A phase Ib/II study of BLU-554, a fibroblast growth factor receptor 4 inhibitor in combination with CS1001, an anti-PD-L1, in patients with locally advanced or metastatic hepatocellular carcinoma

by Selleckchem | Aug 07 2023

Objective: Targeted therapy combined with immunotherapy has become the main treatment option for hepatocellular carcinoma (HCC). This trial assessed the safety and efficacy of fibroblast growth factor receptor 4 inhibitor (BLU-554) in combination with the anti-PD-L1 monoclonal antibody (CS1001) in patients with locally advanced or metastatic HCC.

Patients and methods: This Phase Ib/II trial enrolled patients with locally advanced or metastatic HCC who were FGF19-positive. The patients were intravenously administered with CS1001 (1200 mg) every three weeks and orally administered with BLU-554 (600 mg) daily. The primary endpoint was objective response rate (ORR), as assessed according to RECISTv1.1.

Results: Four patients were treated with BLU-554 combined with CS1001. The trial revealed a 50% ORR and 100% DCR. The main adverse reactions that were attributed to BLU-554 in combination with CS1001 were diarrhoea, liver function impairments and skin rashes. Only one patient had immune-related adverse reactions.

Conclusion: Preliminary data showed that BLU-554 in combination with CS1001 is safe and effective for treatment of patients with locally advanced or metastatic HCC.

Comments:

The objective of the trial was to evaluate the safety and efficacy of combining the fibroblast growth factor receptor 4 inhibitor (BLU-554) with the anti-PD-L1 monoclonal antibody (CS1001) in patients with locally advanced or metastatic hepatocellular carcinoma (HCC). The study specifically enrolled patients who were FGF19-positive.

The treatment regimen consisted of intravenous administration of CS1001 at a dose of 1200 mg every three weeks, along with oral administration of BLU-554 at a dose of 600 mg daily. The primary endpoint of the trial was the objective response rate (ORR), as determined by RECISTv1.1 criteria, which assesses tumor response.

Four patients were included in the study and received the combination therapy of BLU-554 and CS1001. The trial results showed a 50% ORR, indicating that half of the patients experienced a reduction in tumor size or complete disappearance of tumors. Additionally, the disease control rate (DCR), which represents the proportion of patients with stable disease or better, was 100%. This suggests that all patients in the trial had disease stabilization or a favorable response to the treatment.

The main adverse reactions associated with the combination of BLU-554 and CS1001 were diarrhea, liver function impairments, and skin rashes. However, only one patient experienced immune-related adverse reactions, indicating that the treatment was generally well-tolerated.

Based on these preliminary data, the combination therapy of BLU-554 and CS1001 appears to be both safe and effective for the treatment of patients with locally advanced or metastatic HCC. However, it's important to note that these results are based on a small number of patients, and further research and larger clinical trials are needed to validate these findings and establish the long-term safety and efficacy of this treatment approach.