November 14, 2020 – Treatment with the novel intratumoral immuotherapy agent PVSRIPO resulted in an overall response rate of 33% among all patients with anti–PD-1 refractory melanoma.
Treatment with the novel intratumoral immuotherapy agent PVSRIPO resulted in an overall response rate (ORR) of 33% among all patients with anti–PD-1 refractory melanoma. Further, data from a phase 1 study demonstrated a 67% response among those who underwent a full course of treatment. However, investigators said it is too early to draw definitive conclusions based on these results because of the small trial population of 12 patients.
Four (33%) patients in the study met criteria for a total ORR. That number included 4 of the 6 (66%) patients who received a maximum course of treatment, 3 injections over 21 days. Investigators said this result suggests that intratumoral PVSRIPO could initiate or rekindle responses in patients who have failed anti-PD-1 therapy.1
Two of 4 (50%) patients with in-transit disease had pathologic complete response. At a median follow-up of 12 months, 50% (6/12) patients remained progression free.
Most patients received additional immune checkpoint inhibitor (ICI)-based therapy after study completion (83%). Investigators noted a response following subsequent ICI therapy, which suggests that combination therapy may induce stronger response.1
“The majority of patients with melanoma have primary resistance to anti–PD-1 therapy and up to 40% of those with initial response may acquire resistance over the course of treatment,” said lead author Georgia Beasley, MD, during a presentation at the 2020 SITC Annual Meeting. “PVSRIPO is a unique investigational intratumoral immunotherapy being studied to assess its ability to fight cancers either alone or in combination with immune checkpoint inhibitors.” Beasley is an assistant professor of surgery and assistant program director for the complex general surgical oncology fellowship at Duke University of Medicine.
PVSRIPO is a novel immunotherapy based on the Sabin Type-1 polio vaccine that is injected directly into tumors. The recombinant oncolytic poliovirus is designed to infect antigen-presenting cells, such as macrophages and dendritic cells that express CD155. The poliovirus receptor is often expressed on malignant cells of solid neoplasia, as well as in myeloid and endothelial cells. Following tumor infection, a series of acute inflammatory events allows for immune cell invasion and the creation of an immunogenic microenvironment.2
Investigators recruited 12 patients with unresectable and/or metastatic melanoma who failed at least 1 anti–PD-1-based regimen and patients with BRAF V600 mutations also failed at least 1 BRAF-targeted therapy to the phase 1 open-label trial (NCT03712358). Patients were assigned to 1 of 3 treatment groups. Cohort 1 received PVSRIPO injected into 1 lesion on day 1 and a second lesion on day 21. Cohort 2 received PVSRIPO into 3 separate lesions 21 days apart, and cohort 3 received 3 injections into 1 lesion 21 days apart.1
The primary objective was to evaluate the safety, tolerability, efficacy, and immune activation of PVSRIPO in patients with advanced melanoma. Beasley said investigators recorded responses in both tumors that were injected with PVSRIPO and uninjected tumors.
All adverse events (AEs) were mild (grade 1/2). Investigators observed no serious adverse events or dose-limiting toxicities. Grade 1 pruritis (50.0%) and erythema (33.3%) were the most common treatment-related AEs.
Investigators observed no evidence of viral spread from the intratumoral inoculation site. They hypothesized that preexisting antipoliovirus immunity and CD155 targeting likely restricted viral spread and off-target/systemic immune related AEs.1
Based on these results, Istari Oncology, the manufacturer of the agent, is proceeding with the multicenter, open-label, randomized phase 2 LUMINOS-102 trial (NCT04577807). Following a 6-participant safety run-in, investigators will assess the efficacy and safety of PVSRIPO alone or in combination with an anti-PD-1 inhibitor in patients with cutaneous or mucosal melanoma who previously failed anti-PD-1 blockade.
In 2016, PVSRIPO was granted a breakthrough therapy designation by the FDA for the treatment of patients with recurrent glioblastoma. In updated findings, published in the New England Journal of Medicine, the agent demonstrated a 2- and 3-year overall survival (OS) rate of 21% (95% CI, 11%-33%).3
At 27.6 months follow-up the median OS was 12.5 months with PVSRIPO (95% CI, 9.9-15.2) compared with 11.3 months in a historical control group (95% CI, 9.8-12.5). The OS rate continued to decline beyond 1 year in the historical control group but plateaued at 21% for PVSRIPO.3