SL-701 is a novel immunotherapy comprised of synthetic peptides designed to elicit an anti-tumor immune response against targets overexpressed in glioblastoma (GBM): interleukin-13 receptor alpha-2, ephrinA2 and survivin. Updated phase 2 data are reported.
Patients enrolled had recurrent GBM, were HLA-A2+ and bevacizumab (bev)-naïve, and had KPS>60. In Stage 1, SL-701 was administered with adjuvants GM-CSF and imiquimod biweekly for 6 months, then q28 days. In Stage 2, SL-701 and adjuvant poly-ICLC were administered biweekly with bev (10 mg/kg) for 6 months, then q28 days. Primary objectives included safety, tolerability, investigator-assessed objective response rate (ORR) using RANO criteria, and 12-month overall survival rate (OS-12). SL-701-specific CD8+ T cells in PBMCs isolated from patients were assessed by flow cytometry using antibodies to CD3, CD4, CD8, IFNg, TNFa, IL-2, and PD-1.
Accrual for Stages 1 and 2 is complete. 74 patients [46 in Stage 1 and 28 in Stage 2; 65% male, median age of 57 years [(range: 24-79)] received SL-701. Five patients received SL-701 on compassionate use basis. The most frequent treatment-related adverse events (TRAEs) were fatigue (22%) and injection site reaction (18%). The most frequent grade 3-4 treatment-related adverse event was fatigue (n = 2; 2.7%). In Stage 1, a 22% disease control rate (DCR; CR+PR+SD for > =8 weeks) was observed, comprised of 1 PR (duration: 78 weeks) and 9 SD [median duration: 25 weeks (range: 3.7–120.9)] were observed. In Stage 2, a 54% DCR was observed consisting of 2 CRs (duration: 22 and 46 weeks), 2 PRs (duration: 38 and 54 weeks), and 11 SDs [median duration: 13.6 weeks (range: 1.6 – 35.1)] were observed. OS-12 was 44% in Stage 1 [95% CI 28.9, 58.9] and 50% [95% CI 30.6, 69.4] in Stage 2, and median OS was 11 months in Stage 1 and 11.7 months in Stage 2. Flow cytometry analysis of Stage 2 patients demonstrated CD8+ T cell responses to the SL-701 peptides.
SL-701 plus adjuvants with or without bevacizumab was well-tolerated and demonstrated anti-tumor activity, including multiple major responses and a preliminarily promising survival curve, warranting further study. Updated study data will be presented.
Clinical trial identification
Legal entity responsible for the study
R. Lindsay, J. Bullington, C. Brooks: Employment and stock ownership: Stemline Therapeutics. All other authors have declared no conflicts of interest.