The purpose of this pilot safety study is to evaluate the safety and tolerability of JX-594 (Pexa-Vec) administered intravenously and intratumorally prior to standard sorafenib therapy.
This is a Phase 2, open-label, pilot safety study designed to evaluate the safety and tolerability of sequential therapy consisting of Pexa-Vec (JX-594) followed by standard sorafenib in patients with advanced, unresectable primary hepatocellular carcinoma (HCC). Patients will receive an initial intravenous (IV) infusion of Pexa-Vec at a dose of 1 x 10\^9 plaque-forming units (pfu) on Day 1. This is followed by two intratumoral (IT) injections of Pexa-Vec on Day 8 and Day 22, each at a total dose of 1 x 10\^9 pfu divided among 1 to 5 hepatic tumors. Starting on Day 25 (approximately 3 days after the final regular dose of Pexa-Vec), patients will initiate standard oral sorafenib therapy twice daily. For patients with viable hepatic tumor tissue at Week 12, an optional additional IT dose of Pexa-Vec may be administered. The primary objective of this study is to assess the safety and toxicity of this sequential regimen, determined by the incidence of treatment-related Grade 3 and Grade 4 adverse events (AEs) and treatment-related serious adverse events (SAEs). Secondary objectives include evaluating the disease control rate (DCR) at 12 weeks, overall survival (OS) time, and radiographic response rate based on modified RECIST (mRECIST 1.0) and/or Choi criteria.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Patients will receive a total dose of 1e9 pfu per treatment starting with one IV dose on Day 1 and injected intratumorally in 1-5 intrahepatic tumors on Day 8 and 22. An optional maintenance JX-594 dose may be given intratumorally at Week 12.
Starting on Day 25 (3 days after the final JX-594 dose), patients will initiate oral sorafenib therapy twice daily according to standard approved guidelines. Sorafenib therapy is briefly interrupted if an optional Week 12 JX-594 dose is given.
Pusan National University Hospital
Busan, South Korea
Pusan National University Yangsan Hospital
Yangsan, South Korea
Number of Participants With Treatment-Related Grade 3 and Grade 4 Adverse Events (AEs) and Serious Adverse Events (SAEs)
Safety and toxicity will be determined by the incidence of treatment-related Grade 3 and Grade 4 AEs and treatment-related SAEs. Adverse events will be collected and assessed through 28 days after the last dose of JX-594 (or until all events considered probably or possibly related to JX-594 have resolved, stabilized, or returned to baseline status).
Time frame: Safety evaluations through 28 days after last dose of JX-594
Number of Participants Achieving Disease Control (DCR) at 12 Weeks
Disease Control Rate (DCR) is defined as the percentage of participants achieving a confirmed complete response (CR), partial response (PR), or stable disease (SD), with tumor responses assessed based on modified RECIST (mRECIST 1.0) and/or Choi criteria. Per mRECIST 1.0 for target tumors, CR indicates the disappearance of all tumor(s), PR indicates a \>=30% decrease in the sum of the longest diameters (LD) of tumor(s) referenced to Baseline, and SD represents any case that does not qualify for either PR or progressive disease (PD, which is a \>=20% increase in the sum of LDs). Additionally, per Choi criteria, a response is defined as a \>=10% decrease in the LD of the tumor and/or a \>=15% decrease in the average tumor density measured in Hounsfield Units on a CT scan.
Time frame: 12 weeks from first JX-594 dose
Determine Radiographic Response Rate
Response rate evaluation based on modified RECIST and/or Choi response criteria
Time frame: Periodically throughout study participation (average of up to 1 year)
Overall Survival (OS)
Overall survival (OS) is defined as the time from the first dose of Pexa-Vec treatment until death from any cause. For patients not known to have died at the time of the analysis, OS was censored on the date they were last known to be alive. Data were summarized using the Kaplan-Meier method.
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Time frame: From the date of first treatment until death from any cause, assessed up to approximately 40 months.