Hepatocellular Carcinoma, Intermediate Stage of Hepatocellular Carcinoma
Conditions
Keywords
HCC, Durvalumab, Tremelimumab, Immunotherapy, PD-L1, Antibodies, Hepatocellular Carcinoma, CTLA-4, DEB-TACE
Brief summary
The purpose of this study is to determine the safety and efficacy of immunotherapy durvalumab and tremelimumab combined with DEB-TACE in patients with Hepatocellular Carcinoma.
Interventions
DRUGTremelimumab
Tremelimumab 300 mg IV in combination with Durvalumab 1500mg about 2 weeks after their first DEB-TACE.
DRUGDurvalumab
Durvalumab 1500mg IV every 4 weeks for up to a maximum of 13 cycles (about 12 months) or until confirmed disease progression.
Sponsors
AstraZeneca
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent form * Age ≥18 years. * Patients with diagnosis of HCC either by high-resolution imaging (triple-phase CT or MRI) and/or by tumor biopsy. * Patient is not on systemic treatment for diagnosis of HCC * HCC meeting Barcelona Clinic Liver Cancer (BCLC) stage B (intermediate stage), with measurable lesions on CT or MRI and without extrahepatic spread * Have measurable disease * Have disease that responds to DEB-TACE * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Child-Pugh Score of A or early B (score ≤8) without clinically significant ascites * Body weight \>30 kg * Patients must have adequate organ function defined by study-specified laboratory tests. * Evidence of post-menopausal status or negative pregnancy test * Willing and able to comply with study procedures * Willing to undergo a liver biopsy
Exclusion criteria
* Anyone involved with the planning and/or conduct of the study. * Has participated in another investigational study during the last 6 months. * Any concurrent anticancer therapy or received therapy ≤30 days prior to study. * Major surgical procedure at the time of study enrollment or within 28 days prior to the first dose of study drug. * Have a vascular invasion or extrahepatic tumor. * Main portal vein thrombosis present on imaging. * Uncontrolled hepatic encephalopathy at time of enrollment. - Ascites within 6 weeks prior to study treatment. * Any contraindications for embolization. * Has an active infection such as Tuberculosis, HIV, hepatitis B or C. * History of another primary malignancy or myeloproliferative disorder. * History of leptomeningeal carcinomatosis. * History of active primary immunodeficiency. * Any unresolved toxicities from previous anticancer therapy. * Active or prior documented GI bleeding due to ulcer or esophageal varices bleeding within 6 months. * History or current use of immunosuppressive medications within 14 days prior to study medications. * Major surgical procedure within 28 days prior to the first dose of IP. * Has an active known or suspected autoimmune disease. * Patients with hypothyroidism. * Any active skin conditions. * History of allogenic organ transplantation. * Significant heart disease. * Patients weighing \< 30 kg. * Patients with celiac disease not controlled by diet alone. * Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Have received a live vaccine within 30 days prior to study drug. * Woman who are pregnant or breastfeeding. * Known allergy or hypersensitivity to the study drug. * Have received durvalumab, tremelimumab, anti-PD-1, anti-PD-L1 or anti-CTLA-4 in a prior study. * Unwilling or unable to follow the study schedule for any reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | up to 26 months | Objective Response Rate (ORR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on mRECIST criteria. CR = Disappearance of any intratumoral arterial enhancement in all target lesions, PR = At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Drug-related Toxicity | up to 16 months | Number of participants experiencing drug-related adverse events (AE) Grade 3 or higher as defined by CTCAE v5.0 |
| Progression Free Survival (PFS) | up to 58 months | Progression free survival is defined as the time from start of the treatment until the documentation of disease progression according to mRECIST or death due to any cause, whichever occurs first. Estimation based on the Kaplan-Meier curve. |
| Overall Survival (OS) | up to 58 months | Overall survival is the time from the start of first dose of study drug to death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Durvalumab in Combination With Tremelimumab Drug: Durvalumab 1500mg IV + Tremelimumab 300 mg IV , single infusion about 2 weeks after first DEB-TACE procedure.
Drug: Durvalumab (monotherapy) 1500 mg IV infusion every 4 weeks, for maximum 13 cycles or until confirmed disease progression. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | 1 subject was removed from the study due to non compliance and was never treated. | 1 |
Baseline characteristics
| Characteristic | Durvalumab in Combination With Tremelimumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 14 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Hepatitis B or C | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 20 |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 10 / 20 |
Outcome results
Primary
Objective Response Rate (ORR)
Objective Response Rate (ORR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on mRECIST criteria. CR = Disappearance of any intratumoral arterial enhancement in all target lesions, PR = At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions.
Time frame: up to 26 months
Population: Participants who received at least one dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Durvalumab in Combination With Tremelimumab | Objective Response Rate (ORR) | 11 Participants |
Secondary
Drug-related Toxicity
Number of participants experiencing drug-related adverse events (AE) Grade 3 or higher as defined by CTCAE v5.0
Time frame: up to 16 months
Population: Participants who received at least one dose of study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Durvalumab in Combination With Tremelimumab | Drug-related Toxicity | Any gr 3 or higher AE | 4 Participants |
| Durvalumab in Combination With Tremelimumab | Drug-related Toxicity | Hepatitis | 1 Participants |
| Durvalumab in Combination With Tremelimumab | Drug-related Toxicity | Diarrhea | 1 Participants |
| Durvalumab in Combination With Tremelimumab | Drug-related Toxicity | Myalgia | 1 Participants |
| Durvalumab in Combination With Tremelimumab | Drug-related Toxicity | Myocarditis | 1 Participants |
| Durvalumab in Combination With Tremelimumab | Drug-related Toxicity | Myositis | 1 Participants |
| Durvalumab in Combination With Tremelimumab | Drug-related Toxicity | Nausea | 1 Participants |
| Durvalumab in Combination With Tremelimumab | Drug-related Toxicity | Pericarditis | 1 Participants |
| Durvalumab in Combination With Tremelimumab | Drug-related Toxicity | Pruritus | 1 Participants |
| Durvalumab in Combination With Tremelimumab | Drug-related Toxicity | Rash maculo-papular | 2 Participants |
Secondary
Overall Survival (OS)
Overall survival is the time from the start of first dose of study drug to death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.
Time frame: up to 58 months
Population: Participants who received at least one dose of study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab in Combination With Tremelimumab | Overall Survival (OS) | 28.8 months |
Secondary
Progression Free Survival (PFS)
Progression free survival is defined as the time from start of the treatment until the documentation of disease progression according to mRECIST or death due to any cause, whichever occurs first. Estimation based on the Kaplan-Meier curve.
Time frame: up to 58 months
Population: Participants who received at least one dose of study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab in Combination With Tremelimumab | Progression Free Survival (PFS) | 6.1 months |