Trial Outcomes & Findings 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) (NCT NCT03071094)

Last Updated: 2021-11-19

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

14 participants

Primary outcome timeframe

4 weeks from the first study drug administration

Results posted on

2021-11-19

Participant Flow

First participant signed informed consent on 04 July 2017. Last participant last visit occurred on 03 February 2021.

Of 14 screened participants, 12 met eligibility criteria and were included in the trial. This was a Phase I/IIa trial with Phase I: single cohort of 6 patients assessing the safety of standard Pexa-Vec and nivolumab doses and Phase IIa: extension of the Phase I to up to 30 patients, assessing the efficacy and safety of Pexa-Vec and nivolumab. The trial was terminated prematurely during the Phase IIa due to the failure of Pexa-Vec and nivolumab in their respective pivotal trials in HCC.

Participant milestones

Participant milestones
Measure	Pexa-Vec Combined With Nivolumab - Phase I 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 Combined With Nivolumab - Phase IIa 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).
Overall Study STARTED	7	5
Overall Study COMPLETED	5	4
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Pexa-Vec Combined With Nivolumab - Phase I 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 Combined With Nivolumab - Phase IIa 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).
Overall Study Death	1	1
Overall Study Adverse Event	1	0

Baseline Characteristics

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)

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 4 weeks from the first study drug administration

Population: 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).

Outcome measures

Outcome measures
Measure	Pexa-Vec Combined With Nivolumab - Phase I n=6 Participants 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).
Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants

PRIMARY outcome

Timeframe: 4 weeks from the first study drug administration

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

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.

Outcome measures

Outcome measures
Measure	Pexa-Vec Combined With Nivolumab - Phase I n=7 Participants 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).
Phase I: Number of Participants With Serious Adverse Events (SAEs)	6 Participants

PRIMARY outcome

Timeframe: 6 months from the first study drug administration

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Pexa-Vec Combined With Nivolumab - Phase I n=12 Participants 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).
Overall Response Rate (ORR) According to RECIST 1.1.	33.3 Percentage of participants Interval 9.9 to 65.1

Adverse Events

Pexa-Vec Combined With Nivolumab - Phase I

Serious events: 6 serious events

Other events: 7 other events

Deaths: 1 deaths

Pexa-Vec Combined With Nivolumab - Phase IIa

Serious events: 4 serious events

Other events: 5 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Pexa-Vec Combined With Nivolumab - Phase I n=7 participants at risk 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 Combined With Nivolumab - Phase IIa n=5 participants at risk 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).
General disorders Pyrexia	28.6% 2/7 • Number of events 3 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.	0.00% 0/5 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.
General disorders Influenza Like Illness	14.3% 1/7 • Number of events 2 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.	0.00% 0/5 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.
General disorders General Physical Health Deterioration	14.3% 1/7 • Number of events 1 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.	20.0% 1/5 • Number of events 1 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.
General disorders Inflammation	0.00% 0/7 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.	20.0% 1/5 • Number of events 1 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.
Infections and infestations Device Related Infection	14.3% 1/7 • Number of events 1 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.	0.00% 0/5 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Diabetic Ketoacidosis	14.3% 1/7 • Number of events 1 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.	0.00% 0/5 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Hypercalcaemia	14.3% 1/7 • Number of events 1 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.	0.00% 0/5 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Hypokalaemia	14.3% 1/7 • Number of events 1 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.	0.00% 0/5 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.
Renal and urinary disorders Acute Kidney Injury	14.3% 1/7 • Number of events 1 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.	0.00% 0/5 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.
Vascular disorders Hypertension	28.6% 2/7 • Number of events 6 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.	0.00% 0/5 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.
Injury, poisoning and procedural complications Spinal Compression Fracture	0.00% 0/7 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.	20.0% 1/5 • Number of events 1 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour Necrosis	0.00% 0/7 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.	20.0% 1/5 • Number of events 1 • Adverse events (and serious adverse events) were recorded from the first study drug administration up to 28 days after the last study drug dose. Adverse event information was collected by regular investigator assessment and regular laboratory testing.

Other adverse events

Additional Information

Associate Medical Director

Transgene

Phone: + 33 (0)3 88 27 91 00

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Pexa-Vec Combined With Nivolumab - Phase I n=7 Participants 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 Combined With Nivolumab - Phase IIa n=5 Participants 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).	Total n=12 Participants Total of all reporting groups
Age, Continuous	67.7 years STANDARD_DEVIATION 8.1 • n=5 Participants	62.8 years STANDARD_DEVIATION 18.0 • n=7 Participants	65.7 years STANDARD_DEVIATION 12.6 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Stage of HCC per BCLC (Barcelona Clinic Liver Cancer) Stage 0	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Stage of HCC per BCLC (Barcelona Clinic Liver Cancer) Stage A	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Stage of HCC per BCLC (Barcelona Clinic Liver Cancer) Stage B	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Stage of HCC per BCLC (Barcelona Clinic Liver Cancer) Stage C	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Stage of HCC per BCLC (Barcelona Clinic Liver Cancer) Stage D	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
ECOG (Eastern Cooperative Oncology Group) performance status 0	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
ECOG (Eastern Cooperative Oncology Group) performance status 1	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
ECOG (Eastern Cooperative Oncology Group) performance status 2	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
ECOG (Eastern Cooperative Oncology Group) performance status 3	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
ECOG (Eastern Cooperative Oncology Group) performance status 4	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants