1078TiPPHASE II STUDY WITH IMMUNOTHERAPY WITH DENDRITIC CELLS (DC) COMBINED WITH INTRATUMORAL HILTONOL IN PATIENTS WITH ADVANCED CANCER

ABSTRACT Background: DC vaccines are active treatments for cancer and combination strategies are expected to increase anti-tumor activity. We explored the efficacy of intratumoral Hiltonol, a potent TLR3 agonist, combined with an autologous vaccine of DC loaded with self-tumor lysates that we developed in a previous study (Alfaro C, J Immunology 2011). Hiltonol is an stabilized form of polyI:C, a nucleic acid that mimics viral RNA. It induces local release of cytokines which promote inflammation, increase type I interferon secretion and stimulate leukocyte migration to infiltrate tissues. Preclinical data indicates that intratumoral Hiltonol activates pro-inflammatory changes that increase the efficacy of DC vaccination. Trial design: In this ongoing phase II study, 25 patients with advanced solid tumors non-amenable for conventional treatment are being treated with Hiltonol and DC vaccinations. Our vaccination protocol includes the following strategies: a) pretreatment with cyclophosphamide to decrease regulatory T cells; b) maturation and activation of DC with TNF-alpha, interferon-alpha and poly I:C, to induce type I interferon; c) use of autologous tumor as antigenic source to expose DC to antigens that are exclusive of tumor cells; and d) daily intradermal doses during four consecutive days in 2 cycles every 4 weeks. Two intratumoral ultrasound-guided injections of Hiltonol 0.25 mg are being administered on alternate days one week following each DC cycle. Sample size has been calculated using a two-stage Simons Minimax design, with alpha error a= 0.05 and beta-error = 0.10 for P0 = 0.05 and P1 = 0.25. The main objective is response rate. Secondary objectives include assessment of toxicity, overall survival and immunologic response (in vitro lymphocyte responses against tumor antigens; delayed hypersensitivity reactions; and assessment of DC maturation by expression of pro-inflammatory cytokines) (ClinicalTrials.gov Identifier: NCT01734564). This abstract was accepted and previously presented at the 2014 ASCO Annual Meeting Chicago, June 2014 (TPS3113). Disclosure: All authors have declared no conflicts of interest.