Thermal ablation has been showed to induce immunogenic cell death and enhance the effect of anti-programmed death-1 (PD-1) in preclinical study. The open label phase I/II trial evaluated the safety and efficacy of ablation plus toripalimab (a humanized PD-1 antibody) in patients with advanced hepatocellular carcinoma (HCC). Phase I results on time scheduling, safety and preliminary antitumor activity are reported.
Patients who had advanced HCC after failure of a least one-line systemic therapy were included and randomized into 3 arms. In arm A, patients received toripalimab (240mg, Q3W) as monotherapy. In arm B, patients received subtotal ablation, defined as complete treatment of 1-5 lesions by thermal ablation and leave others lesions intact. Toripalimab (240mg, Q3W) was started on day 3 after ablation. In arm C, patients received toripalimab (240mg, Q3W) on day 14 after ablation.
Forty-eight patients (16 per arm) were included. Seventy five percent of patients experienced treatment-related adverse events (TRAE). The most common TREAs were mild (grade 1/2) and include influenza-like symptoms (25%), AST and/or ALT elevation (22.9%), hypothyroidism (22.9%), hypertension (16.6%), diarrhea (14.6%) and proteinuria (12.5%). Grade 3/4 TRAEs was reported in 18.7% of patients in arm A, 25.0% in arm B and C, respectively. One patient in arm A (6.3%) and one in arm B discontinued toripalimab treatment because of TRAE. No TRAE led to death. By the cutoff date, the objective response rate (ORR) was 18.8% in arm A, 37.5% in arm B and 31.2% in arm C. In arm B, 2 patients (12.5%) achieved complete response (CR). Initiating toripalimab treatment on day 3 after ablation was recommended for phase II evaluation.
The combination of subtotal thermal ablation and toripalimab was tolerable and showed promising antitumor activity in advanced HCC, especially with optimal schedule.
Clinical trial identification
Legal entity responsible for the study
Xiangya Hospital, Central South University.
TopAlliance Biosciences Inc.
All authors have declared no conflicts of interest.