Istari Oncology, a young Research Triangle Park biotechnology company started by a world-famous Duke University brain cancer team, has reported rare positive results in a Phase 1 clinical trial of its experimental treatment for glioblastoma.
The clinical-stage company, which is developing novel immuno-oncology and immunotherapy platforms to treat not only glioblastoma, but a wide variety of tumors, announced results of its Phase 1 trial of its treatment based on an inactivated polio virus, PVSRIPO, in recurrent glioblastoma.
The study, published in The New England Journal of Medicine (NEJM), was conducted by The Preston Robert Tisch Brain Tumor Center at Duke. PVSRIPO, an acronym for Polio Virus Sabin-Rhinovirus Poliovirus, has been granted Breakthrough Status and Orphan Status by the U.S. Food and Drug Administration.
Four years ago the North Carolina Biotechnology Center awarded a $50,000 Technology Enhancement Grant to the Duke University Medical Center that allowed Duke to acquire and contract the manufacture of the PVSRIPO therapy from the National Cancer Institute at Ft. Dedrick, Md.
In this trial of 61 adult patients, overall survival at 24 and 36 months was 21 percent, compared to 14 percent at 24 months, and 4 percent at 36 months in matched historical controls. Three patients receiving PVSRIPO have survived beyond 60 months.
“The impressive results with PVSRIPO in this trial are the best we have seen to date in patients with recurrent glioblastoma and provide hope for these patients whose typical survival time is less than a year,” said Henry S. Friedman, M.D., chief medical officer of Istari and James B. Powell, Jr. professor of neuro-oncology and the division chief for neuro-oncology in Tisch Brain Tumor Center in the Department of Neurosurgery at Duke.
“Based on the observation that the receptor for PVSRIPO, CD155, is present on almost all solid tumors, we look forward to future trials in other cancers, as well as glioblastoma, both alone and in combination with other agents, as we strive to provide hope for these patients as well.”
Study weighs toxicity, best dosage
The primary objective of the Phase 1 study was to determine the toxicity and the best phase 2 dose to use in subsequent clinical trials. The secondary objective was to estimate overall survival compared to an historical control group.
From May 2012 to May 2017, 61 consecutive adult patients with recurrent glioblastoma were enrolled in the study that evaluated seven doses. The median overall survival for all 61 PVSRIPO patients was 12.5 months compared to 11.3 months for the matched historical control group. However, the overall survival of PVSRIPO patients reached a plateau beginning at 24 months with 24- and 36-month overall survival of 21 percent, while the overall survival in the matched historical control continued to decline with 24-month overall survival of 14 percent, and 36-month overall survival of 4 percent. Of these survivors, two patients are beyond 70 months, and one patient is beyond 60 months.
Adverse events affecting more than 20 percent of patients in the dose-expansion phase included such things as headaches (52 percent), seizure (45 percent), dysphasia (communication problems) (28 percent), and cognitive disturbance (25 percent). The NEJM publication is available at https://www.nejm.org/.
A multi-center Phase 2 trial of PVSRIPO alone and in combination with chemotherapy in adults with recurrent glioblastoma is currently enrolling, with a primary endpoint of 24-month survival. A Phase 1 trial of PVSRIPO in pediatric patients with recurrent glioblastoma is also currently enrolling. More information on clinical trials with PVSRIPO is available on the Istari website.
The company has also generated positive preclinical data for PVSRIPO in multiple solid tumor models, both alone and in combination with other agents, including checkpoint inhibitors. Phase 1 trials are currently planned for PVSRIPO in breast cancer and melanoma.
Glioblastoma is the most common and aggressive form of brain cancer, comprising 52 percent of patients with primary brain tumors. There are approximately 13,000 patients diagnosed with it in the United States annually, and approximately 18,000 in the European Union.
Glioblastoma is the brain cancer killing Senator John McCain and that caused Senator Ted Kennedy’s death. It also led to the death of Steve Case’s brother.
Despite aggressive treatment, survival for newly diagnosed glioblastoma patients is usually less than 20 months, and for those with recurrence, which is 98 percent of patients, survival is usually less than 12 months.
About Istari Oncology
Privately held Istari was founded in 2016 by Darell Bigner, M.D., and Matthias Gromeier, M.D., of Duke University Medical Center. Both are leaders in their respective research fields of virology, immunology, monoclonal development and clinical medicine, particularly in treating brain tumors.
Istari licensed a broad range of patents and patent applications from Duke and has access to additional intellectual property created at Duke to continue clinical and commercial development of these technologies. The company’s two platforms currently in clinical development are PVSRIPO and Antibody-Directed Immuno-Conjugates (ADC).