SHR-1701 Plus Apatinib for Second-Line Treatment in Targeted-Immune Pretreated Advanced Hepatocellular Carcinoma

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. Aged 18-75 years, male or female; signed informed consent form with good compliance; 2. Patients with histologically confirmed hepatocellular carcinoma or meeting clinical diagnostic criteria, currently unresectable or metastatic; 3. Prior receipt of first-line combined targeted and immunotherapy with subsequent disease progression or intolerance; 4. At least one measurable lesion meeting the criteria of RECIST v1.1; 5. ECOG performance status of 0 or 1; 6. Expected survival ≥ 12 weeks; 7. Child-Pugh Class A (score 5-6); 8. Adequate organ and bone marrow function as defined below (tested within 14 days prior to initiation of study treatment): 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 \