Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antibodies

Immunomodulating Agents

Immunoglobulins

Antibodies, Blocking

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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).

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

Pexastimogene Devacirepvec (Pexa Vec)

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

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).

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 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)

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.

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

Transgene

Adverse event information was collected by regular investigator assessment and regular laboratory testing.

Pexa-Vec Combined With Nivolumab - Phase I

Pexa-Vec Combined With Nivolumab - Phase IIa

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

As per the BCLC (Barcelona Clinic Liver Cancer) scale, the liver cancer stages range from stage 0 (less advanced stage of liver cancer) to stage D (more advanced stage of liver cancer):

* Stage 0: very early stage of liver cancer, single nodule \<2cm
* Stage A: early stage of liver cancer, single nodule \<5cm or up to 3 nodules \<3cm
* Stage B: intermediate stage of liver cancer, large multinodular
* Stage C: advanced stage of liver cancer, portal invasion / extrahepatic spread
* Stage D: terminal stage of liver cancer.

Stage of HCC per BCLC (Barcelona Clinic Liver Cancer)

As per the ECOG (Eastern Cooperative Oncology Group) scale, the performance status is ranked from grade 0 (best performance status) to grade 4 (worst performance status) as follows:

* Grade 0: fully active
* Grade 1: restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature
* Grade 2: ambulatory and capable of all selfcare but unable to carry out any work activities
* Grade 3: capable of only limited selfcare
* Grade 4: completely disabled.

ECOG (Eastern Cooperative Oncology Group) performance status

Phase I and Phase IIa: Participants who received at least one dose of either study drug.

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.

Associate Medical Director

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).

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

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

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

Pexa-Vec Combined With Nivolumab - Phase I and Phase IIa

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.

Spots Global Cancer Trial Database for 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)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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