Ziopharm Oncology Initiates Phase 2 Trial Evaluating Combination Therapy of Controlled IL-12 with Libtayo® (cemiplimab-rwlc) to Treat Patients with Recurrent Glioblastoma
“We piloted the combination of interleukin-12 (IL-12) and a PD-1-specific antibody in a phase 1 trial which lays the foundation for recruitment to this phase 2 study for patients with rGBM. This trial seeks to further IL-12, which activates the patient’s own immune system to attack cancer, by coupling with the inhibition of PD-1 to enhance the effectiveness of the combination,” said
Ziopharm’s Controlled IL-12 platform is an investigational gene therapy designed to induce and control the production of human interleukin 12 (hIL-12) a master-regulator of the immune system. In the setting of rGBM, the Company is leveraging the anti-tumor effects for Controlled IL-12 as monotherapy by combining with PD-1 inhibitors. Previously reported data from serial biopsies in patients with rGBM revealed that Controlled IL-12 results in sustained influx of T cells and upregulation of PD-1 expression, providing a compelling rationale for this combination. Initial phase 1 data from this trial were presented at the
The open-label, single-arm phase 2 trial will enroll approximately 30 patients with rGBM, with the primary endpoints being safety and efficacy. Patients with rGBM scheduled for resection who have not been treated previously with inhibitors of immune-checkpoint pathways will receive Ad-RTS-hIL-12 intratumorally at the time of surgical resection plus a dose of veledimex (20mg), an oral activator ligand, daily for 14 days. Patients will receive cemiplimab intravenously (350 mg) every three weeks until documented progression or withdrawal from the study.
Regeneron, in collaboration with
Additional information about the study will be available at https://clinicaltrials.gov.
About Ad-RTS-hIL-12 plus veledimex
The Company has treated more than 100 patients, including more than 75 patients with rGBM, with Ad-RTS-hIL-12 plus veledimex and administered more than 1,300 doses of veledimex across three types of solid tumors, building a significant safety profile, mechanistic dataset and evidence of anti-tumor effects.
At the 2018 annual meeting of the
In February, the Company announced that it rapidly completed enrollment and treated 36 additional patients at 20mg veledimex dosing in less than six months in a substudy (Clinicaltrials.gov NCT03679754) to expand a phase 1 trial evaluating its Controlled IL-12 platform as a monotherapy for the treatment of rGBM. A majority (75%) of patients enrolled in the substudy were treated with low-dose steroids. At
About Ad-RTS-hIL-12 plus veledimex in combination with PD-1 inhibitors
In a separate phase 1 trial to evaluate Controlled IL-12 in combination with the PD-1 inhibitor nivolumab, (Clinicaltrials.gov NCT03636477), the Company reported initial data and observations at the 2019 ASCO Annual Meeting earlier this month. With a mean follow-up of 4.5 months, the Cytoindex (an emerging biomarker) improved compared with Ad+V as monotherapy lending support that the combination may lead to improved overall survival. Data from three dosing cohorts evaluated increasing doses of veledimex and PD-1 inhibitor revealed a similar safety profile as Ad+V monotherapy. Adverse reactions from all cohorts were manageable and reversible without synergistic toxicities, while adverse reactions during follow-on nivolumab dosing were consistent with reports for PD-1 inhibition. Seven of the 9 patients in the study received low-dose steroids. The Company has completed dose escalation and anticipates enrolling additional patients with rGBM (to receive 20 mg of veledimex and 3 mg/kg of nivolumab).
FDA Fast Track Designation
Learn more about Controlled IL-12 online at https://ziopharm.com/controlled-il-12/.
Note Regarding Forward-Looking Statements
This news release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as "may," "will," "could," "expects," "plans," "anticipates," and "believes." These statements include, but are not limited to, statements regarding the potential clinical benefits of its Controlled IL-12 program in treating patients with rGBM and the progress and timing of the development of Ziopharm’s research and development programs, including the timing for the initiation and completion of its clinical trials. Although Ziopharm’s management team believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Ziopharm, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, changes in our operating plans that may impact our cash expenditures, the uncertainties inherent in research and development, future clinical data and analysis, including whether any of Ziopharm’s product candidates will advance further in the preclinical research or clinical trial process, including receiving clearance from the
VP, Investor Relations and Corporate Communications
Source: ZIOPHARM Oncology Inc