Hepatocellular Carcinoma Study Comparing Vaccinia Virus Based Immunotherapy Plus Sorafenib vs Sorafenib Alone (PHOCUS)

SillaJen

Status and phase: Completed; Phase 3

Conditions: Hepatocellular Carcinoma (HCC)

Treatments: Biological: Pexastimogene Devacirepvec (Pexa Vec); Drug: Sorafenib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02562755

JX594-HEP024

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 459 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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459 participants in 2 patient groups

Pexa-Vec followed by Sorafenib

Experimental group

Description:

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.

Treatment:

Drug: Sorafenib

Biological: Pexastimogene Devacirepvec (Pexa Vec)

Sorafenib

Active Comparator group

Description:

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

Treatment:

Drug: Sorafenib