On May 10, 2017 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported MedImmune, AstraZeneca’s global biologics research and development arm, will start a new clinical trial investigating the combination of MEDI0457, an immunotherapy designed to generate antigen specific killer T cell responses targeting HPV-associated tumors, and durvalumab, an investigational PD-L1 checkpoint inhibitor (Press release, Inovio, MAY 10, 2017, View Source;Neck-Cancer/default.aspx [SID1234518975]). The combination trial will enroll patients with metastatic HPV-associated squamous cell carcinoma of the head & neck (SCCHN) with persistent or recurrent disease after chemotherapy treatment. Schedule your 30 min Free 1stOncology Demo! The open-label study is designed to evaluate the safety and efficacy of the combination therapy in approximately 50 subjects at multiple U.S. sites. Subjects will receive multiple doses of MEDI0457 (previously known as INO-3112) and durvalumab. The primary endpoints of the study are safety and objective response rate. The study will also evaluate immunological impact, progression-free survival and overall survival.
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Dr. J. Joseph Kim, Inovio’s President and CEO, said, "This study marks a significant moment for Inovio as we transition into a late-stage biotechnology company. MedImmune is investigating the possibility of elevating the response rate of checkpoint inhibitors by using durvalumab in combination with a DNA plasmid vaccine originally from Inovio which has shown the ability to generate killer T cells. I’m a strong believer in this combination regimen strategy against cancer: utilize Inovio’s cancer vaccine to generate significant levels of antigen-specific killer T cells, have them infiltrate into tumors — or what is being referenced as turning a tumor from "cold" to "hot" — then suppress the cancer cells’ defensive mechanisms utilizing a checkpoint inhibitor. We think that powerful combination can be effective in treating multiple tumors going forward."
Increasing evidence suggests that response rates from checkpoint inhibitors such as MedImmune’s durvalumab can be enhanced when used in combination with cancer vaccines like MEDI0457 that generate tumor-specific T cells. Interim data from a MEDI0457 monotherapy study of head and neck cancer patients demonstrated that MEDI0457 generated robust HPV16/18 specific CD8+ T cell responses in peripheral blood and increased CD8+ T cell infiltration in resected tumor tissue samples.
In 2015, MedImmune acquired exclusive rights to Inovio’s INO-3112 immunotherapy for all HPV-associated cancers. MedImmune provided an upfront payment of $27.5 million to Inovio as well as potential future payments upon reaching development and commercial milestones totaling up to $700 million. MedImmune will fund all development costs. Inovio is entitled to receive up to double-digit tiered royalties on INO-3112 product sales.
About HPV-associated Head & Neck Cancer
Head and neck cancer is the sixth most common cancer worldwide. Human papillomavirus (HPV), the most common sexually transmitted disease in the US, is known to play a major role in the development of head and neck cancers, which include cancers of the oral cavity, oropharynx, nose/nasal passages and larynx. New cases of HPV-associated squamous cell carcinoma of the head & neck (SCCHN) are growing fastest in developed countries like the US. There are approximately 16,000 new cases of HPV-associated SCCHN per year in the US alone. In contrast, the rate of smoking and alcohol-related SCCHN has been steadily declining. Men are four times more likely than women to be diagnosed with this disease. Patients with HPV-associated SCCHN tend to be diagnosed at a younger age than those with smoking and alcohol related disease.
Head and neck cancers are currently treated by surgical removal of the cancer and lymph nodes, often followed by radiation and chemotherapy based on the extent of the disease. While patients may achieve good long-term survival, standard treatments can change their physical appearance and are associated with significant short and long-term toxicities which may interfere with salivary gland function, taste, smell, and the ability to swallow. The biology and natural history of oropharyngeal HPV infection and the best clinical management of patients with HPV-associated SCCHN are not well understood.
About MEDI0457 (INO-3112)
Inovio’s DNA-based immunotherapies help the immune system activate disease-specific killer T cells to fight a targeted disease. INO-3112 targets disease associated with the high-risk HPV types 16 and 18, which are responsible for over 70% of cervical pre-cancers and cancers and 60% of head and neck cancers. INO-3112 combines Inovio’s VGX-3100, its immunotherapy targeting HPV-associated diseases, with its DNA-based immune activator encoding IL-12.
About Durvalumab
Durvalumab, previously known as MEDI4736, a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumour’s immune-evading tactics and inducing an immune response. Additional clinical trials are ongoing to investigate durvalumab as monotherapy or in combination with tremelimumab in non-small cell lung cancer, head and neck squamous cell carcinoma, bladder, hepatocellular carcinoma and blood cancers.