INO-3112 immunotherapy for cervical cancer
MilestonePhase I/II study progressing
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. Cervical cancer is one of the many diseases caused by HPV. 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 cervical cancer. This 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.
Following positive phase II results with VGX-3100, Inovio’s DNA immune therapy for HPV-caused precancers and cancers, Inovio advanced INO-3112 into phase I/IIa clinical studies to treat HPV-caused cervical cancer in the second quarter of 2014. This study will now be part of MedImmune’s development plans.
Cervical cancer currently affects approximately 530,000 women worldwide and results in over 275,000 deaths annually. Though there are currently two approved vaccines (Gardasil® and Cervarix®) to prevent HPV-caused cervical cancer, only 38% of teenagers who qualify for immunization actually receive all three required HPV vaccine doses. Without consistent HPV vaccination or improvements in screening and treatments, deaths resulting from cervical cancer are expected to rise by approximately 25% over the next 10 years. As a result, there is a significant need for an effective therapeutic vaccine to treat cervical cancer caused by the human papilloma virus (HPV).
INO-3112 cervical cancer immunotherapy
In 2Q 2014, Inovio initiated a phase I/IIa clinical trial to evaluate safety, immunogenicity, clinical responses, disease-free survival and progression free survival of its DNA immunotherapy product, INO-3112, in treating human papillomavirus (HPV)-associated cervical cancer. INO-3112 is a combination of Inovio's lead active immunotherapy product, VGX-3100, and its proprietary immune activator expressing interleukin-12 (IL-12).
This open-label study, HPV-004, is evaluating INO-3112 in 30 female subjects with stage IB-IVB inoperable invasive cervical cancer who have completed treatment with standard chemoradiation therapy with curative intent (cohort 1) or in women with persistent and/or recurrent inoperable cervical cancer following salvage therapy (cohort 2). Study patients will receive four treatments of INO-3112 every four weeks. 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.
As an exploratory analysis, the study team will evaluate clinical responses at the tumor site (tumor shrinkage or regression), assess disease-free survival and disease recurrence up to 12 months after the initial immunization with INO-3112 and progression free survival at 18 months after the initial immunization with INO-3112. Cellular (T cell) immune responses will be analyzed pre- and post-immunization in the tumor tissue as well as in the bloodstream.
This cervical cancer study is being conducted at the University of Chicago Medical Center and at the Comprehensive Cancer Center at Silver Cross, IL, where Dr. Yasmin Hasan, Director of Gynecological Radiation Oncology and Brachytherapy, is the principal investigator. This study is being conducted in collaboration with MedImmune.
INO-3112 SynCon® cervical cancer immunotherapy
There is no study data for cervical cancer at this time, however, 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.
Cervical cancer caused by HPV
Cervical cancer is the most commonly occurring cancer among women in developing countries and is the second most commonly occurring cancer amongst women worldwide. In the United States, it is estimated that 11,818 women are diagnosed with cervical cancer each year. According to the World Health Organization, cervical cancer is 100% attributable to human papilloma virus (HPV) infection and HPV DNA has been found in 99.7% of tumor biopsy specimens. Although there are over 150 genotypes for HPV, 40 types are associated with the genital area. Of these, 70% of cervical cancer cases are caused by human papillomavirus (HPV) types 16 & 18.
Two FDA-approved preventive vaccines are designed to generate immunity and protect against HPV infection in non-infected individuals, however only 38% of teenagers who qualify for immunization actually receive all three required HPV vaccine doses. In addition, once a person has an established HPV infection, these vaccines are not able to prevent the development of HPV into cervical cancer. Without consistent HPV vaccination or improvements in screening and treatments, current incidence trends suggest that the incidence of cervical cancer could rise from roughly 530,000 cases per year to approximately 1 million cases per year in 2050.
There are three types of standard treatment used for patients with cervical cancer including surgery, radiation therapy, and chemotherapy. Surgery can be radical, removing the cervix, uterus, upper part of the vagina, ovaries, and/or fallopian tubes, or localized, using a laser, electrical currents, or cryotherapy (freezing mechanism) to remove cancerous tissue.
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