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).
Aged 18-75 years, male or female; signed informed consent form with good compliance;
Patients with histologically confirmed hepatocellular carcinoma or meeting clinical diagnostic criteria, currently unresectable or metastatic;
Prior receipt of first-line combined targeted and immunotherapy with subsequent disease progression or intolerance;
At least one measurable lesion meeting the criteria of RECIST v1.1;
History of severe hypersensitivity or irreversible toxic reactions to similar PD-L1 agents or VEGFR-2 TKIs;
Child-Pugh Class B or C, refractory ascites requiring paracentesis at least weekly, Grade ≥2 hepatic encephalopathy, or MELD score >12 (optional, subject to institutional SOPs);
High bleeding risk: Grade ≥3 gastrointestinal hemorrhage, perforation, active ulcer or uncontrolled bleeding diathesis within the past 6 months; untreated medium-to-large varices or high-risk signs identified on EGD without completed prophylactic intervention; clinical indication for potent anticoagulants or dual antiplatelet therapy that cannot be discontinued or substituted (aspirin ≤100 mg daily may be permitted at the Investigator's discretion);
Prior treatment with apatinib or PD-L1 monoclonal antibody immune checkpoint inhibitors;