Phase 1 Study of Intratumoral Pexa-Vec (JX-594), an Oncolytic and Immunotherapeutic Vaccinia Virus, in Pediatric Cancer Patients

Abstract

Pexa-Vec (pexastimogene devacirepvec, JX-594) is an oncolytic and immunotherapeutic vaccinia virus designed to destroy cancer cells through viral lysis and induction of granulocyte-macrophage colony-stimulating factor (GM-CSF)-driven tumor-specific immunity. Pexa-Vec has undergone phase 1 and 2 testing alone and in combination with other therapies in adult patients, via both intratumoral and intravenous administration routes. We sought to determine the safety of intratumoral administration in pediatric patients. In a dose-escalation study using either 10(6) or 10(7) plaque-forming units per kilogram, we performed one-time injections in up to three tumor sites in five pediatric patients and two injections in one patient. Ages at study entry ranged from 4 to 21 years, and their cancer diagnoses included neuroblastoma, hepatocellular carcinoma, and Ewing sarcoma. All toxicities were ≤ grade 3. The most common side effects were sinus fever and sinus tachycardia. All three patients at the higher dose developed asymptomatic grade 1 treatment-related skin pustules that resolved within 3-4 weeks. One patient showed imaging evidence suggestive of antitumor biological activity. The two patients tested for cellular immunoreactivity to vaccinia antigens showed strong responses. Overall, our study suggests Pexa-Vec is safe to administer to pediatric patients by intratumoral administration and could be studied further in this patient population.

Intratumoral Injection of HSV1716, an Oncolytic Herpes Virus, Is Safe and Shows Evidence of Immune Response and Viral Replication in Young Cancer Patients

“…The fact that an uninjected lesion also transiently flared on PET may indicate that localized HSV1716 infection had a systemic antitumor immune effect. Two non-pathogenic wild-type oncolytic viruses (seneca valley virus and reovirus), and one attenuated pathogenic virus (vaccinia virus), have also been studied in children and showed few toxicities but little evidence of disease response (19)(20)(21). Of these and the current pediatric trials, this trial using HSV1716 and the trial using vaccinia virus utilized intratumoral virus administration, whereas the other 2 trials used intravenous or systemic administration.…”

Polymeric Cups for Cavitation-mediated Delivery of Oncolytic Vaccinia Virus

“…1,2 The next decade is likely to see a wide range of these agents continuing their progression through the clinical testing pathway both in combination with conventional anticancer strategies 3 and immuno-oncology approaches. 4 However, the poor delivery of OV into and throughout target tumors following systemic administration means that, to date, the majority of clinical applications are reliant on direct intratumoral injection, a route which is inefficient 5 and restricts the type of cancer which can be treated.…”

OMICS Approach for Identifying Predictive Biomarkers in Osteosarcoma

“…In addition, there are also several possible immunotherapies for osteosarcoma. Cripe et al reported the possible application of treatment with a vaccinia virus, pexastimogene devacirepvec, through viral lysis and induction of granulocyte macrophage colony-stimulating factor-driven tumor-speciic immunity in osteosarcoma [41]. Tsukahara et al demonstrated the possibility of peptide therapy in osteosarcoma [42].…”