Inovio Pharmaceuticals, Inc has initiated a phase I/IIa clinical trial to evaluate safety, immunogenicity and clinical responses of its immunotherapy product, INO-3112, in treating human papillomavirus (HPV)- associated head and neck 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 randomised phase II efficacy trial for the treatment of high grade cervical dysplasia (pre-cancer).

In a phase I trial of VGX-3100, Inovio demonstrated that this immunotherapy produced high levels of durable T cell immune responses, notably CD8+ "killer" T cells, in 78 per cent of all patients in the study. These CD8+ T cells showed the functional ability to kill target cells displaying the E6 and E7 antigens. In preclinical animal models, Inovio's HPV immunotherapy demonstrated 100 per cent.protection against HPV E6 and E7-expressing tumours and prevented or delayed the growth of such tumours. The proprietary IL-12 immune activator, 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 designed to increase the generation of HPV-specific CD8+ T cells for the treatment of HPV-related cancer.

In this open-label study, called HPV-005, up to twenty adults with HPV-positive head and neck squamous cell carcinoma (HNSCC) will be treated with INO-3112 and followed for safety, immune and clinical responses. In one part of the study, up to ten patients will be treated with INO-3112 before and after resection of their tumour. In the second part of the study, up to ten patients will be treated with INO-3112 after completion of chemotherapy and radiation therapy. Each INO-3112 treatment will be administered using Inovio's Cellectra delivery system.

In addition to assessing safety, this study will analyse T cell immune responses to INO-3112. Pre- and post-immunotherapy tumour tissue will be analysed to evaluate infiltration of T cells into the tumour and tumour bed. Clinical responses characterised by anti-tumour effects, using RECIST criteria, and progression free survival will also be measured.

The study will be conducted at the Abramson Cancer Center (ACC) in the Perelman School of Medicine (PSOM) at the University of Pennsylvania, one of the world's premier cancer treatment centre, and led by principal investigator Charu Aggarwal, MD, MPH, assistant professor of medicine in the division of hematology-oncology at the PSOM and ACC.  

Dr. J. Joseph Kim, Inovio's president and chief executive officer, said, "Initiating this head and neck cancer study is just the tip of the iceberg in our oncology immune therapy development plans. Onco-immunotherapy is all about T cells the very thing which our products have been shown to stimulate extremely well. We look forward to our upcoming unblinded cervical dysplasia phase II study data on efficacy and T cell responses this summer."  

"We will also launch additional cancer clinical studies to further characterise and expand the potential of our DNA immune therapy products and immune activators with their potent abilities to generate and activate the highest levels of antigen-specific killer T cells. These include trials for INO-5150 for prostate cancer with our pharmaceutical partner in Q3 and INO-1400, our immunotherapy encoded for hTERT in breast, lung and pancreatic cancer patients later this year. Our goal is to have the best and most extensive pipeline of active cancer immunotherapies with the potential to seek out and destroy cancer cells," said Dr. Kim.

Human papillomavirus (HPV) is the most common sexually transmitted disease in the United States, infecting 79 million Americans. HPV infection may lead to cervical dysplasia and cancer as well as cancers of the anogenital tract. HPV-caused head and neck cancer is the fastest growing cancer in men and is expected to overtake the incidence of HPV-caused cervical cancers by the end of this decade. If proven effective, INO-3112 could augment current therapeutic approaches to head and neck cancer. Today's therapy for oropharyngeal (head & neck) cancer is a combination of chemotherapy, radiation and surgical resection. The treatments have many potential side effects, including damage to the throat, which can hinder the ability to speak and swallow.

Inovio's lead product, VGX-3100, is a DNA-based immunotherapy for precancers and cancers caused by HPV. This product, without an immune activator, is currently in a randomised, double-blind phase II trial evaluating its efficacy and immune responses against HPV-caused cervical dysplasia. INO-3112 combines this immunotherapy with a DNA-based IL-12 immune activator to further boost the targeted immune response against head and neck cancer, cervical cancer and other cancers.