- Email: [email protected]
Phase Ii Study with Immunotherapy with Dendritic Cells (Dc) Combined with Intratumoral Hiltonol in Patients with Advanced Cancer
Annals of Oncology 25 (Supplement 4): iv361–iv372, 2014 doi:10.1093/annonc/mdu342.31
immunotherapy of cancer PHASE II STUDY WITH IMMUNOTHERAPY WITH DENDRITIC CELLS (DC) COMBINED WITH INTRATUMORAL HILTONOL IN PATIENTS WITH ADVANCED CANCER
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 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). Disclosure: All authors have declared no conflicts of interest.
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv371/2241788 by guest on 26 October 2019
A. Gurpide1, J.M. Lopez-Picazo2, C. Alfaro3, M.E. RodrÍguez-Ruiz2, J.L. Perez Gracia4, M. Fernandez de Sanmamed2, A. Benito5, D. Cano5, A. Gonzalez6, I. Rodriguez Lopez7, J.P. Fusco2, J. Rodriguez2, S. Martin Algarra2, R. Martínez-Monge2, I. Melero8 1 Oncology, Clinica Universidad de Navarra, Pamplona, SPAIN 2 Oncology Department, Clinica Universidad de Navarra, Pamplona, SPAIN 3 Immunotherapy, Centro de Investigacion Medica Aplicada, Pamplona, SPAIN 4 Clinical Oncology, Clinica Universitaria de Navarra, Pamplona, SPAIN 5 Radiology, Clinica Universidad de Navarra, Pamplona, SPAIN 6 Bioquimica, Clinica Universidad de Navarra, Pamplona, SPAIN 7 Immunotherapy Group, Centro de Investigacion Medica Aplicada, Pamplona 8 Immunotherapy, Clinica Universidad de Navarra, Pamplona, SPAIN
abstracts
1078TiP
immunotherapy of cancer PHASE II STUDY WITH IMMUNOTHERAPY WITH DENDRITIC CELLS (DC) COMBINED WITH INTRATUMORAL HILTONOL IN PATIENTS WITH ADVANCED CANCER
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 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). Disclosure: All authors have declared no conflicts of interest.
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv371/2241788 by guest on 26 October 2019
A. Gurpide1, J.M. Lopez-Picazo2, C. Alfaro3, M.E. RodrÍguez-Ruiz2, J.L. Perez Gracia4, M. Fernandez de Sanmamed2, A. Benito5, D. Cano5, A. Gonzalez6, I. Rodriguez Lopez7, J.P. Fusco2, J. Rodriguez2, S. Martin Algarra2, R. Martínez-Monge2, I. Melero8 1 Oncology, Clinica Universidad de Navarra, Pamplona, SPAIN 2 Oncology Department, Clinica Universidad de Navarra, Pamplona, SPAIN 3 Immunotherapy, Centro de Investigacion Medica Aplicada, Pamplona, SPAIN 4 Clinical Oncology, Clinica Universitaria de Navarra, Pamplona, SPAIN 5 Radiology, Clinica Universidad de Navarra, Pamplona, SPAIN 6 Bioquimica, Clinica Universidad de Navarra, Pamplona, SPAIN 7 Immunotherapy Group, Centro de Investigacion Medica Aplicada, Pamplona 8 Immunotherapy, Clinica Universidad de Navarra, Pamplona, SPAIN
abstracts
1078TiP