Donafenib combined with sintilimab for advanced hepatocellular carcinoma: a single arm phase II trial
Xiaoyang Hong1,2, Yongjian Guo1, Wenbo Shi1,3
1Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Background:
Previous studies evaluating antiangiogenic agents plus immune checkpoint inhibitors for unresectable hepatocellular carcinoma (HCC) have shown encouraging results. This study was conducted to investigate the efficacy and safety of donafenib combined with sintilimab (Don-Sin) for advanced HCC.
Methods:
This was a single-center, single-arm phase II trial recruiting patients with BCLC stage C HCC. A safety run-in cohort was planned with the first 6 patients receiving oral donafenib 200 mg twice daily and intravenous sintilimab 200 mg once every 3 weeks. Dose-limiting toxicities (DLTs) were evaluated to determine the recommended dose of donafenib for those enrolled thereafter. The primary endpoint of this study was progression-free survival (PFS) per mRECIST.
Results:
30 patients were enrolled. As 3 patients (50.0%) experienced DLTs during safety run-in, the initial dose of donafenib was adjusted to 200 mg once daily for subsequent patients. The primary endpoint was met with a median PFS of 6.2 (95% confidence interval [CI], 4.4-8.0) months per mRECIST (6.3 [95% CI, 5.4-7.2] months per RECIST 1.1). The objective response rate was 23.3% per mRECIST and 16.7% per RECIST 1.1, while the disease control rate reached 76.7% per mRECIST/RECIST 1.1. The median overall survival was 16.0 (95% CI, 13.5-18.5) months. Treatment-related adverse events (TRAEs) occurred in 28 patients (93.3%) and grade 3 TRAEs were observed in 9 patients (30.0%).
Conclusions:
Don-Sin showed promising antitumor effects with an acceptable safety profile in patients with advanced stage HCC. The preliminary findings need to be further evaluated in phase III randomized controlled trials.
Trial Registration:
ClinicalTrials.gov (identifier: NCT05162352; date of registration: December 4, 2021).
Insights
Donafenib combined with sintilimab (Don-Sin) demonstrated promising antitumor effects for advanced hepatocellular carcinoma (HCC). This combination therapy showed a median progression-free survival of 6.2 months with an acceptable safety profile.
Area of Science:
- Oncology
- Immunotherapy
- Hepatocellular Carcinoma Research
Background:
- Previous studies indicate antiangiogenic agents combined with immune checkpoint inhibitors yield encouraging outcomes in unresectable HCC.
- Donafenib plus sintilimab (Don-Sin) is being investigated for advanced HCC treatment.
Purpose of the Study:
- To investigate the efficacy and safety of donafenib combined with sintilimab for advanced hepatocellular carcinoma (HCC).
Main Methods:
- A single-center, single-arm phase II trial enrolled patients with BCLC stage C HCC.
- A safety run-in cohort determined the recommended dose of donafenib (200 mg once daily) combined with sintilimab (200 mg every 3 weeks) after dose adjustments.
- The primary endpoint was progression-free survival (PFS) assessed per modified RECIST (mRECIST).
Main Results:
- The study enrolled 30 patients, with a median PFS of 6.2 months (mRECIST).
- Objective response rate was 23.3% (mRECIST), and disease control rate reached 76.7%.
- Median overall survival was 16.0 months, with 93.3% experiencing treatment-related adverse events (TRAEs), including 30.0% with grade 3 TRAEs.
Conclusions:
- Don-Sin exhibited promising antitumor activity and an acceptable safety profile in advanced HCC patients.
- Further evaluation in phase III randomized controlled trials is warranted.
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