Abstract LB-233: Immune-related efficacy data of the phase 1-2 study of an with fourfold gene-modified allogeneic tumor cell based vaccine in patients with advanced renal cell carcinoma
Authors: Weith Ekaterina , Tschaika Marina , Weikert Steffen , Gruenwald Viktor , Schmidt-Wolf Ingo GH , Hauser Stefan , Schroff Matthias , Kapp Kerstin , Schmidt Manuel , Wittig Burghardt 
Published: August 2012

Abstract
Background. The first-in-man phase 1-2 clinical study (ASET study) of the cell-based therapeutic cancer vaccine MGN1601 included patients with advanced renal cell carcinoma (RCC) who failed previous therapies and had no further standard therapy available. MGN1601 consists of two active pharmaceutical ingredients in fixed combination: fourfold gene-modified allogeneic tumor cells expressing IL-7, GM-CSF, CD80 and CD154 through MIDGE® vectors and a TLR-9 agonist, the DNA-based immunomodulator dSLIM®. Methods. The ASET study is conducted as a multicentric, open, single-arm Phase 1-2 clinical trial. Clinical response (PD, SD, PR, CR) was evaluated using CT scans according to RECIST 1.1 criteria and immune related Response Criteria (irRC). The efficacy data were evaluated in terms of progression-free survival (PFS) and overall survival (OS) for the intended to treat (ITT) and the treated per protocol (TPP) populations of patients.Immune response was determined by the following parameters: ELISA of serum cytokines and chemokines, DTH to MGN1601, LTT assay to standard antigens, frequency and activation of plasmacytoid dendritic cells (pDC), myeloid dendritic cells (mDC), monocytes, natural killer cells (NK), NKT-, B-, and T cells. Blood mRNA and frequency of cytotoxic T cells by ELISPOT as well as tumor tissue were analyzed in a patient subgroup. Results. Nineteen patients, who had advanced stage RCC and failed up to 7 previous therapy lines (median 3 lines), were included. Nine of these patients completed the treatment phase per protocol (TPP), the others discontinued the study earlier due to PD. Currently, one patient is still in treatment phase. Median PFS in the TPP group was 12 weeks (3 months) and OS (not reached yet) 45 weeks (11 months). Three patients achieved disease control (one PR and two SD) after 12 weeks according to RECIST 1.1 criteria. Two patients are continuing treatment in the extension phase and are progression free since 37 and 46 weeks, respectively. Re-evaluation of tumor response data using irRC revealed one additional patient, who had a delayed tumor response 4 weeks after stop of treatment. Herewith, 4 out of 9 TPP patients (45%) achieved disease control. Of six patients receiving a targeted therapy following progress, four had substantial objective responses, suggesting that the study drug rendered their tumors more vulnerable to subsequent therapies. Immune analysis of the cell populations after 12 weeks showed trends towards increases of T cell, NKT-cell and pDC frequencies in those patients with clinical responses to the therapy, indicating anti-tumor immunity due to the study treatment. Conclusions. The therapeutic cancer vaccine MGN1601 shows promising efficacy in late stage mRCC patients. Results warrant further clinical studies with MGN1601.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-233. doi:1538-7445.AM2012-LB-233