1078TiP - Phase II study with immunotherapy with dendritic cells (DC) combined with intratumoral hiltonol in patients with advanced cancer

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Immunotherapy
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter ALFONSO Gurpide
Citation Annals of Oncology (2014) 25 (suppl_4): iv361-iv372. 10.1093/annonc/mdu342
Authors A. Gurpide1, J.M. Lopez-Picazo2, C. Alfaro3, M.E. RodrÍguez-Ruiz2, J.L. Perez Gracia4, M. Fernandez de Sanmamed2, A. Benito5, D. Cano6, A. Gonzalez7, I. Rodriguez Lopez8, J.P. Fusco2, J. Rodriguez2, S. Martin Algarra2, R. Martínez-Monge2, I. Melero9
  • 1Oncology, Clinica Universidad de Navarra, 31008 - Pamplona/ES
  • 2Oncology Department, Clinica Universidad de Navarra, 31008 - Pamplona/ES
  • 3Immunotherapy, Centro de Investigacion Medica Aplicada, pamplona/ES
  • 4Clinical Oncology, Clinica Universitaria de Navarra, 31008 - Pamplona/ES
  • 5Radiology, clinica universidad de navarra, Pamplona/ES
  • 6Radiology, clinica universidad de navarra, pamplona/ES
  • 7Bioquimica, clinica universidad de navarra, pamplona/ES
  • 8Immunotherapy Group, centro de investigacion medica aplicada, pamplona/ES
  • 9Immunotherapy, clinica universidad de navarra, pamplona/ES



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 Simońs Minimax design, with alpha error α= 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).


All authors have declared no conflicts of interest.