Vusolimogene oderparepvec

Vusolimogene oderparepvec is an oncolytic viral therapy which preferentially replicates within the tumor leading to tumor lysis, release of tumor and viral antigens, proinflammatory molecules, and infiltration of T cells. The GALV-GP-R^– expressed by vusolimogene oderparepvec increases direct tumor killing and the GM-CSF expressed by vusolimogene oderparepvec is intended to activate and mature dendritic cells and monocytes. In the anti-PD-1 resistant setting, vusolimogene oderparepvec and nivolumab in combination may promote an anti-tumor immune response.

No studies have been performed to evaluate the pharmacodynamics of vusolimogene oderparepvec.

Biodistribution and Viral Shedding

In the IGNYTE Study, vusolimogene oderparepvec biodistribution and viral shedding were assessed using a quantitative polymerase chain reaction (qPCR) assay. Blood, urine, and swab samples were collected from injection site(s), injection-site(s) dressings, and oral mucosa of 278 patients receiving vusolimogene oderparepvec. Samples were collected before dosing, during treatment, at 30 and 60 days following the last vusolimogene oderparepvec injection, and up to 100 days after the last dose of study treatment (either vusolimogene oderparepvec or nivolumab). Patients were asked to report any appearance of herpetic-like lesions in caregivers or close contacts. As the presence of DNA does not equate to live/infectious vusolimogene oderparepvec, DNA-positive swab samples were further assessed in a validated 50% tissue culture infectious dose (TCID50) assay, which detects live vusolimogene oderparepvec.

Vusolimogene oderparepvec DNA was detected in blood samples from 53 out of 274 (19%) patients within 6 hours of injection with decreasing levels thereafter. Vusolimogene oderparepvec DNA was detected in 3 out of 1976 (0.2%) urine samples. Vusolimogene oderparepvec is cleared from both blood and urine after 30 days, with all samples from follow-up visits testing negative for vusolimogene oderparepvec DNA. No sample had detectable vusolimogene oderparepvec DNA 30-days after the end of treatment in blood, urine, swab samples collected from injection site(s), injection-site(s) dressing, or oral mucosa. Vusolimogene oderparepvec DNA was detected on the surface of injected lesions in 112 of 266 (42%) patients, and 358 of 1947 (18%) tested samples. Consistent with the kinetics of vusolimogene oderparepvec replication in tumors, vusolimogene oderparepvec DNA was present at the injection site up to 15 days post injection in approximately 20% of patients. The incidence of detection of vusolimogene oderparepvec DNA in the exterior of injection site dressings was lower than at the injection site with samples from 43 of 207 (21%) patients' exterior of injection-site dressing samples testing positive for vusolimogene oderparepvec DNA. Positive samples were further assessed for live vusolimogene oderparepvec. Out of 314 samples, 4 tested positive by TCID50. The reported incidence of vusolimogene oderparepvec transmission to close contacts was 0%.

No differences in the incidence of detectable vusolimogene oderparepvec DNA were observed between patients who were HSV-1 seronegative or seropositive at baseline.