Overview

This study is a single-arm prospective clinical trial that enrolled 94 patients with unresectable hepatocellular carcinoma(HCC) who received first-line treatment with tislelizumab combined with Huaier granule. By comparing the objective response rate (ORR) and other data with those from the historical Rational 301 study, the study aims to explore the efficacy and safety of tislelizumab combined with Huaier granule as a first-line treatment for unresectable HCC, as well as its potential to improve patients' quality of life and alleviate HCC-related symptoms.

Eligibility

Inclusion Criteria:

1. Male or female aged ≥18 years at the time of signing the informed consent form;
2. Histologically confirmed diagnosis of HCC;
3. BCLC stage C, or BCLC stage B disease that is unsuitable for locoregional therapy or has progressed after locoregional therapy, and is not eligible for curative treatment;
4. No prior systemic therapy for HCC. Note: Patients who have previously received local therapy (e.g., TACE) are not excluded;
5. Presence of ≥1 measurable lesion according to RECIST v1.1, provided that: the selected target lesion(s) have not been previously treated with local therapy, or the selected target lesion(s) are located within an area of prior local treatment and have subsequently been assessed as progressive disease according to RECIST v1.1;
6. Child-Pugh class A liver function within 7 days prior to randomization;
7. ECOG performance status ≤1.

Exclusion Criteria:

1. Fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, or mixed hepatocellular-cholangiocarcinoma;
2. Tumor thrombus involving the main portal vein or inferior vena cava;
3. Prior local liver therapy (e.g., transarterial chemoembolization, transarterial embolization, hepatic arterial infusion, radiotherapy, radioembolization, or ablation) or any immunotherapy (e.g., interleukin, interferon, thymosin, etc.) within 28 days before enrollment;
4. Use of traditional Chinese medicine or patent drugs for cancer control within 14 days before enrollment;
5. Grade 2 or higher hepatic encephalopathy at screening or in medical history;
6. Presence of pericardial effusion, uncontrolled pleural effusion, or clinically significant ascites at screening, defined as meeting either of the following criteria: (a) ascites detectable by physical examination at screening, or (b) ascites requiring paracentesis during screening;
7. History of severe hypersensitivity to other monoclonal antibodies;
8. Any clinical evidence of portal hypertension with bleeding esophageal or gastric varices during screening or within 6 months before randomization;
9. Toxicities from prior anticancer therapy have not resolved to baseline or stabilized, except for alopecia;
10. Any hemorrhagic or thrombotic disease within 6 months before screening, or any anticoagulant therapy requiring monitoring of the international normalized ratio (e.g., warfarin or similar agents);
11. History of any active malignancy within 2 years before screening, except for HCC under study in this trial and locally recurrent cancers that have been curatively treated (e.g., resected basal cell or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast);
12. Known central nervous system metastases and/or leptomeningeal disease at screening;
13. Any active immunodeficiency or autoimmune disease at screening, and/or history of any immunodeficiency or autoimmune disease with potential for recurrence;
14. Any condition requiring systemic corticosteroid therapy (at doses \>10 mg/day prednisone or equivalent of similar drugs) or other immunosuppressive treatment within 14 days before screening;
15. History of interstitial lung disease or non-infectious pneumonia, unless radiation-induced;
16. Any severe chronic or active infection requiring systemic antibacterial, antifungal, or antiviral therapy at screening (e.g., tuberculosis), excluding viral hepatitis; known history of human immunodeficiency virus infection;
17. Presence of underlying medical conditions that, in the investigator's judgment, may pose risks for receiving the study treatment or complicate the interpretation of adverse events/toxicity;
18. History of allogeneic stem cell transplantation or organ transplantation; receipt of any live vaccine within 4 weeks before randomization (Note: seasonal influenza vaccines are generally inactivated and allowed; intranasal vaccines are live and not allowed);
19. Any major surgery within 28 days before randomization;
20. Female patients who are lactating.