ATIM-06. PHASE 2 TRIAL OF SL-701 + BEVACIZUMAB IN PATIENTS WITH PREVIOUSLY TREATED GLIOBLASTOMA (GBM) MEETS PRIMARY ENDPOINT OF OS-12, WITH PRELIMINARY CORRELATION BETWEEN LONG-TERM SURVIVAL AND TARGET-SPECIFIC CD8+ T CELL IMMUNE RESPONSE

Abstract SL-701 is a novel immunotherapy comprised of synthetic peptides designed to elicit an anti-tumor immune response against GBM targets: interleukin-13 receptor alpha-2, EphrinA2 and Survivin. Updated Phase 2 data are reported. Patients with previously treated GBM, bevacizumab (bev)-naive, HLA-A2+, and KPS>60, were enrolled. SL-701 with adjuvant poly-ICLC was dosed biweekly with bev (10 mg/kg) for 6 months, then q28 days. Primary endpoint was OS-12, with statistical significance determined if lower bound of 2-sided 95% Clopper Exact confidence interval (CI) is >20%. Target-specific CD8+ T-cell frequency was assessed by flow cytometry. 28 patients received median of 13 SL-701 doses with bev. Most frequent treatment-related adverse events (TRAEs) were fatigue (39%) and injection site reaction (25%). Grade 3 TRAE was fatigue (3.6%); there were no other grade 3 TRAEs. Disease control rate (complete response [CR], partial response [PR], stable disease) was 54% (n=15), with 2 CRs and 2 PRs. Median duration of disease control was 8.8 months (95% CI 3.7, NE). Median OS was 11.7 months (95% CI: 7.1, NE). The primary endpoint was met with a 50% OS-12 (95% CI: 30.6, 69.4). Target-specific CD8+ T cell activity was detected at 8–24 wks, the majority occurring by wk 16. Long-term survivors were largely comprised of patients with target-specific CD8+ T-cell responses; median OS of these immune responders was not reached. The Phase 2 trial of SL-701 + bev in previously treated GBM met its primary endpoint with a 50% OS-12. The regimen was well-tolerated and demonstrated objective responses, including CRs. There was an even more pronounced survival signal, as well as an encouraging survival tail comprised largely of target-specific CD8+ T cell responders, and the median OS of these immune responders was not reached. Updates around next steps, including leveraging potential immune-related biomarkers in a registration-directed trial design, will be provided.