Data from previous Phase I study identifies that presence of novel antigens plus DNA IL-12 delivered using electroporation achieves stabilization and regression of treated and distant untreated melanoma tumors
SAN DIEGO, CA, June 7, 2011 — OncoSec Medical Incorporated (OTCBB: ONCS), which is developing its advanced-stage ElectroOncology therapies to treat solid tumor cancers, announced today that additional evaluation of a previous Phase I trial provided further evidence that a DNA plasmid encoded to produce IL-12 delivered by electroporation into melanoma lesions induces responses to known and novel antigens, resulting in regression of local treated lesions as well as distant untreated lesions. The results were presented by Dr. Adil Daud, principal investigator of the study, at the ASCO 2011 Annual Meeting.
In this Phase I trial, the experimental regimen was safe and well tolerated, with minimal systemic toxicity. Local treated lesions were biopsied and showed that 76% of all samples had at least 20% necrosis of the tumor, with 34% of those lesions showing 100% necrosis (clearance of the tumor). Furthermore, patients with additional tumors beyond the treated tumor were followed to determine regression of distant untreated lesions. Results demonstrated that 10 (53%) of 19 patients with distant untreated lesions showed at least stable disease or objective (partial or complete) regression. In addition, 15% of these patients demonstrated 100% clearance of distant, untreated metastatic melanoma tumors; by comparison, only 0.25% of such tumors would normally be expected to clear on their own if left untreated. The observed tumor regression of untreated lesions suggested a systemic immune response to the localized treatment. The data demonstrated a dose-dependent increase in intratumoral IL-12 protein expression and concomitant increases in intratumoral IFN-gamma. In addition, this study showed that electroporated tumors contained CD4+ and CD8+ lymphocytic infiltrates in the treated lesions, further validating the ability of DNA IL-12 to up-regulate adaptive and innate immunity.
Following this Phase I study, the researchers conducted additional analysis into the ability of DNA IL-12 to induce a systemic immune response against distant metastatic lesions and more importantly to potentially identify blood markers that can be used to predict if a specific sub-set of patients is more likely to respond to DNA IL-12. Evaluable patients were categorized by tumor response (complete, partial response, stable disease or disease progression) and the researchers analyzed blood samples obtained at weeks 1, 4 and 6. Among numerous antigens tested and identified, two candidates, namely epidermally-localized protein (4.2-fold, p = 0.008) and a testis-restricted antigen (3.0-fold, p = 0.037), were present in subjects who displayed a significant differential in tumor response versus those that were non-responders. These results indicate that blood markers may exist that can predict whether patients will respond to treatment with DNA IL-12 with electroporation, further adding to the selective potential of this treatment.
Dr. Adil Daud, Clinical Professor of Medicine at the University of California, San Francisco, who led the exploratory study, said, “This first-in-man study demonstrated that local intratumoral electroporation of DNA IL-12 in melanoma induces systemic immune responses that can stabilize or cause regression of not only local treated but also distant untreated metastatic melanoma tumors. We are also pleased with this new analysis indicating that measurable blood markers may be useful in selecting patients more likely to respond to this treatment. These results provide significant encouragement that DNA-IL12 delivered with electroporation may represent an important new treatment against challenging cancers such as melanoma.”
Punit Dhillon, OncoSec’s President and CEO, said, “Melanoma is an aggressive skin cancer, and metastatic melanoma is generally lethal. Just stabilizing this disease is an accomplishment, but we are very enthusiastic about the results of this Phase I study showing regression of treated and untreated tumors, as well as the insights into potential new markers. We look forward to launching OncoSec’s planned three Phase II skin cancer trials this summer. Our goal is to further validate these results and show the breakthrough nature of this tissue-sparing, tumor killing drug/device cancer therapy.”
This data relates to OncoSec’s ElectroImmunotherapy using a DNA plasmid coding for IL-12 that is delivered using electroporation. Electroporation enables significant cellular uptake of the DNA IL-12, which then instructs the cells to produce the protein IL-12. IL-12 stimulates the release of cytotoxic T-cells, natural killer (NK) cells, and IFN-gamma, which in conjunction up-regulate the production of CD4+ and CD8+ lymphocytic infiltrates, resulting in an immuno-reaction against cancers that leads to cancer cell death.
OncoSec has announced that it will initiate three Phase II clinical trials in the next several months to assess its ElectroImmunotherapy technology in patients with melanoma, Merkel cell carcinoma and cutaneous T-cell lymphoma. If OncoSec’s Phase II trials further validate the initial Phase I evidence, the DNA-based IL-12 ElectroImmunotherapy platform would represent an important advancement in the treatment of both local and metastatic cancers.
The incidence of many common cancers is falling, but the incidence of melanoma continues to rise at a rate faster than that of any of the seven most common cancers. Between 1992 and 2004, melanoma incidence increased 45 percent, or 3.1 percent annually. An estimated 68,000 new cases of melanoma were diagnosed in the U.S. in 2010 – with nearly 8,700 resulting in death. Approximately 75 percent of skin cancer deaths are from melanoma. In 2004, the most recent figures available, the total direct medical cost associated with the treatment of skin cancer in the U.S. was $1.5 billion. Currently there are few treatment options for metastatic melanoma because of the aggressive nature of the disease. Current treatment approaches are associated with high morbidity and only marginal improvements in overall survival.
About OncoSec Medical Inc.
Oncosec Medical (OTCBB: ONCS) develops novel ElectroOncology therapies that combine its proprietary electroporation delivery technology with a chemotherapeutic or novel DNA-based immunotherapeutics. Targeted local delivery of these agents is designed to achieve selective destruction of cancerous tumors while sparing healthy normal tissue, resulting in improved functional, cosmetic and quality of life outcomes. These therapies have achieved validating safety and efficacy data in early and late stage clinical studies of over 400 cancer patients. OncoSec’s clinical programs include three Phase II clinical trials. More information is available at www.oncosec.com.