The first patient has been dosed in a Phase 2 trial assessing the safety and preliminary efficacy of PVSRIPO in combination with Keytruda (pembrolizumab) as a treatment for people with recurrent glioblastoma multiforme (rGBM), an aggressive form of brain cancer.
The open-label study, called LUMINOS-101 (NCT04479241), aims to enroll around 30 adults with rGBM from several clinical sites across the U.S. More information about trial contacts and recruiting sites can be found here.
The 24-month study is sponsored by PVSRIPO’s developer, Istari Oncology.
“The initiation of this Phase 2 trial represents a significant milestone in the advancement of PVSRIPO and our quest to treat this formidable opponent,” Matt Stober, Istari’s president and CEO, said in a press release.
“Currently the treatment options for patients with rGBM are limited and outcomes are grim, so following the encouraging results of our Phase 1 trial, we are eager to see the effectiveness of PVSRIPO in combination with pembrolizumab,” Stober said.
PVSRIPO is a new form of immunotherapy that uses a virus based on the attenuated, or less virulent form, of the Sabin type 1 polio vaccine. The virus making up PVSRIPO has been genetically engineered to ensure it cannot infect and harm healthy cells. Instead, it is designed to specifically target tumor cells and certain types of immune cells containing the poliovirus receptor CD155.
While infected cancer cells are increasingly damaged and eventually destroyed by the virus, infected immune cells become more active and primed to attack malignant cancer cells. Thus, PVSRIPO is expected to elicit strong anti-cancer responses by destroying tumor cells directly, and at the same time, triggering strong immune and inflammatory responses against tumors.
LUMINOS-101 will investigate a combination of PVSRIPO plus Keytruda, an immune checkpoint inhibitor developed by Merck (or MSD outside of the U.S. and Canada). Keytruda has been approved by the U.S. Food and Drug Administration to treat a range of advanced cancers.
Here, the combination treatment is designed to prevent cancer cells from evading the body’s immune system in rGBM patients who failed one to two prior lines of therapy.
“Combining PVSRIPO’s ability to generate antitumor immune response with a checkpoint inhibitor holds the promise of more effective therapy for this devastating disease,” said W. Garrett Nichols, MD, chief medical officer at Istari Oncology.
During the trial, participants will first receive an injection of PVSRIPO directly into the tumor, followed by intravenous (into-the-vein) Keytruda, every three weeks, starting two to four weeks after the initial treatment.
The study’s main goals are to determine the percentage of patients responding to the therapy, as well as its safety and tolerability. Additional measures include the effects of treatment on patients’ survival and disease progression.
LUMINOS-101 builds upon an earlier Phase 1 trial (NCT01491893) that demonstrated that rGBM patients who received PVSRIPO had higher survival rates compared with those treated with standard therapies in other studies.
Interim data from this Phase 1 study showed that overall survival rates reached a plateau of 21% two years after PVSRIPO treatment, which was maintained at three years following treatment.
“The Phase 1 trial of PVSRIPO yielded survival rates like we’ve never seen before,” said Andrew E. Sloan, MD, director of the Brain Tumor & Neuro-Oncology Center at the University Hospitals Seidman Cancer Center (UHSCC) in Cleveland, Ohio.
UHSCC is one of the study sites, and is where the first patient was dosed.
“Glioblastoma is one of the most aggressive tumors known to man,” added Sloan, also a professor and vice chairman at Case Western Reserve University School of Medicine.
“Following the encouraging results of PVSRIPO to date, we are very interested to see if those results improve further in combination with pembrolizumab,” he said.
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