Abstract 173P
Background
This phase II trial was conducted to investigate the efficacy and safety of donafenib (a tyrosine-kinase inhibitor derived from sorafenib) plus sintilimab (a PD-1 inhibitor) for advanced stage hepatocellular carcinoma (HCC).
Methods
This was a single-center, single-arm phase II trial. The key eligibility criteria were as follows: age ≥ 18 years; BCLC stage C HCC; at least one target lesion based on mRECIST and RECIST 1.1; Eastern Cooperative Oncology Group performance status ≤ 1; Child-Pugh score ≤ 7; without involvement of the main portal vein or vena cava; without central nervous system involvement; no prior systemic therapy; and without history of organ or cell transplantation. The study was conducted in two parts. Part 1 (safety run-in): Six patients (pts) received donafenib 200 mg P.O. BID and sintilimab 200 mg I.V. Q3W. If there were 2 or more pts experienced donafenib-related dose-limiting toxicities (DLTs), the dose of donafenib would be adjusted to be 200 mg P.O. QD. Part 2: The subsequently enrolled pts received donafenib at the recommended dose determined from Part 1 and sintilimab 200mg I.V. Q3W. The primary endpoint was progression-free survival (PFS) per mRECIST.
Results
30 pts were enrolled in this study. Among them, 24 (80.0%) had macrovascular invasion, 19 (63.3%) had extrahepatic metastasis and 16 (53.3%) had intrahepatic tumor number > 3. The mean largest tumor diameter was 8.9±3.8 cm. In the safety run-in phase, 3 pts (50.0%) suffered from DLTs. And the dose of donafenib was reduced to 200 mg QD. Till cutoff date (August 31, 2023), the median follow-up for the pts was 16.0 months. The median PFS was 6.2 (95% confidence interval [CI]: 4.4-8.0) and 6.3 (95% CI: 5.4-7.2) months per mRECIST and RECIST 1.1, respectively. The objective response rate was 23.3% and 16.7% per mRECIST and RECIST 1.1, respectively. The median overall survival was 16.0 (95% CI: 13.5-18.5) months. TRAEs occurred in 28 pts (93.3%) and grade 3 TRAEs were observed in 9 pts (30.0%). There were no grade 4/5 TRAEs.
Conclusions
Donafenib plus sintilimab showed promising clinical benefits and was tolerated in pts with advanced stage HCC. The preliminary findings need to be verified by phase III randomized trials.
Clinical trial identification
NCT05162352.
Legal entity responsible for the study
The authors.
Funding
The National Natural Science Foundation of China (82172043 and 82202273), the Plan on Enhancing Scientific Research in GMU, the Innovative Clinical Technique of Guangzhou, the Featured Clinical Technique of Guangzhou, the Basic and Applied Basic Research Foundation of Guangdong Province (2020A1515110654), and the Clinical Study Project of the Second Affiliated Hospital of Guangzhou Medical University (2021-LCYJ-DZX-01, 2022-LCYJ-YY-02, 2022-LCYJ-YYDZX-01, and 2023-LCYJ-ZF-47).
Disclosure
All authors have declared no conflicts of interest.