Ziopharm Oncology Announces Publication of Positive Results of Phase 1 Monotherapy Trial of Controlled IL-12 in Patients with Recurrent Glioblastoma in Science Translational Medicine
– Ad-RTS-hIL-12 plus 20 mg veledimex (Controlled IL-12 platform) determined to be the preferred dose
with low-dose steroids to treat adult patients with recurrent glioblastoma –
– Median overall survival for Controlled IL-12 in patients receiving low-dose steroids was 17.8 months –
– Increased tumor infiltrating lymphocytes and PD-1 (programmed cell death protein 1) support
immunological anti-tumor effect of Controlled IL-12 –
While IL-12 is known as a potent immune activator that triggers T cells to target cancer, historic trials systemically infusing IL-12 protein have failed due to intolerable toxicity. In contrast, this study showed that a ligand-inducible gene switch regulates expression of IL-12 from the central nervous system, resulting in increased cytokine and T-cell activity within the tumor environment, while preserving a favorable safety profile.
Glioblastoma is an aggressive, largely incurable cancer. Patients receive surgery, radiation and chemotherapy, but in almost all cases, tumors return within months. When this brain cancer recurs, median overall survival is six to nine months.1,2
The paper includes data from 31 patients with recurrent glioblastoma (rGBM) treated with Controlled IL-12 (Ad-RTS-hIL-12 plus veledimex, Ad+V). Frequency and severity of adverse events, including cytokine release syndrome, correlated with the veledimex (ligand) dose, reversing promptly upon discontinuation. The 20 mg veledimex dose had superior drug compliance and demonstrated 12.7 months median overall survival (mOS) at a mean follow-up of 13.1 months. Concurrent corticosteroids negatively impacted survival and patients had further improved mOS of 17.8 months when cumulative amount of dexamethasone was limited to less than 20mg during active veledimex dosing.
“I would like to thank the site teams and investigators, as well as all of the patients who participated in this trial,” said
“In a phase 1 trial, we strive to show that a new drug candidate is first and foremost safe for patients and at the same time, aim to demonstrate initial evidence of efficacy,” said corresponding author
“Glioblastoma at recurrence is a devastating cancer with few treatment options that have demonstrated success. These updated data show a promising extension of patients’ survival and demonstrate how controlling the powerful cytokine IL-12 can engage the body’s own immune system to generate an anti-tumor response against rGBM,” said co-author Rimas V. Lukas, M.D., Associate Professor of Neurology (Neuro-Oncology),
About Controlled IL-12 (Ad-RTS-hIL-12 plus veledimex)
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. 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.
The Company announced earlier this year the completion of the enrollment in an “Expansion Substudy” (Clinicaltrials.gov NCT03679754) that enlarged the phase 1 trial by an additional 36 patients with Ad-RTS-hIL-12 plus 20mg/day veledimex for up to 14 days. In that cohort, 75% of patients (27/36) received low-dose steroids.
About Controlled IL-12 in combination with PD-1 inhibitors
Ziopharm is also advancing Ad-RTS-hIL-12 plus veledimex for the treatment of rGBM in combination with immune checkpoint inhibitors. In
The Company announced in
Fast Track and Orphan Medicinal Product Designations
Learn more about Controlled IL-12 online at https://ziopharm.com/controlled-il-12.
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Source: ZIOPHARM Oncology Inc