, and increases BBB permeability and ingress of activated T cells into the meninges/CSF space. In an open-label phase IB trial, we tested the safety and efficacy of Avelumab with WBRT in LMD (NCT0371768). METHODS Patients received Avelumab 800mg IV q2 weeks, up to 5 cycles (until PD or unacceptable toxicity) with WBRT 3000 cGy, 10 daily fractions. Primary endpoints were safety/DLTs and 3-mo OS. Secondary endpoints i.e., CSF T-cell transcriptome trajectory i.e., single cell RNA sequencing (scRNAseq). Patients with prior PD-1/PD-L1/CTLA-4/CD137 targeting therapy within 6mo were excluded. RESULTS 15 patients were enrolled i.e., breast (8), lung (4), nasopharyngeal (1), ovary (1), and pancreas (1). 87% female, median age 59 range 32-82. 1 patient did not complete WBRT. 2 out of 15 patients had gr. 3/4 immune-related AEs (i.e., hypoadrenalism, hypothyroidism, lymphopenia); 5 patients had treatment-related CONCLUSIONS Combination of Avelumab and WBRT is safe, well tolerated, and shows encouraging activity in LMD with an OS longer than other published series. Multiple platform interrogation of CSF will be used to explore mechanisms of LMD response and resistance. Functional studies of scRNAseq and short vs. long term survivors should be further explored.

Source: Neuro-Oncology Advances

DOI: 10.1093/noajnl/vdad070.111