Phase 2 study of sl-701, a novel immunotherapy, in adults with recurrent GBM: A high parameter flow cytometry analysis of cd8+ t cells and potential implications for patient enrichment strategies

Document Type

Conference Proceeding

Publication Date

11-12-2021

Publication Title

Neuro Oncol

Keywords

carboxymethylcellulose polycytidylic polyinosinic acid polylysine, endogenous compound, programmed death 1 receptor, transcriptome, adult, cancer recurrence, cancer staging, cancer survival, CD8+ T lymphocyte, cell membrane potential, clinical outcome, conference abstract, drug safety, female, flow cytometry, gene expression, genetic transcription, glioblastoma, high throughput sequencing, human, human cell, human tissue, immunocompetence, immunotherapy, major clinical study, male, multicenter study, overall survival, phase 2 clinical trial, preliminary data, protein expression, survivor

Abstract

Treatment of glioblastoma (GBM) remains a critical challenge and unmet medical need due to limited treatment options. SL-701 is a novel immunotherapy comprised of synthetic peptides designed to elicit a target-specific anti-tumor immune response against the GBM antigens IL-13Rα2, ephrinA2, and survivin. A multicenter, 2-stage, phase 2 clinical trial (NCT02078648) that evaluated the safety and efficacy of SL-701 in 74 adults with recurrent GBM was previously reported. This report describes preliminary data to suggest a correlation of immunocompetence to clinical outcome. In stage 2 (SL-701 + bevacizumab + poly-ICLC) the overall survival at 12 months was 50%. Two of 28 patients enrolled in stage 2 achieved CR (duration of response: 7.8 and 8.8 months) and 2 achieved PR (duration of response: 7.9 and 8.8 months). In a preliminary analysis to assess CD8+ T-cell responses, long-term survivors were comprised largely of subjects with an SL-701-induced target-specific CD8+ T-cell response, indicating a potential correlation of immunocompetence to clinical outcome. By week 24, SL-701-induced target-specific CD8+ T cells expressing IFNg were detected in 8 of 27 patients (30%) who had sufficient samples, with co-expression of PD-1, TIM3, and LAG3 detected in 4 patients. To further understand the T-cell response to SL-701, deep sequencing of target-specific CD8+ T cells using whole transcriptome-based molecular cytometry and high parameter (25+ color) flow cytometry is currently underway and updated data will be reported.

PubMed ID

Not assigned.

Volume

23

Issue

SUPPL 6

First Page

vi51

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