Inovio Pharmaceuticals, has initiated a phase I trial of its hTERT DNA immunotherapy (INO-1400) alone or in combination with Inovio's IL-12 immune activator (INO-9012) in adults with breast, lung, or pancreatic cancer at high risk of relapse after surgery and other cancer treatments. Because high levels of hTERT (human telomerase reverse transcriptase) expression are found in 85 per cent  of human cancers, Inovio's cancer candidate holds the potential as a broad spectrum cancer therapeutic.

A previously published study of this product showed that administration in monkeys, whose TERT is 96 per cent  similar to human TERT, generated strong and broad TERT-specific immune responses and demonstrated the potential to eliminate tumour cells. Mice immunised with Inovio's DNA immunotherapy experienced delayed tumour growth, tumour shrinkage, and longer overall survival compared with non-immunised mice.

This human trial is an open label, dose escalation study in subjects with breast, lung, or pancreatic cancer at high risk of relapse after surgery and other treatments including chemotherapy and radiation. Approximately 54 subjects will be enrolled into one of six treatment groups and receive INO-1400 alone or in combination with INO-9012, Inovio's immune activator. The study will be conducted at the University of Pennsylvania's Abramson Cancer Center, which will fund all site-specific clinical study costs.

Lung, breast, and pancreatic cancer mortality rates are ranked first, third, and fourth, respectively, among cancer types in the United States, despite improvement in detection and treatment. In each of these three cancer types, significant numbers of patients undergo surgical resection and adjuvant therapy with an attempt at cure, but only a fraction remain in remission. This study will evaluate Inovio's novel immunotherapy with the ultimate goal of reducing the risk of relapse in these patients.

Robert Vonderheide, MD, DPhil, said, "The next great wave of oncology advancements will be treatments which empower the patient's own immune system to seek and destroy cancer. In this study we will evaluate a new immunotherapy targeting the hTERT gene found in numerous cancers."  Dr. Vonderheide is Professor of Medicine; Hanna Wise Professor in Cancer Research; Associate Director for Translational Research, Abramson Cancer Center; Vice Chief for Research, Hematology-Oncology Division, Department of Medicine.

Dr. J. Joseph Kim, president and chief executive officer, said, "We are enthusiastic about the potential use of INO-1400 cancer immunotherapy in multiple major cancers, given that hTERT is expressed in the vast majority of cancer types yet is rare in normal cells. INO-1400 therapy adds to Inovio's growing oncology franchise led by our phase III candidate, VGX-3100, for treating HPV-related pre-cancers and cancers."  

The primary objective of this study is to evaluate the safety and tolerability of INO-1400 alone or in combination with INO-9012, delivered intramuscularly in subjects with high-risk breast, lung, or pancreatic cancer with no evidence of disease after surgery and adjuvant therapy. The secondary objectives are to evaluate cellular and humoral immune responses, measure time to disease progression, and evaluate immunotherapy-induced changes in subjects.

Inovio's DNA-based immunotherapy technology uniquely activates and multiplies in the body highly potent antigen-specific killer T cells targeting a specific cancer. The company's technology provides the most natural interaction with the immune system next to an actual infection, therefore the activated therapeutic response remains controlled by the immune system and has to date not triggered unwanted inflammatory responses. These are ideal characteristics of an immuno-oncology product. The immune system uses the same weapons to fight precancerous and cancerous cells – sometimes the immune system simply requires assistance to mount an effective immune response.  Inovio achieved an industry first with clinically significant efficacy shown with its VGX-3100 HPV immunotherapy in a phase II study of cervical precancer. Inovio is now advancing multiple clinical and R&D stage active immunotherapies with the potential to address the full spectrum of precancers and cancers.