The Department of Neurosurgery at Brigham and Women’s Hospital (BWH) is involved in cutting-edge clinical trials using immunotherapies to treat glioblastoma.

Upcoming Clinical Trial Using Combination Therapy for Newly Diagnosed Glioblastoma Patients

In the spring of 2018, investigators from the Department of Neurosurgery at Brigham and Women’s Hospital (BWH) will begin enrolling patients for a multi-institutional clinical trial for newly-diagnosed glioblastoma patients. The trial will run at multiple institutions with BWH being the lead site.

The trial will involve a combination therapy to treat brain tumors. At the time of surgery, patients will receive a gene therapy vector Adenoviral vector-TK (Ad-TK, GMCI) and valacyclovir, followed by standard chemoradiation and an immune checkpoint inhibitor.

“In previous clinical trials, using only a gene therapy vector, we showed an increase in median survival to 25 months from historical controls of 15 months. We hope to achieve even better survival outcomes when adding a checkpoint inhibitor,” says E. Antonio Chiocca, MD, PhD, chair of the Department of Neurosurgery at BWH. As principal investigator, Dr. Chiocca is collaborating with Patrick Y. Wen, MD, director of the Center for Neuro-Oncology at Dana-Farber/Brigham and Women’s Cancer. The trial will be conducted with the American Brain Tumor Consortium (ABTC) and is sponsored by Advantagene, Inc.

Investigators within the Department of Neurosurgery at BWH recently completed a Phase 1 dose escalation trial that included adult patients with recurrent or progressive Grade III or IV glioma undergoing resection.

The trial involved the injection of a novel gene therapy, Ad-RTS-hIL-12, which expresses IL-12 under the control of an oral activator ligand, veledimex, via the RheoSwitch Therapeutic System® gene switch. The median overall survival (mOS) of all patients receiving intratumoral Ad-RTS-hIL-12 with 20 mg of orally-administered veledimex was maintained at 12.5 months, with a mean follow-up time of 9.2 months. The trial was sponsored by Ziopharm, Inc.

“With Ad-RTS-hIL-12 + veledimex, we can control IL-12 expression within the tumors. This offers the potential to safely direct one of the most potent anti-cancer immune cytokines against glioblastoma,” says Dr. Chiocca.

Dr. Chiocca presented data at the 2017 American Society of Neuro-Oncology Annual Meeting in San Francisco, and is in the process of preparing these data for publication.

Phase 1 Trial of Herpes Simplex Virus in Recurrent Glioblastoma Patients

Dr. Chiocca is the principal investigator for a phase 1 trial that is currently enrolling patients with recurrent or progressive glioblastoma. In this trial, brain tumors will receive an injection of a novel oncolytic herpes simplex virus type 1 (oHSV1).

This novel oHSV was shown to infect human cells with high-efficiency and showed a rapid lytic cycle (12-18 hours). In preclinical studies, animal survival was 80 percent when OV was injected seven days after tumor implant; animal survival was 50 percent when OV was injected 14 days after tumor implant.

“It’s taken 15 years to get from inventing this virus in my own laboratory to a clinical trial with humans. This trial will be the first time a glioblastoma stem-like specific oncolytic HSV1 has been injected in man,” says Dr. Chiocca. “The injected oncolytic HSV1 potentially targets all cells, but particularly targets Nestin-expressing cells. Nestin is a marker of glioblastoma ‘Stemness.’”

“Glioblastoma is one of the most aggressive and lethal cancers, and new therapies are urgently needed. These trials are cutting edge, and a significant number of patients will ultimately benefit from them,” says Dr. Chiocca.

Video Highlight: Significant Updates in Glioblastoma from ASCO 2017

Dr. Wen sat with down with Practice Update to discuss glioblastoma research and findings from BWH.