Biodistribution, shedding, and transmissibility of the oncolytic virus talimogene laherparepvec in patients with melanoma.

Biodistribution, shedding, and transmissibility of the oncolytic virus talimogene laherparepvec in patients with melanoma.

Publication date: Aug 10, 2019

Talimogene laherparepvec (T-VEC) is an intralesionally delivered, modified herpes simplex virus type-1 oncolytic immunotherapy. The biodistribution, shedding, and potential transmission of T-VEC was systematically evaluated during and after completion of therapy in adults with advanced melanoma.

In this phase 2, single-arm, open-label study, T-VEC was administered into injectable lesions initially at 10 plaque-forming units (PFU)/mL, 10 PFU/mL 21 days later, and 10 PFU/mL every 14 (+/-3) days thereafter. Injected lesions were covered with occlusive dressings for ≥1 week. Blood, urine, and swabs from exterior of occlusive dressings, surface of injected lesions, oral mucosa, anogenital area, and suspected herpetic lesions were collected throughout the study. Detectable T-VEC DNA was determined for each sample type; infectivity was determined for all swabs with detectable T-VEC DNA.

Sixty patients received ≥1 dose of T-VEC. During cycles 1-4, T-VEC DNA was detected in blood (98.3% of patients, 36.7% of samples), urine (31.7% of patients, 3.0% of samples) and swabs from injected lesions (100% of patients, 57.6% of samples), exterior of dressings (80% of patients,19.5% of samples), oral mucosa (8.3% of patients, 2.5% of samples), and anogenital area (8.0% of patients, 1.1% of samples). During the safety follow-up period, T-VEC DNA was only detected on swabs from injected lesions (14% of patients, 5.8% of samples). T-VEC DNA was detected in 4/37 swabs (3/19 patients) of suspected herpetic lesions. Among all samples, only those from the surface of injected lesions tested positive for infectivity (8/740 [1.1%]). Three close contacts reported signs and symptoms of suspected herpetic origin; however, no lesions had detectable T-VEC DNA.

Using current guidelines, T-VEC can be administered safely to patients with advanced melanoma and is unlikely to be transmitted to close contacts with appropriate use of occlusive dressings. FUND: This study was funded by Amgen Inc.: ClinicalTrials.gov, NCT02014441.

Andtbacka, R.H.I., Amatruda, T., Nemunaitis, J., Zager, J.S., Walker, J., Chesney, J.A., Liu, K., Hsu, C.P., Pickett, C.A., and Mehnert, J.M. Biodistribution, shedding, and transmissibility of the oncolytic virus talimogene laherparepvec in patients with melanoma. 23750. 2019 EBioMedicine.

Concepts Keywords
Amgen Melanoma
Blood Herpes
DNA Immunotherapy
Herpes Simplex Virus Medicine
Immunotherapy Experimental cancer treatments
Melanoma Virotherapy
Oncolytic Life sciences
Oncolytic Virus Biotechnology
Oral Mucosa Clinical medicine
Urine Talimogene laherparepvec
Oncolytic virus
Melanoma
Herpes simplex virus
Del

Semantics

Type Source Name
drug DRUGBANK Dihydrotachysterol
disease DOID herpes simplex
disease MESH herpes simplex
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
drug DRUGBANK Talimogene laherparepvec

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