958P - Preliminary results of radiotherapy (RT) combined with sintilimab (Sin) and bevacizumab (Bev) in advanced hepatocellular carcinoma (HCC) previously treated with immune checkpoint inhibitors (ICIs): A prospective phase II study

Background

ICIs have become the critical systematic drugs in advanced HCC, but most patients (pts) will be resistant to it. Evidence of the subsequent regimen for previously ICI-treated HCC pts is little. RT has shown synergistic effect with ICIs and may overcome ICIs resistance. Therefore, this study was designed to evaluate the efficacy and safety of RT combined with PD-1 inhibitor (Sin) and antiangiogenic drug (Bev) in advanced HCC pts who had previously received PD-(L)1 inhibitors.

Methods

This phase II trial study followed Simon’s two-stage design. A total of 21 HCC pts who had previously received ICIs will be enrolled. Pts will receive RT (30-40Gy/5-8F) combined with Sin(200mg iv. q3w) and Bev (15mg/kg iv. q3w). Sin and Bev will maintain until disease progression or intolerable toxicity, Sin up to 2 years. The primary endpoint was investigator evaluated objective response rate (ORR) per RECIST1.1. If more than 1 of 9 pts achieved objective response in stage I, the study will enter stage II.

Results

Between March 11, 2022 and April 15, 2023 (data cutoff), the median follow-up was 6.3 months (mo) (range: 2.3–13.2), 10 pts who previously received ICIs＋TKIs had been enrolled and received study therapy. 90% (9/10) were BCLC-C. 6 pts previously received one line therapy and 4 pts received two lines. 6 pts received last line immunotherapy less than 6 mo, and 4 pts ≥ 6 mo. All 10 pts received at least one radiological evaluation after baseline. 4 pts achieved partial response (PR) with an ORR of 40% (95% CI, 16.8%-68.7%) and a disease control rate (DCR) of 80% (95% CI, 49.0%-94.3%). Median progression-free survival (mPFS) was 7.4 mo (95% CI: 1.5–NA); Median overall survival (mOS) was not reached. Grade ≥ 3 treatment-related-adverse events (TRAEs) were reported in 3(30%) pts. Frequently occurring adverse events were grade 1-2, including abdominal distension (40%), hypertension (30%) and ALT, AST elevation (20%).

Conclusions

RT combined with Sin and Bev exhibited promising efficacy and favorable safety for HCC previously treated with ICIs. The trial is still recruiting, more data would be further analyzed and reported.

Clinical trial identification

ChiCTR2200056068.

Editorial acknowledgement

Legal entity responsible for the study

Union Hospital Tongji Medical College of Huazhong University of Science and Technology.

Funding

Innovent Biologics (Suzhou) Co. Ltd.

Disclosure

All authors have declared no conflicts of interest.