OS2.7 An open-labelled, randomized phase II study in patients with recurrent Glioblastoma Multiforme comparing progression free survival of ALECSAT (Autologous lymphoid effector cells specific against tumour-cells) versus Bevacizumab/Irinotecan

Abstract

Background: The aim of this study was to investigate the efficacy of ALECSAT (Autologous lymphoid effector cells specific against tumour‐cells) in patients with recurrent glioblastoma multiforme (GBM). ALECSAT is a cell based medical product formulated as a patient specific suspension for injection. The activated immune cell suspension targets a group of cancer/ testis antigens and contains Natural Killer cells. More specifically, ALECSAT is composed of viable human cells of autologous origin, which undergo a manufacturing process, where lymphocytes with specificity for and killing ability towards tumour cells are isolated from a patient's blood sample. The cells derived from one single study patient can only be administered to the same. The derived cells are activated and expanded in numbers. The tumour specific lymphocytes are prepared in 20‐26 days. Methods: A prospective, open‐label, phase II study was designed to include 175 patients with recurrent GBM in three centres in Denmark. The patients were randomized 3:2 to ALECSAT (donation of blood product 3 weeks prior to each treatment at weeks 4, 9, 14, 26 and 46) compared to Bevacizumab (10mg/kg every 2 weeks) and Irinotecan (125mg/m2 every2 weeks). Treatment duration was planned for up to 62 weeks or progression for ALECSAT and progression for Bevacizumab/Irinotecan. In the ALECSAT arm crossover was permitted. The primary endpoint was progression free survival (PFS) evaluated by RANO criteria. Secondary endpoints were overall survival (OS), quality of life (evaluated by EORTC QLQ‐C30) and objective response rate. Statistical tests using a two‐sided t‐test at a 5% significance level Results: The study terminated early after a pre‐planned interim analysis and the results from 25 patients were analysed. Fifteen patients were treated in the ALECSAT arm and ten patients in the Bevacizumab/Irinotecan arm. Median PFS was 1.0 month in the ALESCAT group compared to 5.4 months in the Bevacizumab/Irinotecan group (HR: 0.16, CI: 0.05‐0.49, p < 0.001). Median OS was 5 months in the ALECSAT group and 6.8 months in the Bevacizumab/Irinotecan group (HR: 0.45, CI: 0.12‐1.54, p = 0.19). No patients in the ALESCAT group had objective response by RANO compared to six patients in the Bevacizumab/Irinotecan group. Quality of life was similar in the two groups. Both treatments were well tolerated. The main toxicity was grade 3 diarrhea in the Bevacizumab/Irinotecan group (8 patients compared to 1 patient in the ALECSAT group) Conclusion: ALECSAT treatment of patients with recurrent GBM provided no PFS or OS prolongation. Moreover, no objective responses were found. This may be due to the fact, that ALECSAT was administered 28 days later than the treatment in the control group was initiated. The ALECSAT treatment appeared well tolerated and no safety concerns were raised. In this study set up ALECSAT does not seem to have effect as an isolated component in recurrent GBM.