INO-3112 immunotherapy for head & neck cancer

Phase II

  • Head & neck cancer



Phase I/II study progressing

cervical dysplasia stain

MedImmune acquired the rights to develop Inovio’s INO-3112 (VGX-3100 plus DNA-based immune activator encoded for IL-12) DNA immunotherapy targeting the E6 and E7 oncogenes of human papillomavirus (HPV) types 16 and 18 against HPV-caused cancers. This immunotherapy enables the body to produce E6 and E7 antigens in order to induce a stronger targeted immune response against HPV-associated diseases such as head and neck cancer. This DNA immunotherapy will be delivered intramuscularly followed by electroporation using our CELLECTRA® delivery device. MedImmune expects to evaluate INO-3112 in combination with multiple immune-oncology molecules.

Development Status
Following positive phase I results with VGX-3100, Inovio’s DNA immunotherapy designed to treat HPV-caused precancers and cancers, Inovio advanced INO-3112 into phase I/IIa clinical studies to treat HPV-caused head and neck cancer in the second quarter of 2014. This study will now be part of MedImmune’s development plans.

Disease State
HPV now plays a major role in the development of head/neck cancers. In fact, the CDC estimates that more than 11,726 new cases of HPV-caused oropharyngeal cancers are diagnosed each year in the United States and over 7,922 deaths occur annually (in the US).  An additional 13,896 cases are diagnosed each year in the five major markets of the European Union. These statistics are based on cancers in the oropharynx only and do not include other head and neck cancers caused by HPV, including cancers of the oral cavity, oropharynx, nose/nasal passages and larynx.

Clinical Trials

Clinical Trials

INO-3112 head & neck cancer immunotherapy

In 2Q 2014, Inovio initiated a phase I/IIa clinical trial to evaluate safety, immunogenicity and clinical responses of INO-3112 to treat 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 (INO-9012).

In this open-label study, 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 tumor. 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 a combination of 6 mg of VGX-3100 and 1 mg of DNA-based IL-12 (designated INO-9012) delivered together intramuscularly with Inovio’s CELLECTRA® electroporation delivery device.

In addition to assessing safety, this study will analyze T cell immune responses (cellular immune responses) to INO-3112. Pre- and post-immunotherapy tumor tissue will be analyzed to evaluate infiltration of T cells into the tumor and tumor bed. Clinical responses characterized by anti-tumor effects (tumor shrinkage or regression), 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 centers, and led by principal investigator Charu Aggarwal, MD, MPH, assistant professor of medicine in the division of hematology-oncology at the PSOM and ACC.

Study Data

Study Data

INO-3112 SynCon® head & neck cancer immunotherapy

INO-3112 generated strong CD8+ T cell responses in 3 of 4 patients with head and neck cancer associated with human papillomavirus (HPV) types 16 and 18.

These positive results represent the first study and first report of T cell immune responses generated in cancer patients after treatment with an Inovio DNA immunotherapy. The magnitude and characteristics of these interim immune response data mirror immune responses previously observed in human studies of VGX-3100 for HPV-associated cervical dysplasia; in a placebo-controlled phase II study, strong T cell immune responses were positively correlated with achievement of primary and secondary efficacy endpoints.

More Information

More Information

Head & neck cancer caused by HPV

Head and neck cancers associated with HPV usually begin in the squamous cells that line the mucosal surface of the head and neck and include cancer of the oral cavity, oropharynx, nose/nasal passages and larynx. These cancers account for nearly 3 percent of all cancers in the United States and are twice as prevalent in men as in women. Head and neck cancers are also more common in people over the age of 50. 

Incidence rates of HPV-caused head and neck cancers have been on the rise in many countries, especially HPV-associated oropharyngeal cancer in men. While nearly 75% of head and neck cancers are caused by tobacco and alcohol use, roughly 63% of oropharyngeal cancer is caused by HPV (predominantly HPV type 16).

The oropharynx includes the middle part of the throat, the base of the tongue, and the tonsils. 95% of HPV-caused oropharyngeal cancer is attributable to HPV types 16 and 18. The estimated prevalence of HPV-caused oropharyngeal cancer in the U.S. in 2012 was 211,827. Overall, the incidence of HPV-caused oropharyngeal cancer has increased significantly within the last 20 years and is expected to continue growing. By 2020, scientists estimate that HPV will cause more cases of oropharyngeal cancer than cervical cancer. In addition, researchers believe that by 2025 HPV will be the causative factor of 90% of all head/neck cancers.

Treatment for HPV-caused head and neck cancers vary depending on the location of the tumor and the stage of cancer, however, treatment options generally include surgery, radiation therapy, chemotherapy, or targeted therapy. These forms of treatment have negative side effects. Surgery for head and neck cancers may change or diminish a patient’s ability to chew, swallow, or talk and cause swelling in the face and neck. Radiation therapy can lead to sores in the mouth, difficulty swallowing, a change in taste, and nausea. In addition, some patients need to undergo reconstructive and plastic surgery to rebuild bones or tissues, or undergo speech therapy after they have received their initial cancer treatments.