This study is to evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with sintilimab and bevacizumab in patients with unresectable intermediate or advanced hepatocellular carcinoma (HCC).
This is a Phase Ib study to evaluate the safety and efficacy of TACE combined with sintilimab and bevacizumab in patients with unresectable intermediate or advanced HCC. 36-39 subjects with unresectable intermediate or advanced HCC will be enrolled in the study. This study includes dose escalation and dose expansion stage. 6-9 subjects will be enrolled in dose escalation stage for the safety evaluation. Then, sintilimab 200mg/kg IV. every three weeks (q3w) + the select specific dose of bevacizumab 7.5mg/kg (group 1) or 15mg/kg (group2) IV q3w, expand to 36 patients (18 patients each group) for the further safety and efficacy study. Sintilimab and bevacizumab will be started at 3-7 days after the first TACE. TACE will be repeated if clinically indicated based on the evaluation of follow-up laboratory and imaging examination. And the study treatment of sintilimab and bevacizumab will last up to 24 months, or until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Sintilimab and bevacizumab are administered at 3-7 days after the first TACE. The study includes dose escalation and dose expansion stage. 6-9 subjects will be enrolled in dose escalation stage for the safety and efficacy evaluation. Then, Sintilimab 200mg/kg IV. q3w+ select specific dose of bevacizumab (7.5mg/kg or 15 mg/kg IV. q3w), expand to 36-39 patients for the further safety and efficacy study. The study treatment of sintilimab and bevacizumab lasts up to 24 months. TACE can be repeated when indicated clinically.
The Second Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, China
Adverse Events (AEs)
Number of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), AE of special interest (AESI), serious adverse event (SAE), assessed by NCI CTCAE v5.0.
Time frame: 24 months
Progression free survival (PFS) assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune-related RECIST (irRECIST).
The time from initiation of treatment until the first occurrence of disease progression or death from any cause, whichever occurs first.
Time frame: 24 months
Overall survival (OS)
The time from initiation of treatment until the date of death from any cause.
Time frame: 24 months
Objective response rate (ORR) assessed by investigators according to RECIST 1.1 and irRECIST.
The percentage of patients who had a best overall tumor response rating of complete response (CR) or partial response (PR).
Time frame: 24 months
Disease control rate (DCR) assessed by investigators according to RECIST 1.1 and irRECIST.
The percentage of patients who had a tumor response rating of CR, PR, or stable disease (SD).
Time frame: 24 months
Duration of response (DOR) assessed by investigators according to RECIST 1.1 and irRECIST.
The time from the first occurrence of a documented objective response to disease progression (PD) or death.
Time frame: 24 months
PFS assessed by investigators according to Modified RECIST (mRECIST).
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The time from initiation of treatment until the first occurrence of disease progression or death from any cause, whichever occurs first.
Time frame: 24 months
ORR assessed by investigators according to mRECIST.
The percentage of patients who had a best overall tumor response rating of CR or PR.
Time frame: 24 months
DCR assessed by investigators according to mRECIST.
The percentage of patients who had a tumor response rating of CR, PR, or SD.
Time frame: 24 months
DOR assessed by investigators according to mRECIST.
The time from the first occurrence of a documented objective response to PD or death.
Time frame: 24 months