Abstract 983P
Background
Combination of checkpoint inhibitors (CPIs) with anti-angiogenic agents are emerging as potential novel treatment options of hepatocellular carcinoma (HCC). Here we assessed the efficacy and safety of C+A in patients (pts) with advanced HCC.
Methods
This phase II study was conducted at 25 study sites in China. Pts with advanced HCC, treatment-naive or failure to sorafenib or donafenib were enrolled. Pts received intravenous C 200 mg every 2 weeks plus A 250 mg qd. The primary endpoint was objective response assessed by independent central review per RECIST v1.1.
Results
From Mar 2018 to Jan 2019, 70 pts in first-line setting and 120 pts in second-line setting were enrolled and received treatment of C+A. 168 (88%) of 190 pts were with HBV infection. As of Jan, 2020, median follow-up was 16.7 months and 14.0 months in the first-line and second-line treatment cohort, respectively. The objective response rate (ORR) assessed by independent central review per RECIST v1.1 was 34% and 23%; ORR assessed by independent central review per mRECIST was 46% and 25%; the 12-month overall survival (OS) rate was 75% and 68%, respectively. As of Apr 2020, the 18-month OS rate was 58% in the first-line cohort (table). Overall, 147 (77%) pts had grade ≥3 treatment-related AEs, with the most common being hypertension (34%), and increased γ-GT (12%). Twenty-three (12%) pts discontinued the treatment of either drug due to a treatment-related AE. Table: 983P
Efficacy results in two cohorts
| First-line cohort (N = 70) | Second-line cohort (N = 120) | |||
| RECIST v1.1* | mRECIST* | RECIST v1.1* | mRECIST* | |
| ORR, % (95% CI) | 34 (23, 47) | 46 (34, 58) | 23 (15, 31) | 25 (18, 34) |
| DCR, % (95% CI) | 77 (66, 86) | 79 (67, 88) | 76 (67, 83) | 76 (67, 83) |
| mDoR, months (95% CI) | 14.8 (5.5, NR) | NR (5.8, NR) | NR | NR |
| mPFS, months (95% CI) | 5.7 (5.4, 7.4) | 6.4 (4.8, 9.2) | 5.5 (3.7, 5.6) | 5.5 (3.7, 7.3) |
| 12-month OS, % (95% CI) | 75 (63, 84) | 68 (59, 76) | ||
| 18-month OS, % (95% CI) | 58 (46, 69) | NE |
*Independent central review.
Conclusions
C+A provided high ORR, durable response with a manageable safety profile in advanced HCC pts. Notably, the remarkable survival benefit might suggest C+A is a promising strategy in advanced HCC pts.
Clinical trial identification
NCT03463876.
Editorial acknowledgement
Legal entity responsible for the study
Jiangsu Hengrui Medicine Co., Ltd.
Funding
Jiangsu Hengrui Medicine Co., Ltd.
Disclosure
Q. Wang: Full/Part-time employment: Jiangsu Hengrui Medicine Co., Ltd. All other authors have declared no conflicts of interest.