MEDI0457 (previously called INO-3112) is an investigational immunotherapy being developed to treat human papillomavirus (HPV)-positive cervical cancer and head and neck cancer.

MEDI0457 was originally developed by Inovio, but MedImmune, which is part of AstraZeneca, acquired exclusive rights to the drug in August 2015.

How MEDI0457 works

The majority of cervical cancers, among various other cancer types, can be caused by HPV. MEDI0457 targets the E6 and E7 oncogenes, which are genes that have the potential to cause cancer, expressed by HPV types 16 and 18.

MEDI0457 is a DNA-based cancer vaccine with two main components produced using Inovio’s proprietary SynCon technology. Those components are VGX-3100, a DNA plasmid containing modified sequences for E6 and E7, and INO-9012, a DNA plasmid containing the immune activator IL-12. Plasmids are pieces of circular DNA that contain the sequences necessary to promote the expression of a certain gene.

MEDI0457 is injected into the patient’s muscle and enters the cells after electroporation treatment carried out by Inovio’s Cellectra delivery device. Electroporation is the application of a small electrical pulse. When E6 and E7 are expressed from VGX-3100, the immune system recognizes these proteins as antigens, or foreign substances associated with an infection or disease. This triggers the production of cytotoxic T lymphocytes (CTLs), or “killer” T-cells. CTLs are a type of immune cell that can identify and destroy cells expressing a particular antigen, in this case, the HPV-infected tumor cells. The expression of IL-12 will boost the immune response produced by VGX-3100 as it stimulates the production of CTLs, increasing the potential for tumor cell death.

MEDI0457 in clinical trials

Inovio is running a Phase 1/2a clinical trial (NCT02163057) called HPV-005 to assess MEDI0457 in up to 20 HPV-positive head and neck squamous cell carcinoma (HNSCC) patients who have either received prior surgery or chemoradiation treatment.

In November 2016, Inovio presented preliminary results at the Annual Meeting of the Society for Immunotherapy of Cancer (SITC) showing that MEDI0457 successfully generated a targeted immune response in four of the five analyzed HNSCC patients. These four patients were still disease-free at the point of last follow-up, which ranged from nine to 24 months. Cancer progressed in the fifth patient, who did not have a significant immune response to MEDI0457.

Inovio is also carrying out an open-label Phase 1/2a clinical trial (NCT02172911), called HPV-004, in 30 women with inoperable cervical cancer at three sites across the U.S.

MedImmune is now recruiting up to an estimated 50 patients with HPV-positive HNSCC for a Phase 1/2 clinical trial (NCT03162224) to assess the safety and anti-tumor activity of MEDI0457 in combination with their immune checkpoint inhibitor drug Imfinzi (durvalumab). The trial is taking place at three sites across the U.S.


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