Date: 2016-11-14
Type of information: Presentation of results at a congress
phase: 1-2
Announcement: presentation of results at the 2016 Annual Meeting of the Society for Immunotherapy of Cancer (SITC)
Company: Inovio Pharmaceuticals (USA - PA) University of Pennsylvania (USA - PA)
Product: INO-3112
Action
mechanism: immunotherapy product. INO-3112, an active immunotherapy targeting HPV 16/18 combined with a DNA plasmid for IL-12 as an immune activator, is designed to activate patients’ immune responses to specifically target and kill HPV associated tumors. In August 2015, Inovio licensed INO-3112 to Medimmune for an upfront payment of $27.5 million, $700 million in potential development and commercial milestone payments, and royalties on INO-3112 product sales.
Disease: head and neck squamous cell cancer
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: This Phase I/IIa, open-label study is evaluating the safety, tolerability, and immunogenicity of INO-3112 DNA vaccine delivered by electroporation to subjects with HPV associated head and neck squamous cell cancer. This open label study is intended to assess the safety, tolerability, and immunogenicity of INO-3112 in up to twenty five adults with HPV-positive head and neck squamous cell carcinoma. Additionally, the study is evaluating the anti-tumor response and progression free survival of patients. The first group enrolled six subjects who were treated with INO-3112 before and after resection of their tumor. One subject withdrew consent after surgery, leaving five evaluable subjects in this group. All of these subjects received one dose of INO-3112 (averaging 14 days and ranging 7 to 28 days) prior to definitive surgery plus three additional doses post-surgery. The second group enrolled sixteen subjects who received four doses of INO-3112 after at least two months following completion of definitive chemoradiation or surgery and adjuvant chemoradiation therapy. (NCT02163057)
Latest
news: * On November 14, 2016, Inovio Pharmaceuticals announced an interim data analysis showing that its INO-3112 cancer immunotherapy product generated antigen-specific CD8+ killer T-cell responses measured both in tumor tissue and in peripheral blood from subjects with head and neck cancer associated with human papillomavirus. The immunology results show that INO-3112 treatment generated robust HPV16/18 specific CD8+ T cell responses in peripheral blood in four of five subjects who also showed increased T-cell activation in resected tumor tissue samples. These four subjects remained disease free in continuing follow-up that ranged from nine to 24 months at the time of analysis. One subject with only minimal increases in T cell immune responses developed progressive disease at 11 months post start of the study. These results were presented November 12th at the 2016 Annual Meeting of the Society for Immunotherapy of Cancer (SITC) in National Harbor, Maryland. This poster presentation provided immune response and disease free survival data from the first treatment group. CD8+ and FoxP3 T cell expression were evaluated in tumor samples obtained before and after surgery. In addition, ELISpot analysis was performed to determine the number of T cells capable of secreting IFN-? in response to HPV antigen stimulation. Four of five subjects had robust T cell response as measured by blood ELISpot assay and the same four subjects also showed an average increase of 60% of CD8+ to FoxP3 ratio measured by immunohistochemistry post vaccination, demonstrating increased infiltration of CD8+ T cells as well as reduction of regulatory T cells measured by FoxP3 expression in tumor tissue. These four subjects remained disease free with follow-up ranging from nine to 24 months to date. One subject with only a marginal increase in ELISpot response magnitude to HPV and no increase in CD8+/FoxP3 ratio in tumor tissue post INO-3112 developed progressive disease at 11 months post-treatment. Overall the characteristics of these immune response data mirrored those previously observed in a phase IIb clinical study of VGX-3100 for HPV-associated cervical dysplasia. In that study, strong CD8+ T cell immune responses were positively correlated with achievement of primary and secondary efficacy endpoints. VGX-3100 is the first therapy to demonstrate that activated killer T cells induced in the body have the power to clear neoplastic lesions as well as the virus which caused the disease. Inovio is continuing subject monitoring and comprehensive immune analyses for both cohorts of this study and expects multiple reports of additional data throughout 2017.* On November 5, 2015, Inovio Pharmaceuticals announced an interim data analysis showing that its INO-3112 DNA-based immunotherapy generated specific T-cell responses and was well tolerated in all evaluable patients with head and neck cancer associated with human papillomavirus (HPV) types 16 and 18. The immunology results show that INO-3112 generated robust HPV16/18 specific CD8+ T cell responses and antibodies against HPV16/18 in all 10 tested patients who received all treatments. These results will be presented at the 30th Anniversary Annual Meeting of the Society for Immunotherapy of Cancer in National Harbor, MD and on Nov 20-22 at the European Society for Medical Oncology Symposium on Immuno-Oncology in Lausanne, Switzerland. In this phase I/IIa study, patients with HPV positive head and neck cancer received INO-3112 once every three weeks for a total of four injections. The characteristics of these immune response data mirror those previously observed in a phase II clinical study of VGX-3100 for HPV-associated cervical dysplasia. In that study, strong CD8+ T cell immune responses were positively correlated with achievement of primary and secondary efficacy endpoints. Data from that trial was recently published in The Lancet . This publication details that VGX-3100 is the first therapy to demonstrate that activated killer T cells induced in the body have the power to clear neoplastic lesions as well as the virus which caused the disease. The study currently continues patient enrollment at Abramson Cancer Center of University of Pennsylvania in Philadelphia.
