Ziopharm Oncology Inc., announced a clinical supply agreement with Regeneron Pharmaceuticals Inc. to evaluate Ziopharm’s Ad-RTS-hIL-12 plus veledimex in combination with Regeneron’s PD-1 antibody Libtayo (cemiplimab-rwlc) to treat patients with recurrent glioblastoma.
Ad-RTS-hIL-12 plus veledimex is an investigational gene therapy designed to induce and control the production of human interleukin 12 that activates the immune system and recruits cancer-fighting T cells into tumors.
Libtayo has been approved in the U.S. for the treatment of patients with metastatic cutaneous squamous cell carcinoma or locally advanced CSCC who are not candidates for curative surgery or curative radiation.
Under the agreement, Ziopharm and Regeneron will initiate a phase II study in the first half of 2019 in patients with rGBM to measure preliminary safety and efficacy of Ad-RTS-hIL-12 plus veledimex in combination with Libtayo.
Ziopharm will be responsible for the conduct and costs of the clinical trial, and Regeneron will supply Libtayo for the study. The companies potentially may explore the Ad-RTS-hIL-12 plus veledimex in combination with Libtayo in additional indications.
Regeneron, in collaboration with Sanofi, is developing Libtayo both alone and in combination with other therapies for the treatment of various cancers.
Ad-RTS-hIL-12 plus veledimex, within Ziopharm’s Controlled IL-12 platform, is a novel gene therapy candidate that conditionally expresses recombinant hIL-12 under the control of orally-administered veledimex.
This activator ligand acts via the proprietary RheoSwitch Therapeutic System gene switch to control transcription and thus expression of hIL-12. This cytokine is considered a master regulator of the immune system and has demonstrated an ability to activate and recruit killer T cells to sites of cancer resulting in anti-tumor responses.
A phase I study evaluating Ad-RTS-hIL-12 plus escalating amounts of veledimex administered to patients with rGBM revealed dose-dependent production of both hIL-12 as well as endogenous interferon gamma and biopsy data demonstrated an influx of CD3+CD8+ cytotoxic T cells and overexpression of PD-1/PD-L1 markers.
Data from this same trial showed a median overall survival of 12.7 months for patients treated with 20mg of veledimex (n=15) at a mean follow-up time of 12.9 months (as of May 4, 2018).
This compares favorably to the 5 to 8 months OS established in a similar patient population of historical controls with rGBM. Preclinical data from a mouse study evaluating Ad-RTS-mIL-12 plus veledimex to produce mouse IL-12 in combination with an anti-PD-1 are promising, including 100 percent survival in one dosing cohort.
