Hepatocellular Carcinoma (HCC)Phase 1/2NCT03071094

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)

A Phase 1/2 study testing Pexastimogene Devacirepvec (Pexa Vec) and Nivolumab in people with Hepatocellular Carcinoma (HCC), run by Transgene at 2 sites in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hepatocellular Carcinoma (HCC)
What is being tested?: Pexastimogene Devacirepvec (Pexa Vec) and Nivolumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 14 participants
Where: 2 sitesFrance
Study dates: 27 Jul 2017to 3 Feb 2021
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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)

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Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
Adequate hematological, hepatic, and renal function
Additional inclusion criteria exist

Who cannot join

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 locations and contacts

2 sites in 1 country.

France2 sites

Site No 0102
Nancy
Site No 0101
Paris

Other trials in France

About this study

Official title: A Phase I/IIa 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)

Conditions: Hepatocellular Carcinoma (HCC)
Being tested: Pexastimogene Devacirepvec (Pexa Vec), Nivolumab
Medical subject headings: Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT03071094
Study group	Role	What they receive
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). Receives: 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). Receives: Biological: Pexastimogene Devacirepvec (Pexa Vec); Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 6 months from the first study drug administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Jul 20173 Feb 2021

First posted6 Mar 2017
Study start27 Jul 2017
Primary completion30 Sep 2020
Study completion3 Feb 2021

Why it stopped: The decision was taken to stop prematurely the trial due to the failure of Pexa-Vec and nivolumab in their respective pivotal trials (i.e., PHOCUS and CheckMate 459).

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03071094
Sponsor's protocol ID: TG6006.01
Status last verified: Oct 2021
First submitted: 10 Feb 2017
Last updated: 19 Nov 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Hepatocellular Carcinoma (HCC) trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/IIa 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)
ClinicalTrials.gov ID: NCT03071094
Acronym / sponsor ID: TG6006.01
Conditions: Hepatocellular Carcinoma (HCC)
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: The decision was taken to stop prematurely the trial due to the failure of Pexa-Vec and nivolumab in their respective pivotal trials (i.e., PHOCUS and CheckMate 459).
Enrolment: 14 participants (actual)
Lead sponsor: TransgeneIndustry (pharma, biotech, devices)
Study start: 27 Jul 2017 (actual)
Primary completion: 30 Sep 2020 (actual)
Study completion: 3 Feb 2021 (actual)
First posted: 6 Mar 2017 (actual)
Results: Posted 19 Nov 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Pexa-Vec combined with Nivolumab - Phase I	Experimental	Biological: Pexastimogene Devacirepvec (Pexa Vec), Drug: NivolumabParticipants 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).
Pexa-Vec combined with Nivolumab - Phase IIa	Experimental	Biological: Pexastimogene Devacirepvec (Pexa Vec), Drug: NivolumabParticipants 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).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

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

Key exclusion criteria (8 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Pexastimogene Devacirepvec (Pexa Vec)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	Biological	Pexa-Vec combined with Nivolumab - Phase I, Pexa-Vec combined with Nivolumab - Phase IIa
NivolumabNivolumab will be administered intravenously every 2 weeks (from week 2)	Drug	Pexa-Vec combined with Nivolumab - Phase I, Pexa-Vec combined with Nivolumab - Phase IIa

Primary outcome

Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: 4 weeks from the first study drug administration
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.
Phase I: Number of Participants With Serious Adverse Events (SAEs)
Time frame: 4 weeks from the first study drug administration
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.
Overall Response Rate (ORR) According to RECIST 1.1.
Time frame: 6 months from the first study drug administration
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.

Results and safety

Results posted to the registry on 19 Nov 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Pexa-Vec Combined With Nivolumab - Phase I	7	5
Pexa-Vec Combined With Nivolumab - Phase IIa	5	4

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

Time frame: 4 weeks from the first study drug administration. Count of participants. Unit: Participants

Measure	Pexa-Vec Combined With Nivolumab - Phase I n = 6
Value	0

Population analysed: Participants who received at least one dose of either study drug (excluding one patient who did not complete the 4 week-period from the first study drug administration).

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

Time frame: 4 weeks from the first study drug administration. Count of participants. Unit: Participants

Measure	Pexa-Vec Combined With Nivolumab - Phase I n = 7
Value	6

Population analysed: Participants who received at least one dose of either study drug.

Primary outcome: Overall Response Rate (ORR) According to RECIST 1.1.

Time frame: 6 months from the first study drug administration. Number (95% Confidence Interval). Unit: Percentage of participants

Measure	Pexa-Vec Combined With Nivolumab - Phase I and Phase IIa n = 12
Value	33.3 (9.9 to 65.1)

Population analysed: The overall response rate (ORR) was calculated on the total number of participants included in Phase I and Phase IIa who received at least one dose of either study drug. Phase I and IIa patients did not differ in terms of eligibility criteria and study treatment and represented a total of 12 patients. Thus a single analysis of the ORR on the phase I/IIa sample size is more relevant than two separate analyses on very low sample sizes.

Adverse events

Time frame: Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Pexa-Vec Combined With Nivolumab - Phase I	6 of 7 (85.7%)	7 of 7 (100%)	1 of 7
Pexa-Vec Combined With Nivolumab - Phase IIa	4 of 5 (80%)	5 of 5 (100%)	1 of 5

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Pexastimogene Devacirepvec (Pexa Vec) and Nivolumab in people with Hepatocellular Carcinoma (HCC), run by Transgene at 2 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I: Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: 4 weeks from the first study drug administration). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03071094.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2021.