INO-9012 is an investigational DNA-based cancer vaccine being developed by Inovio. The treatment is currently being studied in combination with other experimental therapies for the treatment of many types of cancers and also viral infections.
How INO-9012 works
INO-9012 consists of a DNA molecule (plasmid) that encodes for interleukin-12 (IL-12), which is an inflammatory molecule naturally produced by various immune cells (such as macrophages and dendritic cells) in response to foreign invasion.
INO-9012 is administered into the muscle of the patient by electroporation, a technique that uses electric shocks to introduce DNA into cells. Upon administration, the DNA is read by the patient’s cells to produce IL-12, which activates the immune system by promoting the growth of specialized immune cells called T-cells. T-cells then stimulate the production of another cell-signaling molecule called interferon-gamma (IFN-γ), activating other types of immune cells such as natural killer cells (NK cells) and killer T-cells against tumor cells or virus-infected cells. That results in the inhibition of their growth and their killing.
INO-9012 in clinical trials
Head and neck cancer caused by the human papillomavirus (HPV)
The safety, tolerability, and immunogenicity (ability to trigger an immune response) of INO-9012 is being tested in combination with VGX-3100 in an open-label, Phase 1/2a study (NCT02163057) in patients with HPV-associated head and neck squamous cell cancer.
VGX-3100 is another investigational therapy containing DNA plasmids that encode for E6 and E7 proteins of the HPV subtypes 16 and 18. The combination is called INO-3112.
An interim analysis of the trial results showed that INO-3112 induced a robust immune response involving killer T-cells against the HPV-specific antigens in the patients.
Cervical cancer caused by HPV
An open-label, Phase 1/2a study (NCT02172911) aims to evaluate the safety, tolerability, and immunogenicity of INO-9012 in combination with VGX-3100 (INO-3112) in women with HPV-associated cervical carcinoma. The study is expected to be completed in 2018.
Aerodigestive cancer caused by HPV
An open-label, Phase 1 study (NCT02241369) is currently recruiting participants to evaluate the safety, tolerability, and immunogenicity of INO-9012 in combination with INO-3106 (which contains DNA plasmids that encode for E6 and E7 proteins of the HPV subtype 6) in patients with HPV6-associated aerodigestive precancerous lesions and malignancies.
Multiple solid tumors
An open-label, Phase 1 study (NCT02960594) is recruiting patients in the U.S. with high-risk solid tumors with no evidence of disease after surgery and standard therapy. The study intends to evaluate the safety, tolerability, and immunogenicity of INO-9012 in combination with INO-1400 (which contains a DNA plasmid encoding for an altered enzyme called human telomerase reverse transcriptase – hTERT) in patients with cancers that express hTERT (breast, lung, pancreatic, head and neck, ovarian,colorectal, gastric, esophageal, or hepatocellular cancer).
An open-label, Phase 1 study (NCT02514213) aims to evaluate the safety, tolerability, and immunogenicity of INO-9012 in combination with INO-5150 (which contains DNA plasmids encoding for prostate-specific antigen – PSA and prostatic-specific membrane antigen – PSMA) in men with prostate cancer.
Advanced bladder cancer
Inovio is collaborating with Genentech to start a clinical trial that will evaluate the safety and effectiveness of INO-9012 and INO-5401, which encodes for three cancer antigens (Wilms tumor 1 or WT1, hTERT, and PSMA) in combination with the immune checkpoint inhibitor Tecentriq (atezolizumab) in patients with advanced bladder cancer. Tecentriq is a monoclonal antibody that blocks the interaction of a ligand-receptor pair called PD-L1 and PD-1, enabling T-cell activation.
Inovio also has agreed to work with Regeneron Pharmaceuticals in a Phase 1b/2a clinical trial that will evaluate INO-9012 in combination with REGN2810 (another PD-1 inhibitor) and INO-5401 in patients with newly diagnosed glioblastoma multiforme (GBM), an aggressive type of brain cancer.
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