Early survival data boost Ziopharm's 'controlled IL-12' immunotherapy for glioblastoma
An unconventional pairing of a gene therapy and an oral drug that promises to attack recurrent or progressive glioblastoma with controlled release of IL-12 has turned up more promising — if early — overall survival data. On top of boosting its case as a monotherapy, the data can also bode well for a combination with Regeneron’s PD-1 inhibitor, Libtayo.
Both the treatment and its developer, Ziopharm Oncology, have come a long way. The stock price peaked in 2015 but cratered in 2016 following a patient death in a Phase I.
Long-term follow-up data from the study, though, suggest that Ad-RTS-hIL-12 plus veledimex (Ad+V) is not only safe but helps patients live beyond a year. Across the main and expansion studies, the subgroup of patients receiving the low-dose corticosteroids — totaling 20 — showed median overall survival of 16.2 months.
“We know from conversations with regulators that median overall survival (mOS) is used as a benchmark to help determine the potential approval of new treatments for recurrent (rGBM),” CEO Laurence Cooper told Endpoints News. “Therefore, this survival endpoint is what we are using to gauge success of our Controlled IL-12 candidate.”
Historically, unifocal recurrent glioblastoma multiforme patients only live for 6 to 12 months, he added, meaning there’s a 30% “addition” of life for patients.
By injecting a vector that carries the gene for IL-12 — a powerful interleukin that’s referred to as a “master cytokine” for its ability to orchestrate an immune response — Ziopharm’s goal is to stir up T cell response against hard-to-treat cancer. But to ensure that the immune system doesn’t get out of control, the biotech has invented an oral activator ligand such that physicians can tune how much IL-12 to release, by remotely instructing the patients to adjust the dose.
Corticosteroids provide an extra level of protection, although it could also dampen the immune activity — which Cooper said explains why the patients on the lowest dose of steroids seem to have the best response to their therapy.
Investigators have previously noted increased checkpoint signaling, an observation that led them to test a combination of Ad+V and nivolumab (Opdivo). At 8.3 months of median follow-up, mOS has not been reached. Regeneron has signed on to test the combo approach with its own PD-1 drug, and the Phase II study is ongoing.
The latest update across three trials also brought the tally of partial responses to five.
“Observing responses in brain tumors in the setting of recurrence is unusual and highly encouraging, and, along with the survival data, highlight the potential of Ad+V for the treatment of rGBM,” said Antonio Chiocca, a trial investigator based at Dana-Farber and Brigham and Women’s Hospital.