A Trial to Evaluate the Safety and Efficacy of the Combination of the Oncolytic Immunotherapy Pexa-Vec With the PD-1 Receptor Blocking Antibody Nivolumab in the First-line Treatment of Advanced Hepatocellular Carcinoma (HCC)

Transgene

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Hepatocellular Carcinoma (HCC)

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT03071094

TG6006.01

Details and patient eligibility

About

This is a study to Evaluate the Safety and Efficacy of the Combination of the Oncolytic Immunotherapy Pexa-Vec With the PD-1 Receptor Blocking Antibody Nivolumab in the First-line Treatment of Advanced Hepatocellular Carcinoma (HCC).

Enrollment: 14 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histological/cytological diagnosis of primary HCC, excluding cholangiocarcinoma, hepatocholangiocarcinoma, fibrolamellar carcinoma and hepatoblastoma
• Advanced stage HCC per EASL-EORTC (European Association for the Study of the Liver-European Organisation for Research and Treatment of Cancer) guidelines, i.e. patients who are not candidates for curative interventions and not candidates for locoregional modalities
• Patients naïve to systemic therapy for HCC
• Tumor status (as determined by radiology evaluation): 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 or ultrasound)
• At least one tumor that has not received prior local-regional treatment, or that has exhibited definitive growth of viable tumor since prior local-regional treatment of HCC undertaken at least 4 weeks prior to enrolment or 3 months prior to enrolment for radioembolization
• Child-Pugh Class A. Note: paracentesis, albumin infusion or diuretic treatment cannot be used to downgrade Child-Pugh score (e.g., to improve from severe to moderate/mild or from moderate to mild ascites)
• 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; patients with adequately treated esophageal varices are allowed
• Active, known or suspected significant immunodeficiency due to underlying illness including HIV/AIDS, autoimmune diseases, and/or immune-suppressive medication including high-dose corticosteroids
• History of severe eczema and/or ongoing severe inflammatory skin condition (as determined by the Investigator) requiring medical treatment
• Any known allergy or reaction to any component of nivolumab formulation or its excipients
• Additional exclusion criteria exist

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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14 participants in 2 patient groups

Pexa-Vec combined with Nivolumab - Phase I

Experimental group

Description:

Participants were administered Pexa-Vec (pexastimogene devacirepvec) as 3 bi-weekly intratumoral (IT) injections of 10\^9 pfu at day 1 and weeks 2 and 4 and nivolumab intravenously every 2 weeks (from week 2).

Treatment:

Drug: Nivolumab

Biological: Pexastimogene Devacirepvec (Pexa Vec)

Pexa-Vec combined with Nivolumab - Phase IIa

Experimental group

Description:

Participants were administered Pexa-Vec (pexastimogene devacirepvec) as 3 bi-weekly intratumoral (IT) injections of 10\^9 pfu at day 1 and weeks 2 and 4 and nivolumab intravenously every 2 weeks (from week 2).

Treatment:

Drug: Nivolumab

Biological: Pexastimogene Devacirepvec (Pexa Vec)