5380 - Results of Phase 2 Trial of SL-701, a novel immunotherapy targeting IL-13Ra2, EphA2, and survivin, in adults with second-line recurrent glioblastoma (GBM)

Background

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.

Methods

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.

Results

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.

Conclusions

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

NCT02078648.

Legal entity responsible for the study

Stemline Therapeutics.

Funding

Stemline Therapeutics.

Editorial Acknowledgement

Disclosure

R. Lindsay, J. Bullington, C. Brooks: Employment and stock ownership: Stemline Therapeutics. All other authors have declared no conflicts of interest.