December 5, 2014
By Riley McDermid, BioSpace.com Breaking News Editor
San Diego-based cancer researcher OncoSec Medical Inc. said Friday that its new ImmunoPulse melanoma therapy had seen positive data from its Phase II trial, a sign the company says shows that its DNA-based cancer immunotherapies are effective.
OncoSec’s Chief Scientific Officer Robert Pierce, a co-author of the study, presented the data in an abstract at the Melanoma Bridge 2014 conference in Naples, Italy.
OncoSec’s core technology is designed to enhance the local delivery and uptake of DNA IL-12 and other DNA-based immune-targeting agents. So far, clinical studies of ImmunoPulse have been relatively safe and shown some evidence of anti-tumor activity in the treatment of various skin cancers.
OncoSec reported the top-line six-month data from the first Phase II trial of its investigational intratumoral plasmid IL-12 electroporation (pIL-12 EP) monotherapy (ImmunoPulse IL-12) in patients with Stage III and IV metastatic melanoma. The study followed 30 patients with stage III-IV melanoma, each of whom received up to four cycles of pIL-12 EP into superficial cutaneous, subcutaneous and nodal lesions on days one, five and eight of each 12-week cycle.
The company said tumor responses were evaluated using modified RECIST criteria for cutaneous lesions. The primary endpoint of the study was best overall response rate (bORR) by modified RECIST. In the 29 response-evaluable patients, bORR was 31 percent, with 14 percent of patients achieving a complete response (CR). Perhaps more importantly, 50 percent of patients saw regression of at least one non-injected, non-electroporated lesion.
“Along with the Phase I long-term survival analysis presented yesterday, these data continue to support the use of pIL-12 EP as a treatment for metastatic melanoma,” said Mai Le, chief medical officer, in a statement. “Importantly, our observation that non-treated lesions regress in approximately half of the patients suggests that local, intratumoral pIL-12 EP successfully induces a more global anti-tumor immune-mediated response.”
OncoSec said the main side effect was “transient Grade 1/2 pain” at the treatment site, experienced by 87 percent of patients. It said that pain was “directly associated with the procedure,” with only median duration of one minute. Only one Grade 3 adverse event of pain was reported.
After the study, OncoSec found that analysis of tissue samples from patients treated with pIL-12 EP showed a gene expression pattern consistent with generation of an inflammatory response with increased CD8+ TILs (tumor-infiltrating lymphocytes) and the induction of key immune co-stimulatory molecules. The company said that means that it has corroborated the results of preclinical experiments testing pIL-12 EP in the B16.F10 mouse melanoma model, which also indicated the presence of CD8+ TILs (tumor-infiltrating lymphocytes) and the induction of adaptive resistance mechanisms in distant tumors.
“We are pleased to see such good concordance between our findings from patient biopsy samples and the B16.F10 mouse model,” said Pierce. “This gives us confidence that we can use this experimental model to deepen our understanding of how ImmunoPulse re-programs the immune system to drive a systemic anti-cancer immune response. Taken together, these clinical and preclinical data provide further evidence for combining this approach with checkpoint inhibitors such as anti-PD-1.”
