Date: 2016-03-29
Type of information: update on patient enrollment
phase: 2
Announcement: update
Company: Inovio Pharmaceuticals (USA - PA) European Organization for Research and Treatment of Cancer (EORTC)
Product: INO-3112
Action
mechanism: immunotherapy product. INO-3112 consists of Inovio's HPV 16 and 18 immunotherapy (VGX-3100) and its IL-12-based immune activator (INO-9012). In this prospective, randomized, three arm phase II study, INO-3112 will be administered during standard chemo-radiotherapy (CRT) or during and after standard CRT as an adjuvant in patients with locally advanced cervical cancer.
Disease: locally advanced stage cervical cancer
Therapeutic area: Cancer - Oncology
Country:
Trial
details: The aim of this study is to assess the potential benefit of the addition of immunotherapy with VGX-3100 and INO-9012 (i.e. INO-3112) to concomitant CRT or, to concomitant CRT and continued as adjuvant in patients with locally advanced cervical cancer. Safety run-in: To test the safety of CRT combined with immunotherapy with INO-3112. This safety run-in phase will include the first 3 patients treated in each of the two INO-3112 combination arms who are exposed to at least two immunotherapy doses and evaluate whether the combination does not pose undue immediate risks to the patients further enrolled in the trial. Phase II:To demonstrate sufficient activity in the experimental combination arms to warrant a further phase III conclusive trial based on progression free survival (PFS) at 18 months assessed by RECIST by the local investigator. The efficacy will be assessed within each experimental arm while the standard arm will serve as a reference arm to check the reliability of the results. (NCT02501278)
Latest
news: * On March 29, 2016, Inovio Pharmaceuticals announced a clinical strategy update to take its INO-3112 HPV immunotherapy into human studies in combination with selected immunotherapy molecules from MedImmune, which is part of an existing partnership between the two companies. The companies intend to advance combination immunotherapies in populations with continued unmet need, the potential for a registrable endpoint, and an expedient clinical path. With these goals in mind, planned enrollment of a European Organization for Research and Treatment of Cancer (EORTC) trial to study cervical cancer patients with INO-3112 before and after chemoradiation in an adjuvant setting will not go forward. The EORTC collaboration was announced by Inovio prior to partnering with MedImmune in August 2015. * On July 23, 2015, Inovio Pharmaceuticals announced that it is collaborating with the European Organization for Research and Treatment of Cancer (EORTC) to evaluate Inovio's immunotherapy, INO-3112, in combination with traditional chemo-radiotherapy for the treatment of patients with locally advanced stage cervical cancer. The trial, primarily funded by the EORTC, is expected to begin by the end of the year. Partnership with the EORTC will offer Inovio clinical trial efficiency and speed in recruiting patients in Europe and in obtaining and analyzing results. The EORTC encompasses all aspects of cancer research, from translational research and new drug development to large phase III clinical trials and meta-analyses. EORTC is the only organization which carries out clinical studies throughout Europe for all types of cancer. Collaboration with the EORTC also leverages their connections to a network of more than 2,500 pre-clinical scientists and oncologists in more than 300 hospitals in over 30 countries. In this prospective, randomized, three arm phase II study, INO-3112 will be administered during standard chemo-radiotherapy (CRT) or during and after standard CRT as an adjuvant in patients with locally advanced cervical cancer. The primary endpoint is to demonstrate sufficient activity in the experimental combination arms to warrant a further pivotal phase III trial based on progression free survival (PFS) at 18 months. Efficacy will be assessed within each experimental arm while the standard arm will serve as a reference arm to check the reliability of the results. PFS at 18 months will be determined via RECIST criteria as assessed by the local investigator. The co-primary investigators are Georges Coukos, M.D. and Fernanda G. Herrera, M.D., both of whom are with the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland. Secondary endpoints include overall survival, clinical response, immunogenicity, tolerability and safety. This international study will enroll patients in several European countries and will complement and build on an Inovio-sponsored study already underway at several centers in the United States (Phase I/IIA, Open-Label, Safety, Tolerability, and Immunogenicity Study of INO-3112 Delivered by Electroporation in Women with Cervical Cancer after Chemoradiation for Newly Diagnosed Disease or Therapy for Recurrent and/or Persistent Disease). The efficacy and immunogenicity of VGX-3100, the basis of INO-3112, in patients with the precursor to cervical cancer (high grade cervical dysplasia) has already been demonstrated in a large, prospective, randomized, double blind, placebo-controlled phase II study, HPV-003. Treatment with VGX-3100 resulted in histopathological regression of high grade cervical dysplasia to low grade or no disease, meeting the study's primary endpoint. In addition, the trial demonstrated clearance of the HPV virus in conjunction with regression of cervical lesions, meeting the secondary endpoint. Robust T-cell activity was observed in subjects who received VGX-3100 compared to those who received placebo.
