983P Camrelizumab (C) in combination with apatinib (A) in patients with advanced hepatocellular carcinoma (RESCUE): An open-label, multi-center, phase II trial

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. 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. 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: 983PEfficacy results in two cohortsFirst-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)NRNRmPFS, 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. Open table in a new tab *Independent central review. 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.