Multicenter phase 2 trial of nivolumab plus ipilimumab in advanced intrahepatic cholangiocarcinoma and gallbladder cancer

Anti-PD-(L)1 blockade combined with chemotherapy has become first-line treatment for advanced biliary tract cancer (BTC). Cohort B of the multicenter phase 2 MoST-CIRCUIT trial in Australia evaluated combined checkpoint blockade with nivolumab and ipilimumab in patients with advanced intrahepatic cholangiocarcinoma (iCCA) and gallbladder carcinoma (GBC). Patients with a maximum of one line of prior systemic therapy received four doses of nivolumab 3 mg/kg and ipilimumab 1 mg/kg every 3 weeks followed by nivolumab 480 mg every 4 weeks for 96 weeks. Co-primary endpoints were objective response rate (ORR) and 6-months progression-free survival rate (PFS-6). Sixty patients were enrolled (37 iCCA and 23 GBC) with 85% being pre-treated, including 13 with durvalumab. The ORR was 3% in the iCCA subgroup and 26% in the GBC subgroup; PFS-6 was 19% and 39%, respectively. In the immunotherapy-naïve population ORR was 10% in iCCA and 38% in GBC. Severe immune-related adverse events were observed in 20% of the patients. The authors conclude that efficacy of nivolumab plus ipilimumab was limited in BTC, but that encouraging activity was observed in the GBC subgroup.