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)

NCT03071094 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: TG6006.01
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (3)

• Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)

  DLTs are occurrence of any following AE related to study drugs occurring during 4 weeks after 1st Pexa-Vec injection: 1. Grade 3-4 non-hematologic toxicity representing a 2-grade increase over baseline, excluding: nausea, vomiting, diarrhea, fever\>40.0°C lasting less than 24h (grade 3), alopecia, grade 3 fatigue\* and grade 3 laboratory/metabolic abnormalities\* (\*returning to grade 2 or less within 72h) 2. Grade ≥ 3 acute immune-related AE involving major organs 3. Grade ≥ 3 injection site reaction 4. AST or ALT ≥ 10xULN unless related to liver metastases progression; AST or ALT doubling concurrent with total bilirubin doubling 5. Any toxicity resulting in treatment delay of 2 or more weeks 6. Grade ≥ 3 or ≥ 2-grade neutropenia increase over baseline lasting \>7 days, neutropenic fever, grade 4 thrombocytopenia (or grade 3 with bleeding) 7. Association of LVEF less than LLN, blood troponin T or I increase above ULN and any ECG abnormality indicating grade 3 cardiac disorder.

  4 weeks from the first study drug administration

• Phase I: Number of Participants With Serious Adverse Events (SAEs)

  A Serious Adverse Event (SAE) is defined as any untoward medical occurrence or effect in a patient, whether or not considered related to the protocol treatment, that at any dose: (i) results in death, (ii) is life-threatening, (iii) requires inpatient's hospitalization or prolongation of existing inpatients´ hospitalization, (iv) results in persistent or significant disability or incapacity, (v) is a congenital anomaly or birth defect, (vi) results in any other medically important condition.

  4 weeks from the first study drug administration

• Overall Response Rate (ORR) According to RECIST 1.1.

  Overall Response Rate (ORR): proportion of patients, whose best overall response is either complete response (CR) or partial response (PR), confirmed at least 4 weeks after initial documentation.

  6 months from the first study drug administration

Study Arms (2)

Pexa-Vec combined with Nivolumab - Phase I

EXPERIMENTAL

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).

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

Pexa-Vec combined with Nivolumab - Phase IIa

EXPERIMENTAL

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).

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

Interventions

Pexastimogene Devacirepvec (Pexa Vec) BIOLOGICAL

Pexa-Vec (pexastimogene devacirepvec) will be administered as 3 bi-weekly intratumoral (IT) injections of 10\^9 pfu at day 1 and weeks 2 and 4

Pexa-Vec combined with Nivolumab - Phase I; Pexa-Vec combined with Nivolumab - Phase IIa

Nivolumab DRUG

Nivolumab will be administered intravenously every 2 weeks (from week 2)

Pexa-Vec combined with Nivolumab - Phase I; Pexa-Vec combined with Nivolumab - Phase IIa

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Transgene: lead

Study Sites (2)

Site No 0102

Nancy, France

Location

Site No 0101

Paris, France

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study was terminated prematurely as per Sponsor's decision based on the failure of Pexa-Vec and nivolumab in their respective pivotal trials in HCC. As a consequence, the enrollment in Phase IIa was not completed.

Results Point of Contact

• Title: Associate Medical Director
• Organization: Transgene

clinical.trials@transgene.fr

+ 33 (0)3 88 27 91 00

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2017
• First Posted: March 6, 2017
• Study Start: July 27, 2017
• Primary Completion: September 30, 2020
• Study Completion: February 3, 2021
• Last Updated: November 19, 2021
• Results First Posted: November 19, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)