Hepatocellular Carcinoma Non-Resectable
Conditions
Brief summary
This a randomized controlled Phase 2/3 study to evaluate the efficacy and safety of SHR-1210 in subjects with advanced HCC who failed or intolerable to prior systemic treatment. The primary study hypothesis is that SHR-1210 treatment improves Objective Response Rate and Overall Survival when compare with SOC.
Detailed description
In June 2017, this study was revised to expand the Phase 2 part to enroll more subjects and remove the Phase 3 part under the same protocol. A Phase 3 study will be initiated separately.
Interventions
BIOLOGICALSHR-1210
SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
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
1. Histologically confirmed HCC in advanced stage; not suitable to surgery or local regional treatment; with at least one measurable lesion per RECIST 1.1 2. Failed or intolerable to at least one prior systemic treatment for advanced HCC 3. ECOG Performance Status of 0 or1 4. Child-Pugh Class A or B with 7 points 5. Life Expectancy of at least 12 weeks 6. HBV DNA\<500 IU/ml 7. Adequate organ function 8. Male or female participants of childbearing potential must be willing to use an adequate method of contraception starting with the first dose of study drug through 60 days for female subjects and 120 days for male subjects after the last dose of study drug
Exclusion criteria
1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC 2. Known liver transplant or plan to transplant 3. GI hemorrhage with 6 months 4. History or current brain metastases 5. Active known, or suspected autoimmune disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | approximate 3 years | Tumour responses were evaluated by the independent review committee (IRC) according to RECIST 1.1.The primary endpoints were the proportion of patients with a IRC-assessed objective response (defined as the percentage of patients whose best overall response was confirmed complete or partial response). |
| 6-month Overall Survival Rate | from the date of the first dose to 6 months | 6-month overall survival rate (defined as cumulative overall survival rate from the date of the first dose to 6 months) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | approximate 3 years | Time from first dose to death from any cause |
| Adverse Events | approximate 3 years | Number of Subjects with one or more adverse events as assessed by CTCAE 4.03 |
| Duration of Response | approximate 3 years | time from first response to progression or death base on the IRC assessment |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SHR-1210 Q2W Subjects receive SHR-1210 intravenous at the dose 3mg/kg on Day 1 every 2 weeks
SHR-1210: SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody | 109 |
| SHR-1210 Q3W Subjects receive SHR-1210 intravenous at the dose 3mg/kg on Day 1 every 3 weeks
SHR-1210: SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody | 108 |
| Total | 217 |
Baseline characteristics
| Characteristic | SHR-1210 Q3W | Total | SHR-1210 Q2W |
|---|---|---|---|
| Age, Continuous | 49.5 years | 49.0 years | 48.0 years |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment China | 108 participants | 217 participants | 109 participants |
| Sex: Female, Male Female | 10 Participants | 21 Participants | 11 Participants |
| Sex: Female, Male Male | 98 Participants | 196 Participants | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 27 / 109 | 29 / 108 |
| other Total, other adverse events | 108 / 109 | 107 / 108 |
| serious Total, serious adverse events | 50 / 109 | 46 / 108 |
Outcome results
Primary
6-month Overall Survival Rate
6-month overall survival rate (defined as cumulative overall survival rate from the date of the first dose to 6 months)
Time frame: from the date of the first dose to 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SHR-1210 Q2W | 6-month Overall Survival Rate | 75.9 percentage of participants |
| SHR-1210 Q3W | 6-month Overall Survival Rate | 73.0 percentage of participants |
Primary
Objective Response Rate
Tumour responses were evaluated by the independent review committee (IRC) according to RECIST 1.1.The primary endpoints were the proportion of patients with a IRC-assessed objective response (defined as the percentage of patients whose best overall response was confirmed complete or partial response).
Time frame: approximate 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SHR-1210 Q2W | Objective Response Rate | 11.9 percentage of participants |
| SHR-1210 Q3W | Objective Response Rate | 16.7 percentage of participants |
Secondary
Adverse Events
Number of Subjects with one or more adverse events as assessed by CTCAE 4.03
Time frame: approximate 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SHR-1210 Q2W | Adverse Events | 109 participants |
| SHR-1210 Q3W | Adverse Events | 108 participants |
Secondary
Duration of Response
time from first response to progression or death base on the IRC assessment
Time frame: approximate 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SHR-1210 Q2W | Duration of Response | 30.4 months |
| SHR-1210 Q3W | Duration of Response | 30.5 months |
Secondary
Overall Survival
Time from first dose to death from any cause
Time frame: approximate 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SHR-1210 Q2W | Overall Survival | 14.3 months |
| SHR-1210 Q3W | Overall Survival | 13.2 months |