A Study to Evaluate SHR-1210 in Combination With Apatinib as First-Line Therapy in Patients With Advanced HCC
Condition: Locally Advanced or Metastatic and Unresectable HCC
Intervention: SHR-1210; Apatinib; Sorafenib
Intervention description: Subjects receive SHR-1210 intravenously, Dosage form: lyophilised powder, Strength: 200 mg /vial; Subjects receive Apatinib orally, Dosage form: tablet, Strength: 250 mg/tablet; Subjects receive Sorafenib orally, Dosage form: tablet, Strength: 0.2 g/tablet
Intervention MeSH terms: Sorafenib; Apatinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 543.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a randomized, open-label, international, multi-center, phase III trial to evaluate
      the efficacy and safety of SHR-1210 plus apatinib mesylate versus sorafenib as first-line
      therapy in patients with advanced HCC.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histopathologically or cytologically confirmed advanced HCC

          -  No previous systematic treatment for HCC

          -  Have at least one measurable lesion (in accordance with RECIST v1.1)

          -  BCLC stage B or C, and not suitable for surgical or local therapy, or has progressed
             following surgical and/or local therapy

          -  ECOG-PS score 0 or 1

          -  Child-Pugh Class: Grade A

          -  Life Expectancy of at least 12 weeks

          -  Subjects with HBV infection: HBV DNA<500 IU/ml or < 2500 copy/mL, and have received
             anti-HBV therapy for at least 14 days prior to enrollment in the study

          -  Subjects with HCV-RNA(+) must receive antiviral therapy

          -  Adequate organ function

        Exclusion Criteria:

          -  Known hepatocholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and lamellar
             cell carcinoma; other active malignant tumor except HCC within 5 years or
             simultaneously

          -  Moderate-to-severe ascites with clinical symptoms

          -  History of gastrointestinal hemorrhage within 6 months prior to the start of study
             treatment or clear tendency of gastrointestinal hemorrhage

          -  Abdominal fistula, gastrointestinal perforation or intraperitoneal abscess within 6
             months prior to the start of study treatment

          -  Known genetic or acquired hemorrhage or thrombotic tendency

          -  Thrombosis or thromboembolic event within 6 months prior to the start of study
             treatment

          -  Cardiac clinical symptom or disease that is not well controlled

          -  Hypertension that can not be well controlled through antihypertensive drugs

          -  Factors to affect oral administration

          -  History of hepatic encephalopathy

          -  Previous or current presence of metastasis to central nervous system

          -  HIV infection

          -  Combined hepatitis B and hepatitis C co-infection

          -  Be ready for or previously received organ or allogenic bone marrow transplantation

          -  Interstitial lung disease that is symptomatic or may interfere with the detection and
             management of suspected drug-related pulmonary toxicity

          -  Active known, or suspected autoimmune disease

          -  Subjects with a condition requiring systemic treatment with either corticosteroids or
             other immunosuppressive medications within 14 days of first administration of study
             treatment

          -  Use of potent CYP3A4 inducers or inhibitors within 2 weeks prior to the signature of
             ICF

          -  Known history of serious allergy to any monoclonal antibody or targeted
             anti-angiogenic drug

          -  Severe infection within 4 weeks prior to the start of study treatment

          -  Palliative radiotherapy for non-target lesions to control symptoms is allowed, but it
             must be completed at least 2 weeks prior to the start of study treatment

          -  Treatment of other investigational product(s) within 28 days prior to the start of
             study treatment