Phase 2 trial of SL-701, a novel immunotherapy comprised of synthetic short peptides against GBM targets IL-13ra2, EPHA2, and survivin, in adults with second-line recurrent GBM
Reardon D, Nabors B, Kumthekar P, Badruddoja M, Fink K, Lieberman F, Hu J, Dunbar E, Walbert T, Schiff D, Sherman J, Tran D, Ashby LS, Butowski N, Iwamoto F, Moertel C, Schulder M, Chen J, Bullington J, Shemesh S, Brooks C, Goswami T, and Peereboom DM. Phase 2 trial of SL-701, a novel immunotherapy comprised of synthetic short peptides against GBM targets IL-13ra2, EPHA2, and survivin, in adults with second-line recurrent GBM. Neuro-Oncology 2017; 19(suppl 6):vi28.
BACKGROUND: SL-701, a novel immunotherapy comprised of synthetic peptides elicits immune responses against overexpressed GBM targets: interleukin-13 receptor alpha-2 (IL-13Rα2), EphrinA2 (EphA2), and Survivin. Updated data reported from a multicenter, 2-stage Phase 2 clinical trial of SL-701 in HLA-A2+ adults with relapsed GBM. METHODS: Patients enrolled had KPS > 60 and failure of standard RT/TMZ. Stage 1: SL-701 was administered with adjuvants GM-CSF and imiquimod biweekly for 6 months, then q28 days. Stage 2: SL-701 and adjuvant poly-ICLC were administered biweekly with bevacizumab (10 mg/kg). Primary objectives include: safety and tolerability, investigator assessed objective response rate (ORR) using RANO criteria and 12 month-survival rate. RESULTS: As of 16May2017, 74 patients (46 in Stage 1 and 28 in Stage 2) received SL-701. Accrual for Stage 1 and 2 is complete. Patients were 100% bevacizumab naïve, 65% male with a median age of 56 years (range: 24-79). Patients received a median of 8.5 doses. The most frequent grade 3-4 treatmentrelated adverse event was fatigue (n = 2; 2.7%). Among 46 evaluable Stage 1 patients, 1 partial response (PR; duration: 78 weeks) and 15 stable disease (SD; median duration: 16 weeks; range: 1.3 - 99 weeks) were observed. Of 28 evaluable Stage 2 patients, 21% ORR consisting of 2 complete response (CR; duration: 30 and 46 weeks, respectively) and 4 PR (median duration: 31 weeks; range: 12 - 47 weeks) was observed with 19 SD (median duration: 14 weeks; range: 0.1 - 41 weeks) achieved. Median overall survival (mOS) of 11.2 and 11.7 months was observed for Stage 1 and 2 patients, respectively with a 25% survival probability at 14 weeks. SL-701 plus adjuvants with or without bevacizumab have a manageable safety profile with anti-tumor activity, several CRs, and a preliminarily promising survival curve, warranting further study. Updated study data will be presented.