Hepatocellular Carcinoma Study Comparing Vaccinia Virus Based Immunotherapy Plus Sorafenib vs Sorafenib Alone
A Phase 3 Randomized, Open-Label Study Comparing Pexa Vec (Vaccinia GM CSF / Thymidine Kinase-Deactivated Virus) Followed by Sorafenib Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC) Without Prior Systemic Therapy
  • Phase

    Phase 3
  • Study Type

  • Study Participants

This is a randomized Phase 3 study to determine whether treatment with vaccinia virus based immunotherapy (Pexa-Vec) followed by sorafenib increases survival compared to treatment with sorafenib in patients with advanced hepatocellular carcinoma who have not received prior systemic therapy.
This is a multi-center, randomized, open-label, Phase 3 study comparing Pexa Vec followed by sorafenib versus sorafenib in patients with advanced HCC without prior systemic therapy.

A total of 459 patients were randomly assigned to 2 treatment arms- 234 patients in the Pexa-Vec followed by sorafenib treatment group and 225 patients in the sorafenib only treatment group.
Study Started
Oct 31
Primary Completion
Jul 31
Study Completion
Jul 31
Results Posted
Dec 16
Last Update
Dec 16

Biological Pexastimogene Devacirepvec (Pexa Vec)

Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells.

  • Other names: JX-594

Drug Sorafenib

Sorafenib belongs to the pharmacotherapeutic group of antineoplastic agents, protein kinase inhibitors, ATC code: L01XE05. Sorafenib is a multi-kinase inhibitor which has demonstrated both anti-proliferative and anti-angiogenic properties in vitro and in vivo. Sorafenib is approved for the treatment of advanced HCC and is the Standard Of Care for this disease.

  • Other names: Nexavar

Pexa-Vec followed by Sorafenib Experimental

Pexa-Vec (pexastimogene devacirepvec) will be administered as 3 bi-weekly intratumoral (IT) injections of 1e9 pfu at day 1 and weeks 2 and 4, followed by sorafenib at Week 6.

Sorafenib Active Comparator

Sorafenib (400 mg twice daily) begins on Day 1.


Inclusion Criteria:

Histological/cytological diagnosis of primary HCC
Advanced stage HCC (Barcelona Clinic Liver Cancer [BCLC] Stage C or B per American Association for the Study of Liver Disease [AASLD] guidelines)
At least one measurable viable tumor in the liver, ≥1 cm longest diameter (LD), using a dynamic imaging technique (arterial phase of triphasic computerized tomography [CT] scan, or dynamic contrast-enhanced magnetic resonance imaging [MRI]), and injectable under imaging-guidance (CT and/or ultrasound)
Child-Pugh Class A
Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
Adequate hematological, hepatic, and renal function:
Additional inclusion criteria exist

Exclusion Criteria:

Histological diagnosis of cholangiocarcinoma, hepatocholangiocarcinoma, fibrolamellar carcinoma and hepatoblastoma
Symptomatic cardiovascular disease, including but not limited to significant coronary artery disease (e.g., requiring angioplasty or stenting) or congestive heart failure within the preceding 12 months
Current or past history of cardiovascular disease (e.g.. past history of myocardial infarction, ischemic cardiomyopathy) unless cardiology consultation and clearance has been obtained for study participation
History of moderate or severe ascites, bleeding esophageal varices, hepatic encephalopathy or pleural effusions related to liver insufficiency within 6 months of screening
Bulky disease patients - tumors encompassing >50% of the liver volume and / or inferior vena cava invasion
Known significant immunodeficiency due to underlying illness (e.g., HIV/AIDS) and/or immune-suppressive medication including high-dose corticosteroids
Ongoing severe inflammatory skin condition (as determined by the Investigator) requiring medical treatment
History of severe eczema (as determined by the Investigator) requiring medical treatment
Additional exclusion criteria exist


Pexa-Vec Followed by Sorafenib


All Events

Event Type Organ System Event Term Pexa-Vec Followed by Sorafenib Sorafenib

Overall Response Rate (ORR)

Percentage of participants who showed overall response during their participation in the study. Per Modified Response Evaluation Criteria In Solid Tumors Criteria (mRECIST) and assessed by tri-phasic contrast enhanced CT: Complete Response (CR), Disappearance of intratumoral enhancing area; Partial Response (PR), >=30% decrease in the sum of the diameters of enhancing area; Overall Response (OR) = CR + PR.


percentage of participants

Pexa-Vec Followed by Sorafenib

percentage of participants



Age, Continuous

years (Mean)
Standard Deviation: 10.55

Age, Categorical

ECOG performance status

Ethnicity (NIH/OMB)

Region of Enrollment

Sex: Female, Male

Overall Study

Pexa-Vec Followed by Sorafenib