A phase I dose-escalation study of intratumoral herpes simplex virus-1 mutant HSV1716 in pediatric/young adult patients with refractory non-central nervous system solid tumors.

10047 Background: HSV1716 is a mutant herpes simplex virus type 1 deleted in the RL1 gene which encodes the protein ICP34.5, a specific determinant of virulence. Mutants lacking the RL1 gene are capable of replication in actively dividing cells but not in terminally differentiated cells – a phenotype exploited to selectively kill tumor cells. Studies in adult patients with high grade glioma, melanoma and squamous cell carcinoma report that HSV1716 is safe when administered by intra-tumoral injection. This is the first study of HSV1716 in pediatric/young adult patients. Methods: The primary endpoint of the study is to assess safety of intratumoral HSV1716 in pediatric/young adult patients, and to determine any dose-limiting toxicities (DLT) at the doses given. Patients undergo long-term follow up in accordance with FDA guidelines for viral vectors. The secondary endpoints of the study are to measure: (i) antiviral immune response; (ii) systemic viremia and viral shedding and (iii) the antitumor activity of HSV1716 by radiological response within the confines of a Phase I study. Patients aged 7 to 30 with solid non-CNS tumors refractory to standard therapy (or for which no therapy exists) are eligible for the study provided the target lesion is accessible to image-guided injection. Eligible patients receive a single dose of HSV1716 (Virttu Biologics Limited) at either 105 or 2x106 plaque forming units (pfu) HSV1716 administered directly into the tumor via ultrasound or CT-guided injection by an interventional radiologist. Tumor response between baseline and day 28 is assessed by modified RECIST criteria. Patients showing at least stable disease may receive up to a 3 additional doses of HSV1716. Results: Recruitment of the first cohort of 3 patients has been completed without DLT or procedure related severe adverse events. In the second cohort, 2 patients have been treated without DLT or procedure related SAE. Conclusions: The trial is in progress and the study is open to recruitment. Clinical trial information: NCT00931931.