Inovio Pharmaceuticals has announced 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.

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.

The open-label study is designed to evaluate the safety and efficacy of the combination therapy in approximately 50 subjects at multiple US 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.

Dr. J. Joseph Kim, Inovio's president and chief executive officer, 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.