CTIM-29. PHASE 2 STUDY OF A NOVEL IMMUNOTHERAPY SL-701 IN ADULTS WITH RECURRENT GBM: IDENTIFICATION OF TREATMENT-INDUCED CD8+CD107A+ CD57+ PD-1- MEMORY T-CELLS THAT ARE ASSOCIATED WITH INCREASED SURVIVAL

Abstract

Recurrent glioblastoma (GBM) is an aggressive disease with poor survival and limited treatment options. SL-701 is a novel immunotherapy comprised of synthetic peptides designed to elicit an anti-tumor immune response against GBM antigens IL-13Rα2, ephrinA2, and survivin. Here we describe an 18-color flow cytometry analysis from stage 2 of a Ph2 clinical trial of SL-701+poly-ICLC+bevacizumab (NCT02078648), in which 12-month overall survival (OS) was 50%. Of the 27 patients in stage 2, 24 (89%) developed heterogeneous T-cell responses against 1, 2, or 3 of the SL-701 CD8 peptides. Magnitude and kinetics of peptide responses were variable among these patients with no clear relationship to OS. Therefore, a phenotypic analysis of the T-cell response in all 27 patients was conducted using terraFlow, a unique data analysis approach utilizing machine learning to identify T-cell phenotypes associated with clinical response from all possible combinations of markers. In total, 10,184 unique SL-701 induced phenotypes were measured, including 223 phenotypes (P < 0.05) and 16 core phenotypes that uniquely represent differences between patients with OS above or below 12 months (P < 0.05). 50% of the core phenotypes were CD8+ CD57+ CD107a+ PD-1- SL-701-specific T-cells, which are highly-differentiated memory T-cells primed for cytotoxicity. The frequency of the CD57+ core phenotypes (8%-18%) was enhanced 1.6- to 2.3-fold in patients with an OS > 12 months (P < 0.05). Similarly, 2 core phenotypes identified cytotoxic CD4+ and CD8+ T cells, which were enhanced 1.9- and 2.5-fold in patients with an OS >12 months. The final 6 core phenotypes identified activated CD4+ CD154+ SL-701-specific T-cells (5%-19%) that were enhanced 0.3- to 0.5-fold in patients with an OS < 12 months (P < 0.05), suggesting helper T-cell responses in the absence of cytotoxic T-cell responses are associated with an OS < 12 months. Deep sequencing of SL-701-specific T-cells using whole transcriptome-based molecular cytometry is planned.