On June 28, 2017 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new immunotherapies, reported the initiation of enrollment in the stereotactic arm of its Phase 1 multicenter study of Ad-RTS-hIL-12 + veledimex, a gene therapy for controlled expression of IL-12, in patients with recurrent glioblastoma multiforme (rGBM) (Press release, Ziopharm, JUN 28, 2017, View Source [SID1234519708]). The stereotactic cohort will include rGBM patients that are not scheduled to undergo surgical resection to assess the safety and tolerability of a single dose of Ad-RTS-hIL-12 administered via injection and activated with orally-administered veledimex (20 mg QD, days 1-14). Schedule your 30 min Free 1stOncology Demo! "Supported by strong clinical data highlighting the potential for controlled immune activation to affect survival outcomes in recurrent GBM, we are expanding our innovative Ad-RTS-hIL-12 + veledimex gene therapy into new treatment settings and combinations," said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM. "By introducing stereotactic administration, we broaden the population of patients who may be eligible for treatment, including pediatric patients with diffuse intrinsic pontine glioma, a rapidly fatal and inoperable form of brain cancer. Additionally, preclinical studies of this tunable IL-12 gene therapy in combination with an immune checkpoint inhibitor have yielded promising results, notably a 100 percent survival rate of treated mice, and we look forward to bringing this approach into the clinic."
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Following an observation period, the Company expects to immediately:
Initiate enrollment in a study of adult patients with rGBM who will receive a single dose of Ad-RTS-hIL-12 + veledimex in combination with a checkpoint inhibitor targeting programmed cell death protein 1 (PD-1);
Initiate enrollment in a study of pediatric patients with recurrent/progressive glioma who will receive a single dose of Ad-RTS-hIL-12 + veledimex. The Company anticipates children with diffuse intrinsic pontine glioma (DIPG) will be eligible for enrollment.
At the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held in June, the Company reported encouraging results from patients receiving intratumoral Ad-RTS-hIL-12 with 20 mg of orally-administered veledimex (n = 15) following craniotomy, with a median overall survival (mOS) of 12.5 months comparing favorably to historical controls. Based on the observed ratio of CD8+/FOXP3+ (effector/suppressor) T cells, overall survival appears directly correlated with IL-12-mediated cellular immune activation. Furthermore, patients who received low dose steroids have a much better survival rate than those who received elevated systemic steroids, as the latter presumably interferes with immune activation. The Company continues to progress towards a registration study for Ad-RTS-hIL-12 + veledimex for rGBM to start in 2017 and is also evaluating partnership opportunities for this promising treatment candidate.
"Stereotactic treatment serves as a runway into our next phase of development for Ad-RTS-hIL-12 + veledimex including combination therapy and pediatric studies," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM Oncology. "We anticipate translating the combination approach to patients imminently and further leveraging initial observations on the survival benefit of IL-12-driven immune activation. As a pediatric oncologist, I know full well the devastating impact of DIPG and am also looking forward to seeing the effect of controlling IL-12 in this difficult-to-treat disease."
Brain tumors
Recurrent GBM represents approximately 15% of all primary adult brain tumors and remains a high unmet clinical need that affects roughly 74,000 people worldwide annually.i,ii GBM is an aggressive form of brain cancer with recurrence rates near 90%, and prognosis for patients is poor with treatment often combining multiple approaches including surgery, radiation, and chemotherapy. Patients with recurrent GBM typically have a mOS of 6-7 months, and overall survival in patients who have failed temozolomide, bevacizumab or equivalent salvage chemotherapy, is approximately 3-5 months.iii,iv DIPG is a rapidly progressive brain tumor of children with tragically near universal fatal outcomes and a median survival less than 12 months.v