A Trial of SHR-1210 (an Anti-PD-1 Inhibitor) in Combination With Apatinib in Patients With Advanced HCC(RESCUE)
Primary Purpose
Hepatocellular Carcinoma
Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
SHR 1210+apatinib
Sponsored by

About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Aged 18 years old, both genders.
- Conform to the clinical diagnosis standard strictly or histological or cytological confirmation of HCC(hepatocellular carcinoma) and with at least one measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to RECIST 1.1.
- Liver function status Child-Pugh Class A.
- Barcelona Clinic Liver Cancer stage Category B or C.
- Failure or intolerance to prior treatment with targeted therapy.
- Eastern Cooperative Oncology Group Performance Status of 0 or 1.
- Life expectancy of at least 12 weeks.
- Adequate bone marrow, liver and renal function (without blood transfusion, without growth factor or blood components support within 14 days before enrollment).
Exclusion Criteria:
- Patients with any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Asthma that requires intermittent use of bronchodilators or other medical intervention should also be excluded.
- Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses > 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration.
- More than one regimen.
- Known history of hypersensitivity to any components of the SHR-1210 formulation, or other antibody formulation.
- Known or occurrence of central nervous system (CNS) metastases or hepatic encephalopathy.
- Patients with tumor burden ≥50% of the liver volume or received liver transplantation.
- Patients with clinical symptoms of ascites.
- Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents(within 3 months): systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg.
- Clinically significant cardiovascular and cerebrovascular diseases, including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, or coronary artery bypass surgery, Congestive heart failure (New York heart association (NYHA) class > 2), ventricular arrhythmia which need medical intervention.
- Coagulation abnormalities (INR>2.0、PT>16s), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
- Previous digestive tract bleeding history within 3 months or evident gastrointestinal bleeding tendency, such as: esophageal varices, local active ulcerative lesions, gastric ulcer and duodenal ulcer, the ulcerous colitis, gastrointestinal diseases such as portal hypertension or resection of tumor with bleeding risk, etc.
- Previous Arterial/venous thrombosis events within 3 months.
- Proteinuria ≥ (++) and 24 hours total urine protein > 1.0 g.
- Prior systemic chemotherapy, radiotherapy, immunotherapy, hormone therapy, surgery or target therapy within 4 weeks (Or 5 half-life of the drug, calculate the longer ) before the study drug administration, or any unresolved AEs > Common Terminology Criteria for Adverse Events (CTCAE) Grade 1.
- Active infection or an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing.
- History of immunodeficiency or human immunodeficiency virus (HIV) infection.
- HBV DNA>2000 IU/ml(or 104copies/ml),HCV RNA>103copies/ml,HBsAg+ and anti-HCV+;
- Patients with other malignant tumor (except cured skin basal cell carcinoma and cervical carcinoma).
- Patients who has bone metastasis, has received Palliative radiotherapy (radiotherapy area > 5% marrow area).
- Patients must not have had prior treatment with SHR-1210 or any other PD-L1 or PD-1 antagonists or apatinib.
- Patients who may receive live vaccine during the study, or previous had vaccination within 4 weeks.
- Any other medical, psychiatric, or social condition deemed by the investigator to be likely to interfere with a subject's rights, safety, welfare, or ability to sign informed consent, cooperate, and participate in the study or would interfere with the interpretation of the results.
Sites / Locations
- The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
SHR-1210+Apatinib
Arm Description
Patients will received apatinib orally every day and SHR-1210 200mg (3mg/kg for underweight patients) iv every 2 weeks.
Outcomes
Primary Outcome Measures
Objective Response Rate (ORR)
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
Secondary Outcome Measures
Duration of Response (DoR)
Duration of Response (DoR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
Disease Control Rate (DCR)
Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
Time to objective response(TTR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
Time to objective response,TTR
9-month survival rate
9-month survival rate
12-month survival rate
12-month survival rate
Overall survival(OS)
Overall survival(OS)
Progression-free survival(PFS)
Progression-free survival(PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
Full Information
NCT ID
NCT03463876
First Posted
March 7, 2018
Last Updated
March 17, 2023
Sponsor
Jiangsu HengRui Medicine Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT03463876
Brief Title
A Trial of SHR-1210 (an Anti-PD-1 Inhibitor) in Combination With Apatinib in Patients With Advanced HCC(RESCUE)
Official Title
A Phase II, Single-arm, Open-labeled Trial of SHR-1210 (an Anti-PD-1 Inhibitor) in Combination With Apatinib in Patients With Advanced HCC
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
February 5, 2018 (Actual)
Primary Completion Date
March 10, 2021 (Actual)
Study Completion Date
March 10, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jiangsu HengRui Medicine Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The purpose of this study is to observe and preliminary explore the efficacy and safety of combination of Apatinib and SHR-1210 regimen in treating advanced hepatocellular carcinoma.
Detailed Description
SHR-1210 is a humanized monoclonal antibody against Programmed death 1(PD-1). Apatinib is a new kind of selective Vascular Endothelial Growth Factor Receptor 2(VEGFR-2) tyrosine kinase inhibitor (TKI).
Patients with advanced HCC who failed or intolerable to sorafenib will received apatinib 250mg orally every day and SHR-1210 200mg (3mg/kg for underweight patients) iv every 2 weeks. The efficacy and safety will be observed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
190 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SHR-1210+Apatinib
Arm Type
Experimental
Arm Description
Patients will received apatinib orally every day and SHR-1210 200mg (3mg/kg for underweight patients) iv every 2 weeks.
Intervention Type
Drug
Intervention Name(s)
SHR 1210+apatinib
Intervention Description
SHR-1210 200mg (3mg/kg for underweight patients) iv every 2 weeks;Apatinib,250 mg/day.
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
Time Frame
Up to approximately 12 months
Secondary Outcome Measure Information:
Title
Duration of Response (DoR)
Description
Duration of Response (DoR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
Time Frame
Up to approximately 12 months
Title
Disease Control Rate (DCR)
Description
Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
Time Frame
Up to approximately 12 months
Title
Time to objective response(TTR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
Description
Time to objective response,TTR
Time Frame
Up to approximately 12 months
Title
9-month survival rate
Description
9-month survival rate
Time Frame
Up to approximately 12 months
Title
12-month survival rate
Description
12-month survival rate
Time Frame
Up to approximately 12 months
Title
Overall survival(OS)
Description
Overall survival(OS)
Time Frame
Up to approximately 18 months
Title
Progression-free survival(PFS)
Description
Progression-free survival(PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
Time Frame
Up to approximately 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Aged 18 years old, both genders.
Conform to the clinical diagnosis standard strictly or histological or cytological confirmation of HCC(hepatocellular carcinoma) and with at least one measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to RECIST 1.1.
Liver function status Child-Pugh Class A.
Barcelona Clinic Liver Cancer stage Category B or C.
Failure or intolerance to prior treatment with targeted therapy.
Eastern Cooperative Oncology Group Performance Status of 0 or 1.
Life expectancy of at least 12 weeks.
Adequate bone marrow, liver and renal function (without blood transfusion, without growth factor or blood components support within 14 days before enrollment).
Exclusion Criteria:
Patients with any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Asthma that requires intermittent use of bronchodilators or other medical intervention should also be excluded.
Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses > 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration.
More than one regimen.
Known history of hypersensitivity to any components of the SHR-1210 formulation, or other antibody formulation.
Known or occurrence of central nervous system (CNS) metastases or hepatic encephalopathy.
Patients with tumor burden ≥50% of the liver volume or received liver transplantation.
Patients with clinical symptoms of ascites.
Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents(within 3 months): systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg.
Clinically significant cardiovascular and cerebrovascular diseases, including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, or coronary artery bypass surgery, Congestive heart failure (New York heart association (NYHA) class > 2), ventricular arrhythmia which need medical intervention.
Coagulation abnormalities (INR>2.0、PT>16s), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
Previous digestive tract bleeding history within 3 months or evident gastrointestinal bleeding tendency, such as: esophageal varices, local active ulcerative lesions, gastric ulcer and duodenal ulcer, the ulcerous colitis, gastrointestinal diseases such as portal hypertension or resection of tumor with bleeding risk, etc.
Previous Arterial/venous thrombosis events within 3 months.
Proteinuria ≥ (++) and 24 hours total urine protein > 1.0 g.
Prior systemic chemotherapy, radiotherapy, immunotherapy, hormone therapy, surgery or target therapy within 4 weeks (Or 5 half-life of the drug, calculate the longer ) before the study drug administration, or any unresolved AEs > Common Terminology Criteria for Adverse Events (CTCAE) Grade 1.
Active infection or an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing.
History of immunodeficiency or human immunodeficiency virus (HIV) infection.
HBV DNA>2000 IU/ml(or 104copies/ml),HCV RNA>103copies/ml,HBsAg+ and anti-HCV+;
Patients with other malignant tumor (except cured skin basal cell carcinoma and cervical carcinoma).
Patients who has bone metastasis, has received Palliative radiotherapy (radiotherapy area > 5% marrow area).
Patients must not have had prior treatment with SHR-1210 or any other PD-L1 or PD-1 antagonists or apatinib.
Patients who may receive live vaccine during the study, or previous had vaccination within 4 weeks.
Any other medical, psychiatric, or social condition deemed by the investigator to be likely to interfere with a subject's rights, safety, welfare, or ability to sign informed consent, cooperate, and participate in the study or would interfere with the interpretation of the results.
Facility Information:
Facility Name
The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100071
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
33087333
Citation
Xu J, Shen J, Gu S, Zhang Y, Wu L, Wu J, Shao G, Zhang Y, Xu L, Yin T, Liu J, Ren Z, Xiong J, Mao X, Zhang L, Yang J, Li L, Chen X, Wang Z, Gu K, Chen X, Pan Z, Ma K, Zhou X, Yu Z, Li E, Yin G, Zhang X, Wang S, Wang Q. Camrelizumab in Combination with Apatinib in Patients with Advanced Hepatocellular Carcinoma (RESCUE): A Nonrandomized, Open-label, Phase II Trial. Clin Cancer Res. 2021 Feb 15;27(4):1003-1011. doi: 10.1158/1078-0432.CCR-20-2571. Epub 2020 Oct 21.
Results Reference
derived
Learn more about this trial
A Trial of SHR-1210 (an Anti-PD-1 Inhibitor) in Combination With Apatinib in Patients With Advanced HCC(RESCUE)
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