OA13.06 Autologous Dendritic Cells Loaded with Allogeneic Tumor Cell Lysate (Pheralys®) in Patients with Mesothelioma: Final Results of a Phase I Study

Abstract

Mesothelioma is an aggressive malignancy without curative treatment options. We have previously shown promising activity of dendritic cell (DC) immunotherapy loaded with autologous tumor cell lysate (Hegmans 2013, Cornelissen 2016). Because of quality and quantity issues (availability, standardization etc) with the autologous lysate, we have developed an off-the-shelf allogenic tumor cell lysate from human mesothelioma cell lines (Pheralys®). Patients (pts) with advanced mesothelioma, either treatment naive, or non-progressing after chemotherapy, were included. Leucapheresis was performed to obtain an enriched monocyte fraction from which immature DC were generated which were loaded with the allogenic lysate. The DC were matured, frozen and stored. In subsequent cohorts of 3 pts 10, 25, or 50 × 106 DC were administered IV and intradermally, 3 times at a bi-weekly interval and after 3 and 6 months. Primary endpoint was toxicity occurring within 8 weeks after the first vaccination. Secondary endpoints were response rate (RR), progression free survival (PFS) and overall survival (OS). PFS and OS were determined from time of registration in the trial. Immunological read-outs were performed (DTH skin testing, peripheral blood testing). Nine pts (median age 69yrs, 8 male, 1 female) were included. All patients developed transient grade 1-fever and a grade 1-2 injection site reaction. No dose limiting toxicities or autoimmunity signs were observed. In 2 pts (22%), both treated with 25 ×106 cells, a partial response (PR) was observed, the other 7 pts had stable disease as best overall response. All patients are alive with a median follow up of 11.9 months after trial inclusion(range 7.6-16.5 months). Median PFS was 8.3 months (95% confidence interval (CI) 3.7-not yet reached), PFS at 12 months was 33% (95% CI 8%-62%). Data on immunological read outs are pending. DC immunotherapy with allogenic tumor cell lysate is safe and clinically active. Data on PFS and OS are promising and still maturing. The recommended dose for future studies will be 25 * 106 cells based on the responses and logistic reasons (the number of monocytes obtained during leucapheresis to generate 5 vaccinations). A randomized trial comparing DC therapy with Pheralys versus best supportive care as maintenance treatment after chemotherapy is planned to start in Q1 2017.