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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: IBI310（0.5mg/kg）; Drug: sintilimab; Drug: bevacizumab; Drug: IBI310（0.3mg/kg）

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically/cytologically confirmed hepatocellular carcinoma, or meeting the clinical diagnostic criteria for hepatocellular carcinoma ;
2. Aged ≥18 years,≤75 years;
3. ECOG performance status score of 0 or 1 point;
4. Barcelona Clinic Liver Cancer (BCLC) stage C, or Stage B not suitable for radical surgery and/or local treatment;
5. No systemic antitumor treatment for hepatocellular carcinoma before the first administration;
6. 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);
7. Child-Pugh Class A or B(≤7);
8. Adequate organ and bone marrow function.
9. Expected life time is over 12 weeks.
10. Take effective contraceptive measures
11. Willing to attend the study and having given the ICF

Exclusion Criteria:

1. Known fibrolamellar HCC, sarcomatoid HCC, mixed cholangiocarcinoma and HCC
2. History of hepatic encephalopathy or liver transplantation
3. Pleural, ascites, and pericardial effusion with clinical symptoms requiring drainage
4. HBV-DNA>2000 IU/ML or 10^4 copies/ml；Untreated positive HCV-RNA；HbsAg and anti-HCV antibody were both positive
5. History of GI bleeding within 6 months, or severe (G3) varices at endoscopy within 3 months
6. Arteriovenous embolism within 6 months
7. The tumor thrombus involved both main and branch portal veins, main portal veins and mesenteric veins or inferior vena cava.
8. Antiplatelet drugs were administered for 10 days for therapeutic purposes 2 weeks before administration
9. Uncontrolled hypertension
10. Unrecovered AE（>CTCAE grade 1） due to previous treatment
11. Heart failure (NYHA Classification III-IV), or poorly controlled arrhythmias
12. History of gastrointestinal perforation, fistula, intestinal obstruction, extensive bowel resection, Crohn's disease, ulcerative colitis, or chronic diarrhea
13. With lung fibrosis, interstitial lung disease, pneumoconiosis, drug-associated pneumonia and serious impairment in lung function
14. Active tuberculosis
15. Infected with HIV or syphilis
16. Severe infections that are active or clinically poorly controlled
17. Use of immunosuppressive drugs within 4 weeks prior to initial dosing
18. Receipt of live attenuated vaccine within 4 weeks prior to randomization
19. Significant traumatic injury or major surgical procedure within 28 days prior to randomization
20. Other conditions that the investigator judged inappropriate for inclusion
21. Prior immunotherapy or targeted therapy
22. Treatment of Traditional Chinese medicine with anti-tumor indications or drugs with immunomodulatory effects whitin 2 weeks
23. Pregnant or breast-feeding women

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2022
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: April 14, 2022
• First Submitted That Met QC Criteria: May 5, 2022
• First Posted (Actual): May 6, 2022

Study Record Updates

• Last Update Posted (Actual): May 6, 2022
• Last Update Submitted That Met QC Criteria: May 5, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: CIBI310Y001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No