Hepatocellular Carcinoma (HCC)
Conditions
Keywords
Hepatocellular Carcinoma (HCC), Pexastimogene Devacirepvec (Pexa-Vec), Sorafenib, GM-CSF therapy, Thymidine Kinase-Deactivated Vaccinia Virus, Oncology, Recombinant Vaccinia Virus, Oncolytic Virus Therapy, Oncolytic virotherapy
Brief summary
This is a randomized Phase 3 study to determine whether treatment with vaccinia virus based immunotherapy (Pexa-Vec) followed by sorafenib increases survival compared to treatment with sorafenib in patients with advanced hepatocellular carcinoma who have not received prior systemic therapy.
Detailed description
This is a multi-center, randomized, open-label, Phase 3 study comparing Pexa Vec followed by sorafenib versus sorafenib in patients with advanced HCC without prior systemic therapy. A total of 459 patients were randomly assigned to 2 treatment arms- 234 patients in the Pexa-Vec followed by sorafenib treatment group and 225 patients in the sorafenib only treatment group.
Interventions
BIOLOGICALPexastimogene Devacirepvec (Pexa Vec)
Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells.
DRUGSorafenib
Sorafenib belongs to the pharmacotherapeutic group of antineoplastic agents, protein kinase inhibitors, ATC code: L01XE05. Sorafenib is a multi-kinase inhibitor which has demonstrated both anti-proliferative and anti-angiogenic properties in vitro and in vivo. Sorafenib is approved for the treatment of advanced HCC and is the Standard Of Care for this disease.
Sponsors
SillaJen, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological/cytological diagnosis of primary HCC * Advanced stage HCC (Barcelona Clinic Liver Cancer \[BCLC\] Stage C or B per American Association for the Study of Liver Disease \[AASLD\] guidelines) * 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 and/or ultrasound) * Child-Pugh Class A * 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 * Bulky disease patients - tumors encompassing \>50% of the liver volume and / or inferior vena cava invasion * Known significant immunodeficiency due to underlying illness (e.g., HIV/AIDS) and/or immune-suppressive medication including high-dose corticosteroids * Ongoing severe inflammatory skin condition (as determined by the Investigator) requiring medical treatment * History of severe eczema (as determined by the Investigator) requiring medical treatment * Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | From date of randomization to the date of first documented radiographic tumor progression up to 53 months | Percentage of participants who showed overall response during their participation in the study. Per Modified Response Evaluation Criteria In Solid Tumors Criteria (mRECIST) and assessed by tri-phasic contrast enhanced CT: Complete Response (CR), Disappearance of intratumoral enhancing area; Partial Response (PR), \>=30% decrease in the sum of the diameters of enhancing area; Overall Response (OR) = CR + PR. |
Countries
Australia, Canada, China, France, Germany, Hong Kong, Israel, Italy, New Zealand, Portugal, Singapore, South Korea, Taiwan, Thailand, United Kingdom, United States
Contacts
STUDY_DIRECTORSillaJen Medical
SillaJen, Inc.
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pexa-Vec Followed by Sorafenib Pexa-Vec (pexastimogene devacirepvec) will be administered as 3 bi-weekly intratumoral (IT) injections of 1e9 pfu at day 1 and weeks 2 and 4, followed by sorafenib at Week 6.
Pexastimogene Devacirepvec (Pexa Vec): Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells.
Sorafenib: Sorafenib belongs to the pharmacotherapeutic group of antineoplastic agents, protein kinase inhibitors, ATC code: L01XE05.
Sorafenib is a multi-kinase inhibitor which has demonstrated both anti-proliferative and anti-angiogenic properties in vitro and in vivo.
Sorafenib is approved for the treatment of advanced HCC and is the Standard Of Care for this disease. | 234 |
| Sorafenib Sorafenib (400 mg twice daily) begins on Day 1.
Sorafenib: Sorafenib belongs to the pharmacotherapeutic group of antineoplastic agents, protein kinase inhibitors, ATC code: L01XE05.
Sorafenib is a multi-kinase inhibitor which has demonstrated both anti-proliferative and anti-angiogenic properties in vitro and in vivo.
Sorafenib is approved for the treatment of advanced HCC and is the Standard Of Care for this disease. | 225 |
| Total | 459 |
Baseline characteristics
| Characteristic | Sorafenib | Total | Pexa-Vec Followed by Sorafenib |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 77 Participants | 178 Participants | 101 Participants |
| Age, Categorical Between 18 and 65 years | 148 Participants | 281 Participants | 133 Participants |
| Age, Continuous | 60.5 years STANDARD_DEVIATION 11.06 | 60.9 years STANDARD_DEVIATION 10.55 | 61.3 years STANDARD_DEVIATION 10.05 |
| ECOG performance status 0 | 142 Participants | 288 Participants | 146 Participants |
| ECOG performance status 1 | 83 Participants | 171 Participants | 88 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 11 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 219 Participants | 448 Participants | 229 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Australia | 5 participants | 14 participants | 9 participants |
| Region of Enrollment Canada | 4 participants | 9 participants | 5 participants |
| Region of Enrollment China | 40 participants | 82 participants | 42 participants |
| Region of Enrollment France | 8 participants | 20 participants | 12 participants |
| Region of Enrollment Germany | 6 participants | 13 participants | 7 participants |
| Region of Enrollment Hong Kong | 3 participants | 4 participants | 1 participants |
| Region of Enrollment Israel | 2 participants | 3 participants | 1 participants |
| Region of Enrollment Italy | 3 participants | 4 participants | 1 participants |
| Region of Enrollment New Zealand | 27 participants | 54 participants | 27 participants |
| Region of Enrollment Portugal | 3 participants | 5 participants | 2 participants |
| Region of Enrollment Singapore | 3 participants | 11 participants | 8 participants |
| Region of Enrollment South Korea | 68 participants | 129 participants | 61 participants |
| Region of Enrollment Taiwan | 10 participants | 23 participants | 13 participants |
| Region of Enrollment Thailand | 5 participants | 7 participants | 2 participants |
| Region of Enrollment United Kingdom | 4 participants | 7 participants | 3 participants |
| Region of Enrollment United States | 34 participants | 74 participants | 40 participants |
| Sex: Female, Male Female | 43 Participants | 73 Participants | 30 Participants |
| Sex: Female, Male Male | 182 Participants | 386 Participants | 204 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 33 / 218 | 25 / 217 |
| other Total, other adverse events | 218 / 218 | 214 / 217 |
| serious Total, serious adverse events | 117 / 218 | 77 / 217 |
Outcome results
Primary
Overall Response Rate (ORR)
Percentage of participants who showed overall response during their participation in the study. Per Modified Response Evaluation Criteria In Solid Tumors Criteria (mRECIST) and assessed by tri-phasic contrast enhanced CT: Complete Response (CR), Disappearance of intratumoral enhancing area; Partial Response (PR), \>=30% decrease in the sum of the diameters of enhancing area; Overall Response (OR) = CR + PR.
Time frame: From date of randomization to the date of first documented radiographic tumor progression up to 53 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pexa-Vec Followed by Sorafenib | Overall Response Rate (ORR) | 19.2 percentage of participants |
| Sorafenib | Overall Response Rate (ORR) | 20.9 percentage of participants |