Nivolumab and Ipilimumab Combination Treatment in Patients with Advanced Intrahepatic Cholangiocarcinoma and Gallbladder Cancer: Results from the Phase II MoST-CIRCUIT Trial

Nagrial, A; Carlino, MS; Gunjur, A; Brown, MP; Harris, S; Underhill, C; Zielinski, R; Kee, D; Lam, WS; Chan, H; Harrup, R; So, J; Collins, IM; Michael, M; Chionh, F; Uy, C; Mariadason, J; Torres, J; Ballinger, ML; Grady, JP; Tavancheh, E; Palmer, J; Thomas, DM; Wilkie, K; Cebon, J; Klein, O

Author(s): Nagrial, A; Carlino, MS; Gunjur, A; Brown, MP; Harris, S; Underhill, C; Zielinski, R; Kee, D; Lam, WS; Chan, H; Harrup, R; So, J; Collins, IM; Michael, M; Chionh, F; Uy, C; Mariadason, J; Torres, J; Ballinger, ML; Grady, JP; Tavancheh, E; Palmer, J; Thomas, DM; Wilkie, K; Cebon, J; Klein, O;
Details: Publication Year 2026-08-03,Volume 32,Issue #15,Page 3203-3212
Journal Title: Clinical Cancer Research
Publication Type: Research article
Abstract: PURPOSE: Anti-PD-1/PD-L1 blockade combined with chemotherapy has become the first-line treatment for advanced biliary tract cancers. Combined anti-PD-1/CTLA-4 blockade using nivolumab and ipilimumab has shown encouraging activity in patients with intrahepatic cholangiocarcinoma (iCCA) and gallbladder carcinoma (GBC) in two trials (CA209-538 and SWOG1609). MoST-CIRCUIT further evaluated combined checkpoint blockade using nivolumab/ipilimumab in patients with advanced iCCA and GBC. PATIENTS AND METHODS: Patients with a maximum of 1 line of prior systemic therapy were enrolled as cohort B into MoST-CIRCUIT, a single-arm, nonrandomized phase 2 trial. Patients received nivolumab 3 mg/kg and ipilimumab 1 mg/kg every 3 weeks for four doses, followed by nivolumab 480 mg every 4 weeks for 96 weeks. Response (RECIST 1.1) was assessed every 12 weeks. Coprimary endpoints were objective response rate (ORR) and 6-month progression-free survival (6-PFS), with the secondary endpoints being median overall survival (mOS), PFS, and treatment-related toxicity. RESULTS: Sixty patients (37 iCCA and 23 GBC) were enrolled; 85% were pretreated, including 13 patients with durvalumab. The ORR was 12% (2% complete response, 10% partial response): 3% and 26% in the iCCA and GBC subgroups, respectively. The 6-PFS was 27% (iCCA 19%; GBC 39%), and mOS was 7 months. In the immunotherapy-naïve population, the ORR was 19% (iCCA 10%; GBC 38%). Severe immune-related adverse events were observed in 20% of patients. CONCLUSIONS: Efficacy was limited in what is the largest biliary tract cancer cohort treated to date with combined anti-CTLA-4/PD-1 blockade. Encouraging activity was observed in the GBC subgroup. Further evaluation of checkpoint inhibition in biliary tract cancer should focus on patients with GBC.
Publisher: American Association for Cancer Research
Keywords: Humans; Female; *Cholangiocarcinoma/drug therapy/pathology/mortality; Ipilimumab/administration & dosage/adverse effects; *Gallbladder Neoplasms/drug therapy/pathology/mortality; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse; effects/administration & dosage; Aged; Middle Aged; Nivolumab/administration & dosage/adverse effects; Male; *Bile Duct Neoplasms/drug therapy/pathology/mortality; Adult; Aged, 80 and over
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1158/1078-0432.Ccr-25-4009
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-05-19 06:10:13

Last Modified: 2026-09-14 12:01:09