Biosafety analysis from the skin cancer cohorts in the IGNYTE clinical trial of RP1.

RP1 (vusolimogene oderparepvec) is an HSV–based oncolytic immunotherapy administered intratumorally. RP1 + nivolumab (nivo) has demonstrated deep, durable responses with favorable safety in advanced melanoma. We report biodistribution and shedding data from the skin cancer cohorts of the IGNYTE trial (NCT03767348) Following RP1 injection into superficial and/or deep lesions, injection sites were covered with occlusive dressings. Injection sites, dressings and mucosa were swabbed, and blood and urine were collected pre-dose, during treatment, and at follow-up visits. Samples were assessed for RP1 DNA by qPCR. Swab samples positive for RP1 DNA were further assessed by TCID50 assay for live RP1. The highest incidence of RP1 DNA was from injection-sites where RP1 was detected in ~35% of samples for up to 15 days post-injection. Blood samples showed the presence of low copy numbers of RP1 DNA (122/1573 [7.8%]) in ~20% (53/274) of pts during or after RP1 treatment. The highest levels were detected in blood within 6 hours of injection and decreased thereafter. RP1 was only very rarely detected and at low copy number in urine samples (3/1976 [0.2%]) from 0.7% (2/273) pts at 15 days post-injection, with all subsequent samples testing negative. RP1 DNA was detected on injection-site dressing exteriors less often (9.5% of 1114 samples) than from injection sites (18.4% of 1947 samples), demonstrating that the dressings act as a barrier to RP1. RP1 DNA was rarely present on oral mucosa (0.9% of 2052 samples). At follow-up (30-100 days post last dose), RP1 DNA was detected only at injection-sites. All available samples were negative for live RP1 by TCID50. Eight swab samples from 7 pts were collected from suspected herpetic infections but all tested negative for live RP1. There were no reports of systemic herpetic infections in pts, nor of transmission to contacts. RP1 DNA was primarily detected on the surface of injected lesions for up to 15 days, with no live RP1 being detected at 30, 60 and 100 days post the last RP1 dose. Collectively, these data demonstrate that RP1 is rapidly cleared from blood and urine, with negligible likelihood of environmental dissemination or transfer to contacts, and that the use of occlusive dressings contains RP1.Defining the biodistribution and shedding of RP1 is relevant to the education of healthcare providers and to the development of best practices for the proper administration, handling and clean down. .

Duke Scholars

Author Georgia Marie Beasley Surgical Oncology