950P - Phase II clinical study of sorafenib combined with tislelizumab in the treatment of first-line unresectable hepatocellular carcinoma and the predictive effect and correlation of CTC

Background

In this study, we aimed to evaluate the safety and efficacy of combining PD-1 antibody Tislelizumab with Sorafenib for the treatment of advanced hepatocellular carcinoma(HCC). Additionally, we sought to investigate the relationship between the circulating tumor cells (CTCs) count/ programmed death-ligand 1 (PD-L1) expression of CTCs and the prognosis of patients with advanced hepatocellular carcinoma.

Methods

The study Enrolled patients (pts) with unresectable HCC patients (pts) to receive tislelizumab combined with sorafenib. Tislelizumab, 200mg/q3w intravenous infusion, sorafenib 400 mg/bid oral dose; Evaluate every 3 cycles (9 weeks) to evaluate the safety and effectiveness of the drug regimen CTCs count and PD-L1 expression of CTCs were performed in all patients before enrollment. Primary endpoint was ORR by RECISTv1.1 per investigators. The secondary endpoints aimed to assess the relationship between the count of CTCs or the expression of PD-L1 and the prognosis of HCC.

Results

As of November 2022, 32 patients were enrolled in the study received combination treatment. For 32 pts, ORR was 17% (95% CI 33.0%-75.2%) and DCR was 65% (95% CI 71.2%-91.9%) by RECIST v1.1. When evaluated by mRECIST, ORR and DCR improved to 24.2% (95% CI 55.8%-93.8%) and 75% (95% CI 74.2%-92.9%), respectively. Treatment-emergent adverse events (TEAEs) occurred in 75% of pts, 35% of which was ≥grade 3. Of which 31 patients (96.8%) were positive for CTC, ranging from 1 to 45, with a median of 7 (3, 11), 25 (78.1%) PD-L1+CTC was detected in 32 patients. The median follow-up time was 6 months (range, 2-14 months). Correlation analysis found that The 1-year progression-free survival rates of patients in the PD-L1+CTC group and those in the non-detected PD-L1+CTC group were 54.1% vs 28.6% respectively (P=0.036).

Conclusions

Tislelizumab combination with Sorafenib showed promising antitumor activity with relatively high ORR and a tolerable safety profile in 1st line HCC treatment. Baseline CTC PD-L1+ can be used as a predictive indicator for screening HCC patients for PD-1/PD-L1 blockade therapy, and dynamic measurement of CTC changes can monitor the therapeutic effect of patients.

Clinical trial identification

ChiCTR2100050076.

Editorial acknowledgement

Legal entity responsible for the study

Che Xu.

Funding

Sanming Project of Medicine in Shenzhen (No.SZSM202011010) and Shenzhen High-level Hospital Construction Fund.

Disclosure

All authors have declared no conflicts of interest.