O2-2-4 - Phase I study of nivolumab or nivolumab/cisplatin/gemcitabine to treat unresectable/recurrent biliary tract cancer.

This open-label study in Japan evaluated the safety and efficacy of an immune checkpoint inhibitor nivolumab (NIVO) alone or with gemcitabine-cisplatin (NIVO+GC) to treat biliary tract cancer (BTC). We present updated results for longer follow-up (minimum:493 days; median:679 days). Patients with unresectable/recurrent BTC refractory or intolerant to gemcitabine-based treatment received NIVO (240 mg, 2-week intervals, N = 30). Chemonaïve patients with unresectable/recurrent BTC received the same NIVO regimen + GC (N = 30). Primary objectives were tolerability and safety. Overall survival (OS) and centrally assessed progression-free survival (PFS) and objective response rate (ORR) were secondary efficacy endpoints. The most frequent drug-related adverse events with NIVO were decreased appetite (5/30, 17%), malaise (4/30, 13%), and pruritus (4/30, 13%), and with NIVO+GC w ere platelet count decreased (25/30, 83%) and neutrophil count decreased (25/30, 83%). In the NIVO cohort, median OS was 5.7 months (mo) (95% CI: 4.5, 8.7), median PFS was 1.4 mo (1.4, 1.4) and ORR was 10% (4, 23). Median OS was longer, and ORR higher, in the subgroup with programmed death-ligand 1 (PD-L1) ≥1% in tumor-associated immune cells (TAIC) (n = 19) than in those with PD-L1 <1% (n = 10) (OS:8.3 mo [4.8, 9.4] vs 4.3 mo [3.1, 6.4]; ORR:16% [7, 34] vs 0% [0, 21]). In the NIVO+GC cohort, median OS was 13.8 mo (95% CI:12.2, 15.9), median PFS was 4.3 mo (4.0, 7.9), and ORR was 37% (24, 52). Median OS was longer, and ORR higher, in patients with PD-L1 ≥1% (n = 18) than in those with PD-L1 <1% (n = 10) (OS:15.0 mo [12.2, 17.5] vs 13.0 mo [5.7, 15.4]; ORR:44% [27, 63] vs 20% [7, 46]). Median PFS was similar in the PD-L1 subgroups for both cohorts. Longer follow-up of patients with unresectable/recurrent BTC confirmed NIVO was well tolerated, with a manageable safety profile. Further data may show an association between PD-L1 expression in TAIC and longer OS with NIVO. [ABSTRACT FROM AUTHOR]