Biodistribution, shedding, and transmissibility of vusolimogene oderparepvec (RP1).

BACKGROUND

Vusolimogene oderparepvec (RP1) is an intratumorally administered, genetically modified herpes simplex virus type-1 derived oncolytic immunotherapy designed to selectively replicate in tumors and stimulate systemic antitumor immunity. We evaluated the biodistribution, shedding, and potential for transmission of RP1 in patients with skin cancers treated in the IGNYTE clinical trial and assessed close-contact exposure across all RP1 clinical studies.

METHODS

Patients received intratumoral RP1 in combination with nivolumab, with serial collection of blood, urine, injection-site, dressing, and oral mucosal samples during treatment and follow-up. RP1 DNA was quantified by polymerase chain reaction, and swab samples positive for RP1 DNA were tested for replication-competent RP1. Reports of herpetic infection in patients and close contacts were also systematically collected.

RESULTS

Among 282 treated patients, RP1 DNA was detected most frequently at injection sites, with substantially lower incidence and levels in other sample types. Detection declined rapidly after treatment completion, with no RP1 DNA detected in blood or urine during follow-up. Replication-competent RP1 was detected rarely and only at low titers, only at injection sites. No systemic herpes simplex virus infections occurred in patients, and no herpetic infections were reported among caregivers or close contacts.

INTERPRETATION: RP1 is largely confined to injection sites, shedding of live RP1 is rare and transient. No evidence of transmission of RP1 was observed. These findings support the favorable biosafety profile of RP1 with only a negligible risk of environmental release or secondary transmission during clinical use.