“The first patient has been dosed in a phase I/II open-label, multicenter trial investigating a novel immunotherapy combination in patients with newly diagnosed glioblastoma (GBM). Fifty patients have been accrued in the trial, as of May 31, 2018, which will be conducted at 25 sites across the nation.
“This study aims to investigate the efficacy of INO-5401, a T-cell activating immunotherapy agent encoding multiple antigens in GBM, and INO-9012, an immune activator encoding IL-12, in combination with the PD-1 inhibitor cemiplimab (REGN2810).”
“Immunopulse IL-12 monotherapy and in combination with pembrolizumab was associated with encouraging response rates and safety data in patients with melanoma who may not respond to anti-PD-1 therapy, according to a press release.
“The findings were presented at the 9th World Congress of Melanoma — A Joint Meeting with the Society for Melanoma Research. The data include a phase 2 Immunopulse IL-12 (OncoSec) monotherapy study with 51 patients and a phase 2 study of the immunotherapy in combination with pembrolizumab, which included 22 patients.”
“Adding the immune stimulator ImmunoPulse IL-12 to pembrolizumab (Keytruda) produced promising activity among patients with melanoma identified as unlikely responders to anti–PD-1 therapies.
“Data from the phase II OMS-I102 trial presented at the 2017 World Congress of Melanoma showed that the combination induced an overall response rate (ORR) of 50% (n = 11) among 22 patients with baseline biomarker data suggesting they would not respond to anti–PD-1 therapy.”
“The FDA granted fast track designation to ImmunoPulse IL-12 for the treatment of metastatic melanoma that progressed during therapy with pembrolizumab or nivolumab.
“ImmunoPulse IL-12 (OncoSec Medical) is an intratumoral anticancer gene therapy that expresses interleukin-12 (IL-12).
“ ‘With the number of melanoma patients now being treated with either pembrolizumab (Keytruda, Merck) or nivolumab (Opdivo, Bristol Myers Squibb) in either the first- or second-line settings, there will be an increasing number of patients who will not respond to therapy,’ Punit Dhillon, president and CEO of OncoSec, said in a company-issued press release. ‘Thus, there is a clear need for treatments that can rescue these patients and help them benefit from these immunotherapies.’ ”
“Intratumoral plasmid interleukin-12 electroporation was associated with local necrosis and increased tumor infiltrating lymphocytes and can lead to systemic tumor regression in melanoma, according to study results presented at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.
“These benefits warrant the study of plasmid interleukin (IL)-12 electroporation in combination with anti-programmed cell death-1 (PD-1) monoclonal antibodies, Alain Algazi, MD, of the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, said during his presentation.
“ ‘IL-12 is a key cytokine, and might be really important in terms of stimulating an anti-tumor immune response, but if you give it systemically, it is toxic,’ Algazi said. ‘This is a way that you can give a concentrated amount of IL-12 into the tumor, with a focal intervention that is more tolerable.’
“Algazi and colleagues developed a platform for treatment where researchers inject plasma DNA into the tumor and then give an electric current to the site in order to make holes in the tumor cells. The tumor can then take up the plasma and start expressing IL-12.”
The gist: A new treatment called ImmunoPulse has shown promise for improving the long-term survival of metastatic melanoma patients. ImmunoPulse delivers instructions for making a protein called IL-12 into a patient’s tumor; the patient’s cells then make IL-12, which boosts the immune system to kill cancer cells. It was tested in 24 volunteer patients in a clinical trial in 2007. Now, long-term follow-up data has been analyzed. The researchers found that the median length of time patients lived after treatment was 23.9 months.
“OncoSec Medical Inc. (OTCQB: ONCS), a company developing DNA-based cancer immunotherapies, released long-term survival results from its Phase I study in patients with metastatic melanoma, evaluating a single treatment cycle of intratumoral plasmid IL-12 (pIL-12) injection with electroporation (EP). Dr. Robert Pierce, Chief Scientific Officer at OncoSec, a co-author of the abstract presented these data today at the Melanoma Bridge 2014 conference in Naples, Italy.
“The Phase 1 dose-escalation study, which completed enrollment in February 2007 and was first published in the Journal of Clinical Oncology (Daud et al., 2008), established that a single treatment cycle of intratumoral pIL-12 EP, administered on Days 1, 5 and 8, has an acceptable safety profile and is well-tolerated. Escalating concentrations of pIL-12 were administered in cohorts of three patients. No dose-limiting toxicities, treatment-related serious adverse events, or treatment-related Grade 4 or 5 adverse events were reported. Importantly, the study also demonstrated that local intratumoral pIL-12 EP can induce systemic responses, as evidenced by stable disease or objective regression in non-injected, non-electroporated lesions. Moreover, pIL-12 EP monotherapy was shown to achieve objective responses in this initial Phase 1 trial in patients with metastatic melanoma, with three complete responses (CRs) observed after only one treatment cycle.
“OncoSec collected data from long-term follow-up and determined that the median overall survival for the patients in the Phase 1 study was 23.9 months. In addition, a statistically significant difference (p = 0.0054) was observed when comparing overall survival between patients who had a best overall response of at least stable disease or better (median OS = 49.1 months) versus patients who only had disease progression while on study (median OS = 10.9 months).”
Every year, new cancer treatment insights are shared at the American Society of Clinical Oncology (ASCO) Annual Meeting. Here are some of the most notable recent developments in melanoma treatment, gleaned from researchers’ presentations at ASCO last month: Continue reading…
“OncoSec Medical Inc. (OTCQB: ONCS), a company developing its ImmunoPulse DNA-based intratumoral cancer immunotherapy, announced interim data from its Phase 2 melanoma study at the American Society of Clinical Oncology’s (ASCO) 50th Annual Meeting in Chicago. The abstract, titled “Systemic anti-tumor effect and clinical response in a Phase 2 trial of intratumoral electroporation of plasmid interleukin-12 in patients with advanced melanoma” (ASCO Abstract #9025), was presented by Adil Daud, M.D., OncoSec’s Chief Clinical Strategist and Principal Investigator of the Phase 2 melanoma study, and selected for discussion during a poster highlights session for melanoma/skin cancers led by Axel Hauschild, M.D., Ph.D.”
Editor’s note: This article describes a promising immunotherapy treatment that boosts a patient’s own immune system to fight melanoma.
An experimental immunotherapy that delivers interleukin-12 (IL-12) directly into a melanoma tumor may also shrink tumors elsewhere in the body. Called ImmunoPulse, the treatment entails injecting a tumor with interleukin-12 DNA and delivering electric shocks to make the tumor cells absorb this DNA. These cells then produce IL-12, boosting the immune response against the tumor. In an ongoing phase II trial of 21 people with melanomas that were treated with ImmunoPulse, tumors shrank in 8 of them (38%) and disappeared for at least 6 months in 2 more of them. Moreover, untreated tumors also shrank in about 60%. The possibility of body-wide effects is encouraging because, in contrast to systemic IL-12 therapy, ImmunoPulse treatments have yet to cause serious side effects.