Efficacy and safety of tislelizumab plus lenvatinib as first-line treatment in patients with unresectable hepatocellular carcinoma: a multicenter, single-arm, phase 2 trial

Abstract Background Lenvatinib is widely used in treatment of unresectable hepatocellular carcinoma (uHCC), but the benefit of its combination with immunotherapy needs to be verified. This study evaluated the efficacy and safety of tislelizumab plus lenvatinib in systemic treatment-naïve patients with uHCC. Methods In this multicenter, single-arm, phase 2 study, systemic treatment-naïve patients with uHCC received tislelizumab 200 mg every three weeks plus lenvatinib (bodyweight ≥ 60 kg: 12 mg; < 60 kg: 8 mg; once daily). Dose-limiting toxicities (DLTs) were evaluated in safety run-in phase to determine whether to enter the expansion phase. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Based on Simon’s two-stage design, > 6 responders were needed in stage 1 ( n = 30) to continue the study, and ≥ 18 responders were needed by the end of stage 2 ( n = 60) to demonstrate statistical superiority to a historical control of lenvatinib monotherapy. Results Sixty-four patients were enrolled. No DLTs were reported. The study achieved statistical superiority ( p = 0.0003) with 23 responders assessed by IRC per RECIST v1.1 in the first 60 patients of the efficacy evaluable analysis set ( n = 62). After a median follow-up of 15.7 months, confirmed ORR and disease control rate were 38.7% (24/62, 95% confidence interval [CI], 26.6–51.9) and 90.3% (56/62, 95% CI, 80.1–96.4), respectively. Median progression-free survival was 8.2 months (95% CI, 6.8–not evaluable). Overall survival rate at 12 months was 88.6% (95% CI, 77.7–94.4). Grade ≥ 3 treatment-related adverse events occurred in 18 (28.1%) patients. Conclusions Tislelizumab plus lenvatinib demonstrated promising antitumor activity with favourable tolerability as first-line therapy for patients with uHCC. Trial registration ClinicalTrials.gov (NCT 04401800).