Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Results from CheckMate 040.

4012 Background: NIVO monotherapy (mono) is approved for sorafenib (SOR)-treated pts with HCC based on data from CheckMate 040 (NCT01658878), which reported an objective response rate (ORR) of 14% and median overall survival (mOS) of 16 months (mo). This is the first report of efficacy and safety of the NIVO + IPI combination in SOR-treated pts with aHCC. Methods: Pts were randomized to 3 arms: [A] NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses) or [B] NIVO 3 mg/kg + IPI 1 mg/kg Q3W (4 doses), each followed by NIVO 240 mg Q2W, or [C] NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W. Treatment continued until intolerable toxicity or disease progression. Primary endpoints included safety and tolerability. Secondary endpoints included ORR (BICR per RECIST v1.1), duration of response (DOR), disease control rate (DCR), and OS. Cutoff was 25 Sep 2018. Results: 148 SOR-treated pts were randomized. Minimum follow-up for OS from last pt randomization date to data cutoff was 24 mo. At baseline: 88% had vascular invasion or extrahepatic spread, 91% had BCLC stage C, 84% discontinued SOR due to disease progression and 14% due to toxicity. Overall, ORR was 31% (7 had a complete response [CR]) with a median DOR of 17 mo; DCR was 49% and 24-mo OS rate was 40%. Pts in arm A had a mOS of 23 mo and 4 pts had a CR. The table shows additional efficacy results by arm. Overall, NIVO + IPI was well tolerated; 37% of pts had a grade 3–4 treatment-related adverse event (TRAE; most common: pruritus and rash); 5% had grade 3–4 TRAEs leading to discontinuation. Conclusions: NIVO + IPI led to clinically meaningful responses and had an acceptable safety profile in SOR-treated pts, with an ORR twice that of NIVO mono (31% and 14%, respectively). Pts in arm A had the most promising mOS of 23 mo. Clinical trial information: NCT01658878. [Table: see text]