A Phase 2b Study of Modified Vaccinia Virus to Treat Patients Advanced Liver Cancer Who Failed Sorafenib (TRAVERSE)

• Time to Tumor Progression [ Time Frame: CT scan every six weeks until progression or death, assessed up to 21 months ] [ Designated as safety issue: No ]
  Determine time-to-tumor-progression (TTP) for Arm A compared with Arm B based on mRECIST for HCC.
• Quality of Life [ Time Frame: assessed up to 21 months (average) ] [ Designated as safety issue: No ]
  Determine the Quality of Life (QoL) of patients treated in Arm A compared with Arm B.
• Tumor Response [ Time Frame: CT scan every 6 weeks until progression or death, assessed up to 21 months (average) ] [ Designated as safety issue: No ]
  Determine tumor response based on mRECIST for HCC of Arm A versus Arm B
• Safety profile of JX594 [ Time Frame: assessed up to 21 months (average) ] [ Designated as safety issue: Yes ]
  Safety will be assessed by the number of adverse events (AEs) and serious adverse events (SAEs)
• Time-to-symptomatic-progression [ Time Frame: assessed up to 21 months (average) ] [ Designated as safety issue: No ]
  Determine time to progression of Arm A compared to Arm B.

• Time to Tumor Progression [ Time Frame: CT scan every six weeks until progression or death, assessed up to 21 months ] [ Designated as safety issue: No ]
  Determine time-to-tumor-progression (TTP) for Arm A compared with Arm B based on mRECIST for HCC.
• Quality of Life [ Time Frame: assessed up to 21 months (average) ] [ Designated as safety issue: No ]
  Determine the Quality of Life (QoL) of patients treated in Arm A compared with Arm B.
• Tumor Response [ Time Frame: CT scan every 6 weeks until progression or death, assessed up to 21 months (average) ] [ Designated as safety issue: No ]
  Determine tumor response based on mRECIST for HCC of Arm A verus Arm B
• Safety profile of JX594 [ Time Frame: assessed up to 21 months (average) ] [ Designated as safety issue: Yes ]
  Safety will be assessed by the number of adverse events (AEs) and serious adverse events (SAEs)
• Time-to-symptomatic-progression [ Time Frame: assessed up to 21 months (average) ] [ Designated as safety issue: No ]
  Determine time to progression of Arm A compared to Arm B.

This study is to determine whether JX-594 (Pexa-Vec) plus best supportive care is more effective in improving survival than best supportive care in patients with advanced Hepatocellular Carcinoma (HCC) who have failed sorafenib.

• Hepatocellular Carcinoma
• Liver Cancer
• HCC

• Biological: JX-594 recombinant vaccina GM-CSF
  Patients will be randomised 2:1 to Arm A or Arm B and will receive 6 treatments on days 1, 8, 22, week 6, week 12, and week 18 plus best supportive care as needed.
• Other: Best Supportive Care
  Patients will be randomised 2:1 to Arm A or Arm B and will receive best supportive care as needed.

• Experimental: Arm A
  Patients on Arm A will receive 1 e9 pfu (plaque forming units) total dose of JX-594 (Vaccinia GM-CSF / TK-deactivated Virus) on each of six (6) treatments over 18 weeks.
  Intervention: Biological: JX-594 recombinant vaccina GM-CSF
• Arm B
  Patients on the control arm (Arm B) will have best supportive care over 18 weeks.
  Intervention: Other: Best Supportive Care

KEY Inclusion Criteria:

• Diagnosis of primary HCC by tissue biopsy (histological/cytological diagnosis), or clinical diagnosis
• Previously treated with sorafenib for ≥ 14 days and has discontinued sorafenib treatment at least 14 days prior to randomization due to either intolerance or radiographic progression NOTE: Sorafenib is NOT required to be the most recent treatment received for HCC
• ECOG performance status 0, 1 or 2
• Child-Pugh Class A; or Child-Pugh Class B7 without clinically significant ascites
• Hematocrit ≥30% or Hemoglobin ≥10 g/dL
• Tumor status: Measurable viable tumor in the liver and injectable under imaging-guidance; At least one tumor in the liver that has not received prior local-regional treatment OR that has exhibited >25% growth in viable tumor size since prior local-regional treatment.

KEY Exclusion Criteria:

• Received sorafenib within 14 days prior to randomization
• Received systemic anti-cancer therapy other than sorafenib within 28 days of randomization
• Prior treatment with JX-594
• Platelet count < 50,000 PLT/ mm3
• Total white blood cell count < 2,000 cells/mm3
• Prior or planned organ transplant
• Known significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication
• Severe or unstable cardiac disease
• Viable CNS malignancy associated with clinical symptoms
• Pregnant or nursing an infant
• History of inflammatory skin condition (e.g., eczema requiring previous treatment, atopic dermatitis)