Combination of donafenib and anti-PD-1 antibody plus trans-arterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (uHCC).

e16197 Background: Donafenib (Dona), a multikinase inhibitor recently marketed in China for advanced HCC with its superiority in overall survival (OS) over Sorafenib from a large head-to-head Phase 3 study. The clinical experience of triple therapy (TKIs + ICIs + TACE) in the treatment of patients (pts) with uHCC is limited. We assessed the safety and efficacy of triple therapy [Dona +anti-PD-1+ TACE] in uHCC in this Phase 1 study. Methods: The objective of this Phase 1, open-label, multicenter, dose-escalation and expansion study was to assess the MTD/recommended dose for Dona in combination of a fixed-dose anti-PD-1 plus TACE in uHCC. The primary endpoint was DLT occurring in the first treatment cycle. Secondary endpoints included the overall safety and tolerability, ORR and PFS by mRECIST. Qualified pts (age 18-75) were enrolled if uHCC without macrovascular invasion (VP3/4) or extrahepatic spread; measurable disease by mRECIST; ECOG 0 to 1; Child-Pugh A; systemic therapy naive. Results: At the cut-off date (Dec 31 2021), data of 25 pts who underwent triple therapy from 6 cancer centers in China were analyzed (Table). The median duration of follow-up was 105 days (1-358 days). No DLTs were observed [Dona 50 mg Bid (n=3); 150 mg Qd (n=3); 100 mg Bid (n=6)]. Additional 13 pts were treated with the recommended dose of Dona 100 mg Bid. Treatment-related adverse events (TRAE) occurred in 24 pts (Grade 3, 36%; no Grade 4). 16 pts had at least one response assessment, the ORR was 62.5%; in 12 pts with BLCL B, the ORR was 83.3%. mPFS was not reached. Conclusions: Combination of Dona, anti-PD-1 and TACE showed a high rate of tumor response and good safety profile in uHCC. Clinical trial information: NCT04605185. [Table: see text]