Hepatocellular Carcinoma
Conditions
Keywords
cadonilimab (anti PD-1/CTLA-4 bispecific antibody)
Brief summary
To evaluate the efficacy and safety of cadonilimab combined with Regorafenib in patients with hepatocellular carcinoma who failed camrelizumab plus apatinib.
Interventions
cadonilimab: 6mg/kg iv D1 Q2W; regorafenib: 80mg QD oral; Eligible patients will receive cadonilimab combined with regorafenib, until disease progression or intolerable toxicity or death or withdrawal of informed consent, whichever occurred first
Sponsors
Meng Chao Hepatobiliary Hospital of Fujian Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Sign a written informed consent form before enrollment; 2. Age \>18 years old, both sex; 3. Histological or pathological confirmed intermediate or advanced hepatocellular carcinoma, or patients with cirrhosis who meet the clinical diagnostic criteria for hepatocellular carcinoma of the American Association for the Study of Liver Diseases (AASLD); 4. Have progressed on the combination treatment of camrelizumab and apatinib for HCC 5. Child-Pugh Class A; 6. ECOG PS score: 0\ 1; 7. At least 1 measurable lesion (RECIST1.1) 8. Expected survival period≥12 weeks 9. The function of vital organs meets the following requirements (excluding the use of any blood components and cell growth factors within 14 days): 1\. Blood routine: Neutrophils≥1.5×109/L Platelet count ≥75×109/L Hemoglobin ≥ 90g/L; 2. Liver and kidney function: Serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance ≥ 50 ml/min (Cockcroft-Gault formula); Total bilirubin (TBIL) ≤ 3 times the upper limit of normal (ULN); Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≤ 10 times the upper limit of normal (ULN); urine protein \< 2+; if urine protein ≥ 2+, 24-hour urine protein quantification shows that the protein must be ≤ 1g; 10. Normal coagulation function, no active bleeding or thrombosis disease 1. International normalized ratio INR≤1.5×ULN; 2. Partial thromboplastin time APTT≤1.5×ULN; 3. Prothrombin time PT≤1.5×ULN; 11. Non-surgical sterilization or female patients of childbearing age 12. Subjects voluntarily join this study, have good compliance, and cooperate with safety and survival follow-up Main
Exclusion criteria
1. Containing components such as fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and cholangiocarcinoma that have been previously confirmed by histology/cytology; 2. Have a history of hepatic encephalopathy; 3. Have a history of liver transplantation; 4. There is clinically significant pericardial effusion, and there are clinical symptoms of pleural effusion that require drainage; 5. Clinically apparent ascites is defined as meeting the following criteria: ascites can be detected by physical examination during screening or ascites needs to be drained during screening; 6. Simultaneous infection with HBV and HCV (having a history of HCV infection but negative HCV RNA can be considered as not being infected with HCV); 7. Presence of central nervous system metastasis or meningeal metastasis 8. Bleeding from esophageal or gastric varices caused by portal hypertension has occurred within 6 months before the first dose 9. Patients with any bleeding or bleeding event ≥CTCAE grade 3 within 4 weeks before the first dose 10. Arterial and venous thromboembolic events occurred within 6 months before the first dose 11. Uncontrolled high blood pressure 12. Symptomatic congestive heart failure 13. Severe bleeding tendency or coagulation disorder 14. Have a history of gastrointestinal perforation and/or fistula, intestinal obstruction within 6 months before the first dose 15. Active autoimmune disease or a history of autoimmune disease 16. Patients with HIV 17. According to the investigator's judgment, patients with other serious concomitant diseases that endanger the patient's safety or affect the patient's completion of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| objective response rate (ORR) per RECIST1.1 | Up to two years | The proportion of all subjects with the best overall response (BOR) as complete remission (CR) or partial remission (PR) according to RECIST 1.1 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival（PFS） | Up to two years | PFS was defined as the time from the first dose to the time of the first documented tumor progression (assessed by RECIST1.1 criteria) or the time of death from any cause, whichever occurred first. |
| Overall survival（OS） | Up to three years | Defined as the time from the first dose to the death from any cause. |
| Duration of response (DOR) | Up to two years | Defined as the time from the first dose to disease progression or death in patients who achieve complete or partial response |
| Occurence of AE and SAE | Up to two years | Occurence of Adverse Event (AE) and Serious Adverse Event (SAE) （NCI CTCAE 5.0） |
Countries
China
Outcome results
None listed