CTIM-06. A PHASE 2 STUDY OF A NOVEL IMMUNOTHERAPY SL-701 IN ADULTS WITH RECURRENT GLIOBLASTOMA: EXPLORING THE PROGNOSTIC VALUE OF TREATMENT-INDUCED CD8+CD57+ T-CELLS AS A MARKER FOR SURVIVAL

Abstract

Abstract Recurrent glioblastoma (GBM) remains a challenging disease with limited therapeutic options and poor prognosis. SL-701 is a novel immunotherapy composed of synthetic peptides designed to elicit an anti-tumor immune response against the overexpressed GBM antigens IL-13Rα2, ephrinA2, and survivin. In this study, we present updated findings from a phase 2 clinical trial (NCT02078648) evaluating SL-701+poly-ICLC+bevacizumab, where the 12-month overall survival (OS) was 50%. Using high-parameter flow cytometry, we compared the quality of the treatment induced T-cell response in patients with an OS < 12m (n = 15) versus OS >12m (n = 12). Among the patients assessed, 89% exhibited heterogeneous T-cell responses against SL-701, with no discernible correlation between the response to a specific peptide and survival. Consequently, we focused on identifying other characteristics of the pan-SL701-specific T-cell response with an association to survival. Assessing all time points collected, patients with an OS >12m generated a significantly higher frequency of SL-701-specific CD8 T-cells (79% increase, P < 0.005) and a lower frequency of CD4+ T-cells (36% decrease, P < 0.05) compared to patients with a lower OS. Moreover, the ratio of CD8:CD4 T-cells was 2-fold higher in patients with an OS >12m indicating a CD8-enriched response, whereas patients with an OS < 12m had a lower ratio of CD8:CD4 associated with CD4 enriched responses. Notably, patients with an OS >12m, expressed CD57 (identifying highly cytotoxic, differentiated memory T-cells) on 40% of their T-cells compared to 18% in patients with an OS < 12m (P < 0.05). Furthermore, the ratio of SL-701 specific CD57:CD107A expressing cells trended 20% lower in patients with an OS >12m, indicative of a replicating, cytotoxic T-cell response that is not terminally differentiated. These qualitative differences in the immune response, detectable as early as week 8 post treatment, may serve as biomarkers for monitoring and predicting survival. Deep sequencing of SL-701-specific T-cells is planned.