Efficacy of Shipixiaoji Granules, Lenvatinib, and Tislelizumab in Patients with Unresectable Hepatocellular Carcinoma: Protocol for a Prospective, Single-Arm, Phase Ⅱ Trial

Background and Aim Shipixiaoji granules (SPXJ) is traditional Chinese medicine that treats hepatocellular carcinoma (HCC). However, its efficacy in HCC is still unknown. This prospective study assessed the outcomes of using SPXJ combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) in the management of patients with unresectable HCC. Methods This study was conducted as a single-arm phase II clinical trial. We recruited patients diagnosed with CNLC stage Ⅱ to Ⅲ HCC. The treatment regimen included oral lenvatinib (12 mg for patients weighing ≥60 kg; 8 mg for those weighing <60 kg) once daily, intravenous tislelizumab (200 mg) every 3 weeks, and SPXJ twice daily. The primary endpoint was defined as progression-free survival (PFS) in accordance with RECIST 1.1 criteria. Results Fifty-four patients were enrolled in this study. The primary endpoint was achieved, with a median PFS of 12.7 months. The objective response rate (ORR) was recorded at 55.6%. The disease control rate (DCR) was observed at 98.1%. Additionally, we compared PFS based on the participants’ sleep behavior. The results indicated that patients with a morning chronotype had a median PFS of 14.1 months, while those with a night chronotype had a median PFS of 9.85 months (95% CI: 1.366-6.853, P < .05). Treatment-related adverse events were reported in 96.3% (n = 52) of patients. Conclusions The combination of SPXJ, lenvatinib, and tislelizumab demonstrated substantial safety and anti-tumor efficacy as first-line treatment for unresectable HCC. Moreover, patients’ sleep behavior significantly influences treatment efficacy.