Hepatocellular Carcinoma
Conditions
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.
Interventions
DRUGIBI310（0.5mg/kg）
IBI310 0.5mg/kg IV d1 Q6W
DRUGIBI310（0.3mg/kg）
IBI310 0.3mg/kg IV d1 Q6W
DRUGsintilimab
sintilimab 200 mg IV d1 Q3W
DRUGbevacizumab
bevacizumab 15 mg/kg IV d1，Q3W
Sponsors
Shanghai Zhongshan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | The proportion of patients with complete response or partial response, through study completion, an average of 3 years | efficacy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response（DOR）according to mRECIST criteria | From date of randomization until the date of first documented progression, up to 48 months | efficacy |
| Disease Control Rate（DCR） according to RECIST V1.1 criteria | 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 | efficacy |
| Disease Control Rate（DCR） according to mRECIST criteria | 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 | efficacy |
| Time to Progression（TTP）according to RECIST V1.1 criteria | From date of randomization until the date of first documented progression, up to 48 months | efficacy |
| Duration of Response（DOR）according to RECIST V1.1 criteria | From date of randomization until the date of first documented progression, up to 48 months | efficacy |
| Progresison Free Surviva（PFS）according to RECIST V1.1 criteria | 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 | efficacy |
| Progresison Free Surviva（PFS）according to mRECIST criteria | 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 | efficacy |
| Overall survival (OS) | From date of randomization until death from any cause，through study completion, an average of 3 years | efficacy |
| Immune Best Overall Response（iBOR）according to iRECIST criteria | 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 | efficacy |
| Time to Progression（TTP）according to mRECIST criteria | From date of randomization until the date of first documented progression, up to 48 months | efficacy |
Outcome results
None listed