David A. Reardon, MD, discusses the design of a phase 1/2 trial with INO-5401 and INO-9012 in glioblastoma.
David A. Reardon, MD, clinical director of the Center for Neuro-Oncology and an institute physician with Dana-Farber Cancer Institute, as well as a professor of medicine at Harvard Medical School, discusses the design of a phase 1/2 trial with INO-5401 and INO-9012 in glioblastoma.
The design of the trial was straightforward; it had 2 arms and it examined INO-5401 and INO-9012 in patients with newly diagnosed glioblastoma, says Reardon. A safety lead-in component of the study was conducted, as the vaccine complex of INO-5401 and INO-9012 had not been previously administered to patients with glioblastoma in the context of standard radiation therapy; it also had not been administered with PD-1 blockade, says Reardon. The safety lead-in confirmed that these agents were well tolerated and did not cause any significant, unexpected adverse effects.
In the phase 2 portion of the study, patients were divided into 2 arms. One group included those who had a O6-methylguanine DNA methyltransferase (MGMT) unmethylated promoter, which is seen in about two-thirds of patients with newly diagnosed glioblastoma; these patients are predicted to have a lower benefit rate from the standard-of-care therapy with temozolomide (Temodar), Reardon explained. The other arm of the study included patients with a MGMT promoter if their tumor was methylated, and these patients are predicted to have a higher likelihood of benefit from temozolomide.
All patients in the trial received radiation with daily temozolomide, as the agent has the potential to act as a radiosensitizer that may enhance the benefit of radiation therapy. This is what should be done in the context of an immunotherapy trial because immunogenic cell death and release of tumor antigens are needed to try and help enhance cross-priming against multiple tumor targets, concludes Reardon.