This clinical study aims to evaluate the efficacy and safety of Retlirafusp alfa Injection (SHR-1701) combined with apatinib in patients with advanced hepatocellular carcinoma (HCC) who have experienced disease progression after first-line targeted combined immunotherapy, and provide clinical evidence for the second-line treatment of advanced HCC. A total of 80 patients with radiologically or pathologically confirmed advanced/unresectable hepatocellular carcinoma with disease progression after prior first-line targeted-immunotherapy will be enrolled within 2.5 years. All enrolled patients will receive intravenous infusion of SHR-1701 at 30 mg/kg every 3 weeks in combination with oral apatinib 250 mg once daily; treatment will be maintained until disease progression or intolerable adverse toxicity occurs. The primary study endpoint is objective response rate (ORR).
Inclusion Criteria:
1)Hematology laboratory values (no blood transfusion, granulocyte colony-stimulating factor [G-CSF], or corrective hematologic agents administered within 14 days before screening): A. Hemoglobin (Hb) ≥ 90 g/L; B. Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; C. Platelet count (PLT) ≥ 75 × 10⁹/L; 2)Serum chemistry laboratory values (no albumin transfusion within 14 days before screening): A. Total serum bilirubin (BIL) ≤ 2 × ULN (≤ 3 × ULN for patients with Gilbert syndrome); B. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × ULN;
C. For patients with liver metastases, ALT and AST ≤ 5 × ULN; serum creatinine (Cr) ≤ 1.5 × ULN OR endogenous creatinine clearance ≥ 50 mL/min (calculated via the Cockcroft-Gault formula):
Male: Creatinine clearance = [(140 - age) × body weight] / (72 × serum Cr); Female: Creatinine clearance = [(140 - age) × body weight] / (72 × serum Cr) × 0.85(Body weight in kg; serum Cr in mg/dL) 9.Controllable proteinuria and blood pressure: urine protein <2+ (or 24-hour urinary protein <1.0 g, or urine protein/creatinine ratio [UPC] <1.0); systolic blood pressure ≤140 mmHg and diastolic blood pressure ≤90 mmHg (achievable with antihypertensive medications); 10.Evaluation of portal hypertension and varices: esophagogastroduodenoscopy (EGD) performed within 6 months prior to enrollment; patients with medium-to-high risk esophageal and gastric varices must have completed prophylactic treatment per guidelines (e.g., endoscopic variceal ligation [EVL]/non-selective beta-blockers [NSBB]), and study treatment shall be initiated no earlier than 14 days after EVL; 11.Hepatitis B and C criteria: For subjects with positive HBsAg or HBcAb, HBV-DNA shall be below the lower limit of quantification, and nucleos(t)ide antiviral therapy shall be initiated and administered throughout the study period. Subjects with HCV infection shall have stable virological status (either receiving DAA therapy or previously cured); 12.Fertility requirements: Fertile subjects agree to use reliable contraception from enrollment until 6 months after the last study drug administration, with a negative pregnancy test prior to enrollment; 13.Recovery from prior therapies: All toxicities related to previous anti-tumor therapies have recovered to Grade 1 or baseline levels (except acceptable alopecia, stable hypoendocrine function, etc.). At least 3 weeks have elapsed since the last systemic anti-tumor therapy, at least 4 weeks since major surgery, and at least 4 weeks since local therapy (TACE, RFA, etc.) with stable recovery.
Exclusion Criteria:
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All enrolled subjects receive SHR-1701 plus apatinib for the treatment of second-line advanced hepatocellular carcinoma, and observe efficacy and safety indicators.
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