A Clinical Study to Observe the Effectiveness and Safety of IBI310, Bevacizumab Combined With Sintilimab in the Treatment of Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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This is a randomized, open-label, multicenter Phase Ib study to evaluate the effectiveness and safety of different doses of IBI310, bevacizumab combined with sintilimab in patients with locally advanced or metastatic HCC who have not previously received systemic therapy, are unsuitable for radical surgical resection or local treatment, or have progressive disease after surgical resection or local treatment.

Official Title
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A Randomized, Open-label, Multicenter Phase Ib Clinical Study to Observe the Effectiveness and Safety of Different Doses of IBI310,Bevacizumab Combined With Sintilimab in the First-line Treatment of Advanced Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: IBI310（0.5mg/kg）
* Drug: IBI310（0.3mg/kg）
* Drug: sintilimab
* Drug: bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically/cytologically confirmed hepatocellular carcinoma, or meeting the clinical diagnostic criteria for hepatocellular carcinoma ; Aged ≥18 years,≤75 years; ECOG performance status score of 0 or 1 point; Barcelona Clinic Liver Cancer (BCLC) stage C, or Stage B not suitable for radical surgery and/or local treatment; No systemic antitumor treatment for hepatocellular carcinoma before the first administration; At least 1 measurable lesion according to the Response Evaluation Criteria in Solid Tumors Version 1.1(RECIST V1.1), or measurable lesion with definite progression after local treatment (based on RECIST V1.1 criteria); Child-Pugh Class A or B(≤7); Adequate organ and bone marrow function. Expected life time is over 12 weeks. Take effective contraceptive measures Willing to attend the study and having given the ICF Exclusion Criteria: Known fibrolamellar HCC, sarcomatoid HCC, mixed cholangiocarcinoma and HCC History of hepatic encephalopathy or liver transplantation Pleural, ascites, and pericardial effusion with clinical symptoms requiring drainage HBV-DNA>2000 IU/ML or 10^4 copies/ml；Untreated positive HCV-RNA；HbsAg and anti-HCV antibody were both positive History of GI bleeding within 6 months, or severe (G3) varices at endoscopy within 3 months Arteriovenous embolism within 6 months The tumor thrombus involved both main and branch portal veins, main portal veins and mesenteric veins or inferior vena cava. Antiplatelet drugs were administered for 10 days for therapeutic purposes 2 weeks before administration Uncontrolled hypertension Unrecovered AE（>CTCAE grade 1） due to previous treatment Heart failure (NYHA Classification III-IV), or poorly controlled arrhythmias History of gastrointestinal perforation, fistula, intestinal obstruction, extensive bowel resection, Crohn's disease, ulcerative colitis, or chronic diarrhea With lung fibrosis, interstitial lung disease, pneumoconiosis, drug-associated pneumonia and serious impairment in lung function Active tuberculosis Infected with HIV or syphilis Severe infections that are active or clinically poorly controlled Use of immunosuppressive drugs within 4 weeks prior to initial dosing Receipt of live attenuated vaccine within 4 weeks prior to randomization Significant traumatic injury or major surgical procedure within 28 days prior to randomization Other conditions that the investigator judged inappropriate for inclusion Prior immunotherapy or targeted therapy Treatment of Traditional Chinese medicine with anti-tumor indications or drugs with immunomodulatory effects whitin 2 weeks Pregnant or breast-feeding women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A（IBI310 0.5mg/kg）<br>IBI310 0.5mg/kg IV d1 Q6W, sintilimab 200mg IV d1 Q3W, combined with bevacizumab 15mg/kg IV d1，Q3W | Drug: IBI310（0.5mg/kg）<br>* IBI310 0.5mg/kg IV d1 Q6W<br>Drug: sintilimab<br>* sintilimab 200 mg IV d1 Q3W<br>Drug: bevacizumab<br>* bevacizumab 15 mg/kg IV d1，Q3W<br>|
| Experimental: Arm B（IBI310 0.3mg/kg）<br>IBI310 0.3mg/kg IV d1 Q6W, sintilimab 200mg IV d1 Q3W, combined with bevacizumab 15mg/kg IV d1，Q3W | Drug: IBI310（0.3mg/kg）<br>* IBI310 0.3mg/kg IV d1 Q6W<br>Drug: sintilimab<br>* sintilimab 200 mg IV d1 Q3W<br>Drug: bevacizumab<br>* bevacizumab 15 mg/kg IV d1，Q3W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | efficacy | The proportion of patients with complete response or partial response, through study completion, an average of 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response（DOR）according to RECIST V1.1 criteria | efficacy | From date of randomization until the date of first documented progression, up to 48 months | 
| Duration of Response（DOR）according to mRECIST criteria | efficacy | From date of randomization until the date of first documented progression, up to 48 months | 
| Disease Control Rate（DCR） according to RECIST V1.1 criteria | efficacy | The percentage of patients whose therapeutic intervention has led to a complete response, partial response, or stable disease, through study completion, an average of 3 years | 
| Disease Control Rate（DCR） according to mRECIST criteria | efficacy | The percentage of patients whose therapeutic intervention has led to a complete response, partial response, or stable disease, through study completion, an average of 3 years | 
| Time to Progression（TTP）according to RECIST V1.1 criteria | efficacy | From date of randomization until the date of first documented progression, up to 48 months | 
| Time to Progression（TTP）according to mRECIST criteria | efficacy | From date of randomization until the date of first documented progression, up to 48 months | 
| Progresison Free Surviva（PFS）according to RECIST V1.1 criteria | efficacy | From date of randomization until the date of the first documented progression or date of death from any cause, whichever comes first, up to 48 months | 
| Progresison Free Surviva（PFS）according to mRECIST criteria | efficacy | From date of randomization until the date of the first documented progression or date of death from any cause, whichever comes first, up to 48 months | 
| Overall survival (OS) | efficacy | From date of randomization until death from any cause，through study completion, an average of 3 years | 
| Immune Best Overall Response（iBOR）according to iRECIST criteria | efficacy | The best timepoint response recorded from the start of the study treatment until the end of treatment, taking into account any requirement for confirmation, through study completion, an average of 3 years |