974P - Surufatinib combined with anti-PD-1/PD-L1 antibody in the second-line or monotherapy in third-line treatment of advanced hepatocellular carcinoma: A single-arm, open-label, multi-center phase II study

Background

Surufatinib (SUR, a selective VEGFRs, FGFR1 and CSF-1R inhibitor) has dual effects of anti-angiogenesis and immunomodulation. The combination of surufatinib and anti-PD-1/PD-L1 antibody may have a good synergistic mechanism.

Methods

This single-arm, open-label, multi-center phase II clinical study (NCT05282433) comprises two cohorts of patients aged 18-75 with unresectable HCC, BCLC Stage B or C, and Child-Pugh A or B classification. Cohort 1: Patients received surufatinib (250 mg, qd, po, q3w) plus anti- PD-1/PD-L1 antibody (q3w) as second-line therapy. Cohort 2: Patients received surufatinib (300 mg, qd, po, q3w) as third-line monotherapy. The primary endpoint was PFS, the secondary endpoints included OS, ORR, DCR and safety.

Results

As of April 25, 2024, 15 pts in cohort 1 (median age 52, 73.3% male, 100% BCLC Stage C, 86.7% Child-Pugh A, 60% with AFP ≥400 μg/L, 33.3% with vascular invasion, 80% with lung metastases) and 9 patients in cohort 2 (median age 59, 88.9% male, 100% BCLC Stage C, 100% Child-Pugh A, 33.3% with AFP ≥400 μg/L, 11.1% with vascular invasion, 44.4% with extrahepatic lymph node metastasis, 44.4% with lung metastases) were enrolled. Median PFS was 5.2 months in cohort 1 and 4.4 months in cohort 2. ORR was 20.0% in cohort 1 and 11.1% in cohort 2, while DCR was 73.3% and 88.9%, respectively. Subgroup analysis showed that pts with AFP <400 μg/L (cohort1: 8.4 months; cohort 2: 7.0 months), no previous interventional therapy (cohort1: 5.2 months; cohort 2: 6.0 months) were associated with longer PFS in two cohorts. Grade ≥3 TRAEs were thrombocytopenia (16.7%) and leukopenia (12.5%). No new safety signals occurred.

Conclusions

Surufatinib demonstrated promising efficacy and manageable safety in advanced HCC, especially in patients with lower AFP levels and no previous interventional or sorafenib treatments. Further research in a larger population is necessary to confirm these findings. The trial continues, with more data anticipated.

Clinical trial identification

NCT05282433.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Zhongnan Hospital, Wuhan University, Wuhan, China.

Disclosure

All authors have declared no conflicts of interest.