On October 2, 2018 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported a paper published in a major cancer journal detailed results of a patient with head and neck cancer treated with MEDI0457 achieved a sustained complete response (full remission) on treatment with a subsequent PD-1 checkpoint inhibitor (Press release, Inovio, OCT 2, 2018, View Source [SID1234530271]). In the Inovio-sponsored study of 22 patients with head and neck squamous cell carcinoma the company reported 91% (20/22) showed T cell activity in the blood or tissue. MEDI0457 – formerly called INO-3112 – was in 2015 licensed to MedImmune, the global biologics research and development arm of AstraZeneca. These immune data as well as the financial terms of the license agreement have been previously reported by Inovio.
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Dr. J. Joseph Kim, Inovio’s President and CEO, said, "We are buoyed by the study as it lends support to all of our HPV and oncology programs. These data demonstrated that Inovio’s technology based in MEDI0457 can generate durable HPV16/18 antigen-specific peripheral and tumor immune responses. The study supports our belief that this approach may be used as a complementary strategy to PD-1/PD-L1 inhibition in HPV-associated head and neck and other types of cancer to improve therapeutic outcomes. Inovio is collaborating with MedImmune (w/ MEDI0457) as well as Genentech and Regeneron (w/ INO-5401) in efficacy trials coupling Inovio’s DNA-based cancer immunotherapies with checkpoint inhibitors designed to increase response rates with data expected in 2019."
An article in the most recent edition of Clinical Cancer Research highlights data from an Inovio-sponsored trial that demonstrated that after a cancer progressed a patient was subsequently given a PD-1 checkpoint inhibitor. The patient achieved a complete response, which has sustained for over two years and counting. Increasing evidence suggests that response rates from checkpoint inhibitors 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.
Charu Aggarwal, MD, MPH, the study’s principal investigator and an assistant professor of Hematology-Oncology at the University of Pennsylvania’s Perelman School of Medicine, said, "We wanted to know if this vaccine (MEDI0457) can boost the immune systems of patients with HPV-related head and neck cancer, potentially opening the door for better response rates to other existing therapies, and our findings show that we can."
The article notes that researchers administered four doses of MEDI0457 to 21 patients separated into two different groups. One group received a dose before surgery, followed by three doses after surgery. The second group received four doses following chemotherapy and radiation. Eighteen out of the 21 patients showed elevated T cell activity that lasted at least three months after the final vaccine dose, meaning the immune effect persisted for at least six months from the start of immunotherapy. Five tumors were biopsied both before and after one dose of the vaccine, and there was evidence of T cells infiltrating into tumors and expressing proteins associated with cell killing potential.
"We have not seen that kind of T cell infiltration with just one dose of a vaccine before," Dr. Aggarwal added. "These findings open the door for utilizing targeted immunotherapy approaches against specific cancer-causing targets like HPV."
Overall the characteristics of these immune response data mirrored those previously observed in a Phase 2b clinical study of VGX-3100 for HPV-associated cervical dysplasia. In that study, strong CD8+ T cell immune responses were positively correlated with achievement of primary and secondary efficacy endpoints. VGX-3100, which is currently in global REVEAL 1 Phase 3 trial, is the first therapy to demonstrate that activated killer T cells induced in the body have the power to clear neoplastic lesions as well as the virus which caused the disease.
About MEDI0457 and VGX-3100
MEDI0457 (formerly called INO-3112 (VGX-3100, plus IL-12) which MedImmune in-licensed from Inovio) is under evaluation by MedImmune to treat HPV-associated cancers. Inovio is investigating VGX-3100, a DNA-based immunotherapy for the treatment of HPV-16 and HPV-18 infection and pre-cancerous lesions of the cervix (Phase 3) and vulva (Phase 2). VGX-3100 has the potential to be the first approved treatment for HPV infection of the cervix and the first non-surgical treatment for pre-cancerous cervical lesions. VGX-3100 works by stimulating a specific immune response to HPV-16 and HPV-18, which targets the infection and causes destruction of pre-cancerous cells. In a randomized, double-blind, placebo-controlled phase 2b study in 167 adult women with histologically documented HPV-16/18 cervical HSIL (CIN2/3), treatment with VGX-3100 resulted in a statistically significantly greater decrease in cervical HSIL and clearance of HPV infection vs. placebo. The most common side effect was injection site pain, and no serious adverse events were reported. VGX-3100 utilizes the patient’s own immune system to clear HPV-16 and HPV-18 infection and pre-cancerous lesions without the increased risks associated with surgery, such as loss of reproductive health and negative psychosocial impacts.
About HPV-Caused Head & Neck Cancer
Human papillomavirus (HPV) is the most common sexually transmitted disease in the United States, currently infecting about 79 million Americans. HPV 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. In 2018 an estimated 48,330 persons will get oral cavity or oropharyngeal cancer in the U.S. New cases of head and neck cancer occur nearly three times more often in men as in women. Incidence rates of head and neck cancers have been on the rise, especially HPV-associated oropharyngeal cancer in men, and are expected to continue growing.