Inovio Pharmaceuticals Inc. announced it has initiated a Phase 1/2a clinical trial to evaluate safety, immunogenicity, clinical responses and disease-free survival of its DNA immunotherapy product, INO-3112, in treating human papillomavirus (HPV)-associated cervical cancer. INO-3112 is a combination of Inovio’s lead active immunotherapy product, VGX-3100, and its proprietary immune activator expressing interleukin-12 (IL-12). VGX-3100 is currently being evaluated in a randomized Phase 2 efficacy trial for the treatment of high grade cervical dysplasia (pre-cancer).This open-label study, called HPV-004, will evaluate INO-3112 in 20 female subjects with inoperable invasive cervical cancer. Subjects will receive four treatments of INO-3112 every four weeks after completion of a standard chemoradiation regimen. Each INO-3112 treatment will be a combination of 6 mg of VGX-3100 and 1 mg of DNA-based IL-12 delivered together intramuscularly with the Cellectra delivery system.
As an exploratory analysis, the study team will evaluate clinical responses at the tumor site (tumor shrinkage or regression) and assess disease-free survival and disease recurrence up to 12 months after the initial immunotherapy with Inovio’s INO-3112. Cellular (T cell) immune responses will be analyzed pre- and post-immunotherapy in the tumor tissue as well as in the bloodstream.
In a Phase 1 trial of VGX-3100, Inovio demonstrated that this HPV immunotherapy produced high levels of durable T cell immune responses, notably CD8+ T cells, in 78% of all patients. These CD8+ T cells showed the functional ability to kill target cells displaying the antigens E6 and E7. In preclinical animal models, this DNA-based immunotherapy demonstrated 100% protection against HPV E6 and E7-expressing tumors and prevented or delayed the growth of such tumors. The proprietary IL-12 immune activator, called INO-9012, was previously shown to enhance antigen-specific CD4+ and CD8+ T cell immune responses to Inovio’s Pennvax HIV DNA vaccine in a clinical trial. Inclusion of this DNA-based immune activator in INO-3112 is intended to further strengthen the generation of HPV-specific CD8+ T cells to treat HPV-caused cancer.
This cervical cancer study is being conducted at the University of Chicago Medical Center and at the Comprehensive Cancer Center at Silver Cross, Ill, where Dr. Yasmin Hasan, director of Gynecological Radiation Oncology and Brachytherapy, is the principal investigator.
Dr. J. Joseph Kim, Inovio’s president and CEO, said, “This study extends our pioneering HPV immune-based treatment into cervical cancer, the No. 2 cancer killer of women in the world. Our goal is to fully address the post-HPV infection immune therapeutics markets, targeting not only HPV-related cervical pre-cancer but also cervical cancer as well as head and neck and anogenital cancers.”
“Cancer immunotherapy is focused on generating cancer fighting T cells and freeing them to attack targeted cancer cells. Inovio has demonstrated that its therapies mobilize more antigen-specific T cells than any other product on the market or in development. We look forward to reporting unblinded cervical dysplasia Phase 2 study data on efficacy and T cell responses by the end of July. Our aim is to have the best and most extensive pipeline of active cancer immunotherapies with the potential to seek out and destroy cancer cells,” said Kim.
Date: June 23, 2014
Source: Inovio Pharmaceuticals
