Data from A Phase 1/2 Multicenter Randomized Trial of Local Ablation Plus Toripalimab Versus Toripalimab Alone for Previously Treated Unresectable Hepatocellular Carcinoma

Abstract Purpose: To assess the safety and efficacy of local ablation plus PD-1 inhibitor toripalimab in previously treated unresectable hepatocellular carcinoma (HCC). Patients and Methods: In the multicenter, two-stage, and randomized phase 1/2 trial, patients were randomly assigned to receive toripalimab alone (240mg, every 3 weeks), subtotal local ablation followed by toripalimab starting on post-ablation day 3 (Schedule D3) or on post-ablation day 14 (Schedule D14). The first endpoint of stage 1 was to determine which combination schedule could continue and progression-free survival (PFS) as the primary endpoint for stage 1/2. Results: A total of 146 patients were recruited. During stage 1, Schedule D3 achieved numerically higher objective response rate than Schedule D14 for non-ablation lesions (37.5% versus 31.3%), and was chosen for stage 2 evaluation. For the entire cohort of both stages, patients with Schedule D3 had a significantly higher objective response rate than with toripalimab alone (33.8% versus 16.9%, P = 0.027). Moreover, patients with Schedule D3 had improved median PFS (7.1 months versus 3.8 months, P ﹤0.001) and median overall survival (18.4 months versus 13.2 months, P = 0.005), as compared with toripalimab alone. In addition, six (9%) patients with toripalimab, 8 (12%) with Schedule D3, and 4 (25%) with Schedule D14 developed grade 3 or 4 adverse events, and one patient (2%) with Schedule D3 manifested grade 5 treatment-related pneumonitis. Conclusions: In patients with previously treated unresectable HCC, subtotal ablation plus toripalimab improved the clinical efficacy as compared with toripalimab alone with an acceptable safety profile.