Treatment with the recombinant poliovirus vaccine PVSRIPO in patients with recurrent glioblastoma can be delivered at a safe dose with efficacy that compares favorably with historical data, recently reported results of a phase 1, nonrandomized study suggest.

The survival rate at 36 months after intratumoral infusion of PVSRIPO was 21%, versus 4% in a control group of patients who would have met the study’s eligibility criteria, investigators wrote in the New England Journal of Medicine.

There was no evidence of virus shedding or viral neuropathogenicity in the study, which included 61 patients with recurrent World Health Organization grade IV malignant glioma. “Further investigations are warranted,” wrote Annick Desjardins, MD, of Duke University, Durham, N.C., and her coauthors.

The prognosis of WHO grade IV malignant glioma remains dismal despite aggressive therapy and decades of research focused on advanced surgery, radiation, chemotherapy, and targeted agents, Dr. Desjardins and her colleagues said.

Accordingly, they sought to evaluate the potential of PVSRIPO, a live-attenuated poliovirus type 1 vaccine with its viral internal ribosome entry site replaced by one of human rhinovirus type. The engineered virus gains entry via the CD155 receptor, which is upregulated in solid tumors such as glioblastomas and expressed in antigen-presenting cells.

“Tumor cytotoxic effects, interferon-dominant activation of antigen-presenting cells, and the profound inflammatory response to poliovirus may counter tumor-induced immunosuppression and instigate antitumor immunity,” the investigators wrote.

With a median follow-up of 27.6 months, the median overall survival for PVSRIPO-treated patients was 12.5 months, longer than the 11.3 months seen in the historical control group. It was also longer than the 6.6 months found in a second comparison group of patients who underwent therapy with tumor-treating fields, which involves application of alternating electrical current to the head.

Survival hit a “plateau” in the PVSRIPO-treated patients, investigators said, with an overall survival rate of 21% at both 24 and 36 months. That stood in contrast to a decline in the historical control group from 14% at 24 months to 4% at 36 months, and a decline from 8% to 3% in the tumor-treating-fields group.

The phase 1 study had a dose-escalation phase including 9 patients and a dose-expansion phase with 52 patients. In the dose-expansion phase, 19% of patients had grade 3 or greater adverse events attributable to PVSRIPO, according to the report.

Of all 61 patients, 69% had a vaccine-related grade 1 or 2 event as their most severe adverse event.

One patient death caused by complications from an intracranial hemorrhage was attributed to bevacizumab. As part of a study protocol amendment, bevacizumab at half the standard dose was allowed to control symptoms of locoregional inflammation, investigators said.

In an ongoing, phase 2, randomized trial, PVSRIPO is being evaluated alone or with lomustine in patients with recurrent WHO grade IV malignant glioma. The Food and Drug Administration granted breakthrough therapy designation to PVSRIPO in May 2016.

Seven study authors reported equity in Istari Oncology, a biotechnology company that is developing PVSRIPO. Authors also reported disclosures related to Genentech/Roche, Celgene, Celldex, and Eli Lilly, among other entities. The study was supported by grants from the Brain Tumor Research Charity, the Tisch family through the Jewish Communal Fund, the National Institutes of Health, and others.

SOURCE: Desjardins A et al .N Engl J Med. 2018 Jun 26. doi: 10.1056/NEJMoa1716435.

Recombinant poliovirus appears safe, active as recurrent glioblastoma treatment