1063PASET STUDY: FINAL RESULTS OF PATIENTS WITH LOCALLY RECURRENT OR METASTATIC RENAL CELL CARCINOMA (RCC) TREATED WITH MGN1601

Abstract Aim: Allogeneic tumor cells gene-modified via MIDGE® vectors to express IL-7, GM-CSF, CD80, and CD154, immunomodulated with dSLIM® constitute the therapeutic cancer vaccine MGN1601, whose safety, immunological effects, and clinical efficacy were assessed in heavily pre-treated patients with RCC. Methods: The multicenter, single-arm phase 1/2 ASET study consisted of 8 vaccinations over 12 weeks during the treatment phase (TP). Following re-evaluation, patients with at least disease stabilization entered an extension phase (EP, 5 vaccinations until week 120). Overall, 19 patients were included and received at least one MGN1601 injection (ITT); 17 had ≥3 lines of previous therapy. Results: The TP was completed by 10 of 19 patients (53%) per-protocol (PP). Only 9.2% (10/109) of adverse events were drug-related and no drug-related serious adverse event was reported. Two patients achieved disease control after TP and continued in EP: One had PD after 48 weeks, the other remained in sustained partial response for over 120 weeks. Median OS was 24.8 weeks for ITT and 115.3 weeks for PP. Analysis of baseline characteristics revealed absolute lymphocyte counts, neutrophil to lymphocyte ratios, platelets, MSKCC score, and liver metastasis as putative predictive factors of longer overall survival. Immunological analyses revealed improved immune function during MGN1601 treatment: Patients' PBMC showed a significant increase in IL-2 secretion in 7 of 10 analyzed patients upon stimulation with recall antigens. Re-stimulation of patients' PBMC with MGN1601 cells or peptide mixes of tumor associated antigens resulted in >2-fold increase of IFN-gamma secreting cells in 4 of 9 patients. Four of 5 patients showed an increase of single activation marker and all 5 patients developed vaccine cell binding antibodies. Conclusions: Administration of MGN1601 was safe, improved patients' immune function and showed promising OS in a subgroup of heavily pretreated RCC patients who could receive therapy over 12 weeks (PP population). These results warrant further evaluation in a larger, controlled trial. Baseline biomarkers may allow identifying patients more likely to benefit from this vaccination. Disclosure: K. Kapp: is an employee of Mologen AG; M. Schroff: is CEO of Mologen AG; M. Schmidt: is an employee of Mologen AG; B. Wittig: has share ownership in Mologen AG and has received research funding from Mologen AG. All other authors have declared no conflicts of interest.