A Randomized, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of IBI310 and Sintilimab Combination Therapy as First-line Treatment in Previously Untreated Patients With Unresectable or Metastatic Hepatocellular Carcinoma
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Innovent Biopharmaceutical Technology (Hangzhou) Co., LTD.
- Enrollment
- 680
- Locations
- 3
- Primary Endpoint
- Phase II: AEs（Adverse Event）
Overview
Brief Summary
This study is a randomized, controlled, open-label, multicenter, seamless Phase II/III trial designed to evaluate the efficacy and safety of the combination regimen of IBI310 and sintilimab in participants with locally advanced or metastatic hepatocellular carcinoma (HCC) who are: (1) treatment-naive to systemic therapy; and (2) either unsuitable for curative-intent surgical resection or local therapy, or have experienced disease progression following prior surgical resection or local therapy.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically or cytologically confirmed hepatocellular carcinoma (HCC).
- •Age ≥18 years and ≤75 years.
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or
- •Barcelona Clinic Liver Cancer (BCLC) staging of Stage C, or Stage B that is unsuitable for curative-intent surgery and/or locoregional therapy.
- •No prior systemic antineoplastic therapy for HCC before first dose.
- •At screening, per RECIST 1.1, there must be at least one measurable lesion that has not undergone local therapy, or a measurable lesion that has clearly progressed following local therapy (per RECIST 1.1).
- •Child-Pugh score ≤
- •Adequate organ and bone marrow function.
- •Expected survival ≥12 weeks at the time of treatment initiation.
- •Female participants of childbearing potential, or male participants whose sexual partners are of childbearing potential, must use effective contraception throughout the treatment period and for 15 months after the last dose of oxaliplatin (for females) / 12 months after the last dose of oxaliplatin (for males), or for 6 months after the last dose of any other investigational drug-whichever period ends later.
Exclusion Criteria
- •Histologically or cytologically confirmed diagnosis of fibrolamellar hepatocellular carcinoma (HCC), sarcomatoid HCC, cholangiocarcinoma, or other mixed hepatic malignancies containing these components.
- •History of hepatic encephalopathy or prior liver transplantation.
- •Clinically symptomatic pleural effusion, ascites, or pericardial effusion requiring therapeutic drainage; participants with only minimal (radiologically detected), asymptomatic effusions may be enrolled.
- •Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection:
- •Known central nervous system (CNS) metastases or symptomatic spinal cord compression.
- •Esophageal or gastric variceal bleeding due to portal hypertension within the past 6 months; Grade 3 (G3) esophageal/gastric varices documented by endoscopy within 3 months prior to first dose; or evidence of portal hypertension.
- •Life-threatening hemorrhagic event within the past 3 months, including but not limited to events requiring blood transfusion, surgical or local intervention, or ongoing pharmacologic hemostatic therapy.
- •Metastatic lesions invading major vessels, airways, or the mediastinum with clinically significant bleeding risk.
- •Arterial or venous thromboembolic event within the past 6 months, including myocardial infarction, unstable angina, cerebrovascular accident (stroke), transient ischemic attack (TIA), pulmonary embolism, deep vein thrombosis, or other severe thromboembolic conditions.
- •Portal vein tumor thrombus (PVTT) involving both the main portal vein and left/right branch; PVTT extending into the superior mesenteric vein; or PVTT involving the inferior vena cava.
Arms & Interventions
Treatment Group2
Sintilimab+ IBI310+Bevacizumab
Intervention: IBI310 (Biological)
Treatment Group3
Sintilimab+ IBI310+Oxaliplatin+Capecitabine
Intervention: IBI310 (Biological)
Treatment Group1
Sintilimab+ IBI310+Bevacizumab+Oxaliplatin+Capecitabine
Intervention: IBI310 (Biological)
Control Group
Sintilimab+ Bevacizumab
Intervention: Bevacizumab (Biological)
Treatment Group3
Sintilimab+ IBI310+Oxaliplatin+Capecitabine
Intervention: Capecitabine (Drug)
Treatment Group2
Sintilimab+ IBI310+Bevacizumab
Intervention: Sintilimab (Biological)
Treatment Group2
Sintilimab+ IBI310+Bevacizumab
Intervention: Bevacizumab (Biological)
Control Group
Sintilimab+ Bevacizumab
Intervention: Sintilimab (Biological)
Treatment Group3
Sintilimab+ IBI310+Oxaliplatin+Capecitabine
Intervention: Oxaliplatin (Drug)
Treatment Group1
Sintilimab+ IBI310+Bevacizumab+Oxaliplatin+Capecitabine
Intervention: Bevacizumab (Biological)
Treatment Group3
Sintilimab+ IBI310+Oxaliplatin+Capecitabine
Intervention: Sintilimab (Biological)
Treatment Group1
Sintilimab+ IBI310+Bevacizumab+Oxaliplatin+Capecitabine
Intervention: Oxaliplatin (Drug)
Treatment Group1
Sintilimab+ IBI310+Bevacizumab+Oxaliplatin+Capecitabine
Intervention: Sintilimab (Biological)
Treatment Group1
Sintilimab+ IBI310+Bevacizumab+Oxaliplatin+Capecitabine
Intervention: Capecitabine (Drug)
Outcomes
Primary Outcomes
Phase II: AEs（Adverse Event）
Time Frame: up to 2 years
Phase II: ORR （Objective Response Rate） assessed by investigator per RECIST 1.1.
Time Frame: up to 2 years
Phase II: PFS（Progression-Free Survival） assessed by investigator per RECIST 1.1.
Time Frame: up to 2 years
Phase II: TRAES（Treatment Emergent Adverse Event）
Time Frame: up to 2 years
Phase II: SAEs（Serious Adverse Event）
Time Frame: up to 2 years
Phase III: OS（Overall Survival）
Time Frame: up to 2 years
Phase III: PFS（Progression-Free Survival）assessed by the Independent Radiologic Review Committee (IRRC) per RECIST 1.1.
Time Frame: up to 2 years
Secondary Outcomes
- Phase II: OS(up to 2 years)
- Phase II: Incidence and characteristics of ADA&Nab.(up to 2 years)
- Phase II: DoR (Duration of Response )(up to 2 years)
- Phase II: DCR (Disease Control Rate )(up to 2 years)
- Phase II: TTR (Time to Response )(up to 2 years)
- Phase II:Cmax (maximum plasma concentration)(up to 2 years)
- Phase II:Tmax (time to reach maximum concentration)(up to 2 years)
- Phase II: AUC (time curve)(up to 2 years)
- PhaseIII: ORR （Objective Response Rate）assessed by IRRC according to RECIST1.1.(up to 2 years)
- PhaseIII: DoR （Duration of Response）assessed by IRRC according to RECIST1.1.(up to 2 years)
- PhaseIII: DCR （Time to Response）assessed by IRRC according to RECIST1.1.(up to 2 years)
- PhaseIII: TTR（Time to Response） assessed by IRRC according to RECIST1.1.(up to 2 years)
- PhaseIII: ORR （Objective Response Rate）assessed by the investigator according to RECIST1.1.(up to 2 years)
- PhaseIII: PFS （Progression-Free Survival）assessed by the investigator according to RECIST1.1.(up to 2 years)
- PhaseIII: DoR （Duration of Response）assessed by the investigator according to RECIST1.1.(up to 2 years)
- PhaseIII: DCR（Time to Response） assessed by the investigator according to RECIST1.1.(up to 2 years)
- PhaseIII: TTR (Time to Response) assessed by the investigator according to RECIST1.1.(up to 2 years)
- Phase III: ORR （Objective Response Rate）assessed by IRRC according to mRECIST.(up to 2 years)
- Phase III: PFS（Progression-Free Survival） assessed by IRRC according to mRECIST.(up to 2 years)
- Phase III: DoR（Duration of Response） assessed by IRRC according to mRECIST.(up to 2 years)
- Phase III: DCR（Disease Control Rate） assessed by IRRC according to mRECIST.(up to 2 years)
- Phase III: TTR（Time to Response） assessed by IRRC according to mRECIST.(up to 2 years)
- Phase III: incidence rate of AEs（Adverse Event）(up to 2 years)
- Phase III: incidence rate of TEAEs（Treatment Emergent Adverse Event）(up to 2 years)
- Phase III: incidence rate of SAEs（Serious Adverse Event）(up to 2 years)
- Phase III: Cmax(up to 2 years)
- Phase III: CL(Clearance)(up to 2 years)
- Phase III: t1/2 (Half-Life)(up to 2 years)
- Phase III: Volume(up to 2 years)
- Phase III: AUC (Area Under the Curve)(up to 2 years)
- Phase III: Incidence and characteristics of ADA&Nab.(up to 2 years)
- Phase II: Volume（PK）(up to 2 years)
- Phase II: t1/2 (Half-Life)(up to 2 years)
- phase III: score of (European Organization for Research and Treatment of Cancer, EORTC）EORTC QLQ-C30(up to 2 years)
- phase III: score of (Eropean Organization for Research and Treatment of Cancer, EORTC）EORTC QLQ-HCC18(up to 2 years)
- Phase II: CL (Clearance)(up to 2 years)