Ctim-11. 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
Year: 2021
Type: conference-abstract
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.
Source: Neuro-Oncology
Authors: David Peereboom, Ross Lindsay, Michael Badruddoja, L Burt Nabors, Priya Kumthekar, Frank Lieberman, David Tran, Surasak Phuphanich, David Schiff, Jonathan Sherman, Nicholas Butowski, Erin Dunbar, Karen Fink, Fabio Iwamoto, Christopher Moertel, Michael Schulder, Tobias Walbert, Nassir Habboubi, Krzysztof Grzegorzewski, Christopher Brooks, David Reardon
Institutions: Cleveland Clinic, Stemline Therapeutics (United States), Center for Neurosciences, University of Alabama at Birmingham, Northwestern Medicine, UPMC Hillman Cancer Center, University of Florida, University of California, San Francisco, Piedmont Cancer Institute, Baylor Scott & White Health, Columbia University, University of Minnesota, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, Henry Ford Health, Dana-Farber Cancer Institute
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W3217040851