Inclusion Criteria:
1. Patients voluntarily participate in this study and sign the informed consent form;
2. Aged ≥ 18 years (calculated as of the date of signing the informed consent form), male or female;
3. Pathologically or clinically confirmed hepatocellular carcinoma (HCC);
4. Have previously received at least one or more lines of systemic therapy (targeted therapy with or without immunotherapy);
5. Barcelona Clinic Liver Cancer (BCLC) stage B or C, unsuitable for surgery or local treatment, or progressed after surgery and/or local treatment;
6. Local treatment (including but not limited to surgery, radiotherapy, hepatic artery embolization, transcatheter arterial chemoembolization \[TACE\], hepatic artery infusion, radiofrequency ablation, cryoablation, or percutaneous ethanol injection) must have been completed at least 4 weeks before the baseline imaging scan (palliative radiotherapy requires only 2 weeks), and toxic reactions caused by local treatment (except alopecia) must have recovered to ≤ Grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0);
7. Presence of measurable lesions meeting the modified Response Evaluation Criteria in Solid Tumors (mRECIST) on baseline imaging;
8. Child-Pugh liver function class A;
9. Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-1;
10. Expected survival time \> 3 months;
11. Basic normal function of major organs, without severe abnormalities in blood, heart, lung, liver, kidney, bone marrow, or immunodeficiency diseases, meeting the protocol requirements:
1. Blood routine examination: (except hemoglobin; no blood transfusion, no use of granulocyte colony-stimulating factor \[G-CSF\] within 14 days before screening, and no corrective treatment within 7 days) i. Hemoglobin ≥ 90 g/L; ii. Neutrophil count ≥ 1.5×10\^9/L; iii. Platelet count ≥ 50×10\^9/L;
2. Biochemical examination: (no albumin transfusion within 14 days) i. Serum albumin ≥ 29 g/L; ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×upper limit of normal (ULN); iii. Total bilirubin (TBIL) ≤ 1.5×ULN; iv. Creatinine (Cr) ≤ 1.5×ULN or creatinine clearance \> 50 mL/min (calculated using the Cockcroft-Gault formula as follows): For males: Creatinine clearance = ((140 - age) × weight) / (72 × serum Cr) For females: Creatinine clearance = ((140 - age) × weight) / (72 × serum Cr) × 0.85 (Weight unit: kg; Serum Cr unit: mg/mL) v. Urinary protein \< 2+; if urinary protein ≥ 2+, a 24-hour urinary protein quantification can be performed, and patients with 24-hour urinary protein quantification \< 1.0 g are eligible for enrollment;
3. Coagulation function: Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5×ULN (patients receiving stable-dose anticoagulant therapy such as low-molecular-weight heparin or warfarin with INR within the expected therapeutic range of anticoagulants can be screened);
4. Thyroid-stimulating hormone (TSH) ≤ ULN; if abnormal, triiodothyronine (T3) and thyroxine (T4) levels should be examined, and patients with normal T3 and T4 levels are eligible;
12. Patients with active hepatitis B virus (HBV) infection who are willing to receive full-course antiviral therapy during the study (according to local standard treatment, such as entecavir) may be eligible for enrollment based on the doctor's judgment of individual patient conditions under viral load monitoring;
13. Patients with positive hepatitis C virus (HCV) ribonucleic acid (RNA) must receive antiviral therapy according to local standard treatment guidelines, and liver function elevation must be within CTCAE Grade 1;
14. Female patients of childbearing potential: Must agree to abstain from heterosexual intercourse or use reliable and effective contraception from the signing of the informed consent form until at least 120 days after the last dose of the study drug. Additionally, serum human chorionic gonadotropin (HCG) must be negative within 7 days before the start of study treatment; and must be non-lactating. A female patient is considered to have childbearing potential if she has menstruated, has not reached postmenopausal status (amenorrhea for ≥ 12 consecutive months with no other identified causes except menopause), and has not undergone sterilization (such as hysterectomy, bilateral salpingectomy, or bilateral oophorectomy);
15. Male patients whose partners are women of childbearing potential must agree to abstain from heterosexual intercourse or use reliable and effective contraception from the signing of the informed consent form until at least 120 days after the last dose of the study drug. Male subjects must also agree not to donate sperm during the same period. Male subjects whose partners are pregnant must use condoms and do not need to adopt other contraceptive methods.
Exclusion Criteria:
1. Previously received PD-L1 immunotherapy or apatinib targeted therapy;
2. No clear tumor-feeding artery identifiable by angiography;
3. Known cholangiocellular carcinoma, sarcomatoid HCC, mixed-cell carcinoma, or fibrolamellar carcinoma; having other active malignant tumors (except HCC) within 5 years or concurrently. Locally cured tumors such as basal cell carcinoma of the skin, cutaneous squamous cell carcinoma, superficial bladder cancer, carcinoma in situ of the prostate, carcinoma in situ of the cervix, and carcinoma in situ of the breast are eligible for enrollment;
4. Allergic to the investigational drugs;
5. Complicated with other malignant tumors, except for the following cases: malignant tumors treated with curative therapy, with no known active disease for ≥ 5 years before the first study intervention and low potential risk of recurrence; basal cell carcinoma of the skin, cutaneous squamous cell carcinoma, or lentigo maligna with potentially radical treatment; or carcinoma in situ with adequate treatment and no evidence of disease;
6. A history of hepatic encephalopathy;
7. Received other investigational drug treatments within 28 days or 5 half-lives (whichever is longer) before the start of study treatment;
8. Complicated with severe infection;
9. Any evidence of disease as judged by the investigator (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, active hemorrhagic diseases, active infections, active interstitial lung disease/pulmonary inflammation, severe chronic gastrointestinal diseases related to diarrhea, mental illness/social conditions) or a history of allogeneic organ transplantation that the investigator considers makes the subject unfit to participate in the study or affects compliance with the study protocol;
10. Active or previously documented autoimmune or inflammatory diseases (including inflammatory bowel diseases \[e.g., colitis or Crohn's disease\], diverticulitis \[excluding diverticulosis\], systemic lupus erythematosus, sarcoidosis syndrome, Wegener's syndrome \[granulomatosis with polyangiitis\], Graves' disease, rheumatoid arthritis, hypophysitis, and uveitis, etc.);
11. Known positive HIV test (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical assessment may include clinical history, physical examination, and imaging findings, or tuberculosis testing according to local practices).
