Back to resultsA Clinical Study to Observe the Effectiveness and Safety of IBI310, Bevacizumab Combined With Sintilimab in the Treatment of Advanced Hepatocellular Carcinoma
Primary Purpose
Hepatocellular Carcinoma
Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
IBI310（0.5mg/kg）
IBI310（0.3mg/kg）
sintilimab
bevacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm A（IBI310 0.5mg/kg）
Arm B（IBI310 0.3mg/kg）
Arm Description
IBI310 0.5mg/kg IV d1 Q6W, sintilimab 200mg IV d1 Q3W, combined with bevacizumab 15mg/kg IV d1，Q3W
IBI310 0.3mg/kg IV d1 Q6W, sintilimab 200mg IV d1 Q3W, combined with bevacizumab 15mg/kg IV d1，Q3W
Outcomes
Primary Outcome Measures
Objective response rate (ORR)
efficacy
Secondary Outcome Measures
Duration of Response（DOR）according to RECIST V1.1 criteria
efficacy
Duration of Response（DOR）according to mRECIST criteria
efficacy
Disease Control Rate（DCR） according to RECIST V1.1 criteria
efficacy
Disease Control Rate（DCR） according to mRECIST criteria
efficacy
Time to Progression（TTP）according to RECIST V1.1 criteria
efficacy
Time to Progression（TTP）according to mRECIST criteria
efficacy
Progresison Free Surviva（PFS）according to RECIST V1.1 criteria
efficacy
Progresison Free Surviva（PFS）according to mRECIST criteria
efficacy
Overall survival (OS)
efficacy
Immune Best Overall Response（iBOR）according to iRECIST criteria
efficacy
Full Information
NCT ID
NCT05363722
First Posted
April 14, 2022
Last Updated
May 5, 2022
Sponsor
Shanghai Zhongshan Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05363722
Brief Title
A Clinical Study to Observe the Effectiveness and Safety of IBI310, Bevacizumab Combined With Sintilimab in the Treatment of Advanced Hepatocellular Carcinoma
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
May 2022 (Anticipated)
Primary Completion Date
April 2023 (Anticipated)
Study Completion Date
April 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Zhongshan Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm A（IBI310 0.5mg/kg）
Arm Type
Experimental
Arm Description
IBI310 0.5mg/kg IV d1 Q6W, sintilimab 200mg IV d1 Q3W, combined with bevacizumab 15mg/kg IV d1，Q3W
Arm Title
Arm B（IBI310 0.3mg/kg）
Arm Type
Experimental
Arm Description
IBI310 0.3mg/kg IV d1 Q6W, sintilimab 200mg IV d1 Q3W, combined with bevacizumab 15mg/kg IV d1，Q3W
Intervention Type
Drug
Intervention Name(s)
IBI310（0.5mg/kg）
Intervention Description
IBI310 0.5mg/kg IV d1 Q6W
Intervention Type
Drug
Intervention Name(s)
IBI310（0.3mg/kg）
Intervention Description
IBI310 0.3mg/kg IV d1 Q6W
Intervention Type
Drug
Intervention Name(s)
sintilimab
Intervention Description
sintilimab 200 mg IV d1 Q3W
Intervention Type
Drug
Intervention Name(s)
bevacizumab
Intervention Description
bevacizumab 15 mg/kg IV d1，Q3W
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
efficacy
Time Frame
The proportion of patients with complete response or partial response, through study completion, an average of 3 years
Secondary Outcome Measure Information:
Title
Duration of Response（DOR）according to RECIST V1.1 criteria
Description
efficacy
Time Frame
From date of randomization until the date of first documented progression, up to 48 months
Title
Duration of Response（DOR）according to mRECIST criteria
Description
efficacy
Time Frame
From date of randomization until the date of first documented progression, up to 48 months
Title
Disease Control Rate（DCR） according to RECIST V1.1 criteria
Description
efficacy
Time Frame
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
Title
Disease Control Rate（DCR） according to mRECIST criteria
Description
efficacy
Time Frame
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
Title
Time to Progression（TTP）according to RECIST V1.1 criteria
Description
efficacy
Time Frame
From date of randomization until the date of first documented progression, up to 48 months
Title
Time to Progression（TTP）according to mRECIST criteria
Description
efficacy
Time Frame
From date of randomization until the date of first documented progression, up to 48 months
Title
Progresison Free Surviva（PFS）according to RECIST V1.1 criteria
Description
efficacy
Time Frame
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
Title
Progresison Free Surviva（PFS）according to mRECIST criteria
Description
efficacy
Time Frame
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
Title
Overall survival (OS)
Description
efficacy
Time Frame
From date of randomization until death from any cause，through study completion, an average of 3 years
Title
Immune Best Overall Response（iBOR）according to iRECIST criteria
Description
efficacy
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
12. IPD Sharing Statement
Learn more about this trial
A Clinical Study to Observe the Effectiveness and Safety of IBI310, Bevacizumab Combined With Sintilimab in the Treatment of Advanced Hepatocellular Carcinoma
We'll reach out to this number within 24 hrs