Phase III study of pembrolizumab (pembro) versus best supportive care (BSC) for second-line therapy in advanced hepatocellular carcinoma (aHCC): KEYNOTE-240 Asian subgroup.

526 Background: Pembro received accelerated approval for second-line therapy in aHCC based on KEYNOTE-224 (phase 2). KEYNOTE-240 (NCT02702401) is a randomized, phase 3 study of pembro v BSC in previously treated aHCC. We report outcomes for the Asian subgroup. Methods: Pts with a radiographic/pathologic HCC diagnosis, radiographic progression with/intolerance to sorafenib, Child-Pugh A disease, and ECOG PS 0/1 were randomized 2:1 to pembro (200 mg) + BSC or PBO + BSC Q3W (≤35 cycles or until confirmed PD/unacceptable toxicity). Pts were stratified by geographic region (Asia without Japan; non-Asia with Japan), AFP, and macrovascular invasion. Response was assessed Q6W (RECIST v1.1, central review). Primary end points: OS, PFS; secondary end points: ORR, DOR, safety. Data cutoff: Jan 2, 2019. Results: 413 pts were randomized (overall cohort: n = 278 pembro, n = 135 PBO; Asian subgroup [Hong Kong, Japan, Philippines, S Korea, Taiwan, Thailand]: n = 107, n = 50). HBV+ status and BCLC stage C were higher in Asian subgroup (HBV+: 51% v 24.5% overall; stage C: 86.6% v 79.4%). Median follow-up: pembro (21.3 mo overall; 23.5 mo); PBO (21.5 mo overall; 23.0 mo). Pembro improved OS v PBO (median OS [95% CI]: 13.9 [11.6-16.0] v 10.6 [8.3-13.5] mo; HR: 0.781; 95% CI, 0.611-0.998; P = 0.0238) and PFS (HR: 0.718; 0.570-0.904; P = 0.0022) for overall cohort and Asian subgroup (median OS: 13.8 [10.1-16.9] v 8.3 [6.3-11.8] mo; HR: 0.548; 0.374-0.804; P = 0.0009; PFS: HR: 0.475; 0.324-0.696; P < 0.0001). Differences did not meet prespecified significance level for overall cohort. ORR in overall cohort was 18.3% (14.0-23.4) for pembro; 4.4% (1.6-9.4; P = 0.00007) for PBO; in Asian subgroup, 20.6% (13.4-29.5) and 2.0% (0.1-10.6; P = 0.00135). Safety was consistent with that previously reported in pembro studies. No HBV/HCV flares were identified. Conclusions: Pembro reduced risk for death by 22% in overall cohort and 45% in Asian subgroup and improved PFS v PBO. Safety was comparable to that of pembro monotherapy. Results are consistent with KEYNOTE-224 and magnitude of OS benefit was enhanced in Asian subgroup, supporting a favorable risk-benefit balance for second-line pembro in HCC. Clinical trial information: NCT02702401.