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

Hepatocellular Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05363722
• Other study ID #: CIBI310Y001
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: May 2022
• Est. completion date: April 2024

Study information

• Verified date: May 2022
• Source: Shanghai Zhongshan Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: April 2024
• Est. primary completion date: April 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• IBI310(0.5mg/kg)
IBI310 0.5mg/kg IV d1 Q6W
• IBI310(0.3mg/kg)
IBI310 0.3mg/kg IV d1 Q6W
• sintilimab
sintilimab 200 mg IV d1 Q3W
• bevacizumab
bevacizumab 15 mg/kg IV d1,Q3W

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Zhongshan Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR)	efficacy	The proportion of patients with complete response or partial response, through study completion, an average of 3 years
Secondary	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
Secondary	Duration of Response(DOR)according to mRECIST criteria	efficacy	From date of randomization until the date of first documented progression, up to 48 months
Secondary	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
Secondary	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
Secondary	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
Secondary	Time to Progression(TTP)according to mRECIST criteria	efficacy	From date of randomization until the date of first documented progression, up to 48 months
Secondary	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
Secondary	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
Secondary	Overall survival (OS)	efficacy	From date of randomization until death from any cause,through study completion, an average of 3 years
Secondary	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