First-in-Human Intravenous Seprehvir in Young Cancer Patients: A Phase 1 Clinical Trial

Area of Science:

• Oncology
• Virology
• Gene Therapy

Background:

• Seprehvir (HSV1716), an oncolytic herpes simplex virus-1 (HSV-1), has shown safety in pediatric intratumoral administration.
• Systemic administration safety for Seprehvir in pediatric oncology remains unexplored.

Purpose of the Study:

• To evaluate the safety and tolerability of intravenous Seprehvir in pediatric patients with relapsed or refractory extra-cranial solid cancers.
• To assess viral replication, shedding, and anti-tumor effects following systemic Seprehvir administration.

Main Methods:

• A Phase I, first-in-human trial involving intravenous administration of Seprehvir at two dose levels (5 × 10⁴ iu/kg or 2.5 × 10⁵ iu/kg).
• Monitoring of adverse events, tumor response via imaging, HSV-1 serology, and detection of viremia and shedding using PCR and culture.
• Seven patients received a single dose, and two patients received multiple doses.

Main Results:

• No dose-limiting toxicities were observed in any of the nine participating patients.
• All five HSV-1 seronegative patients developed antibodies (seroconverted) by day 28.
• HSV-1 DNA was detected in the peripheral blood of four patients, indicating de novo virus replication. Two patients achieved stable disease.

Conclusions:

• Intravenous Seprehvir is well-tolerated in children and young adults with late-stage cancer, with no observed viral shedding.
• Viremia suggests potential for future studies involving higher Seprehvir doses or combination therapies for enhanced anti-cancer efficacy.