Nivolumab Plus Ipilimumab Shows Encouraging Activity in Advanced Gallbladder Carcinoma

Results from the Phase 2 MoST-CIRCUIT Trial 

Clinical Summary: 

• Design/Population: The phase 2 MoST-CIRCUIT trial evaluated nivolumab plus ipilimumab in patients with advanced intrahepatic cholangiocarcinoma or gallbladder carcinoma who had received no more than 1 prior line of systemic therapy.
• Key Outcomes: Overall activity was modest, but patients with gallbladder carcinoma demonstrated higher response rates than those with intrahepatic cholangiocarcinoma, particularly among immunotherapy-naïve patients.
• Clinical Relevance: These findings suggest combined PD-1/CTLA-4 blockade may have greater clinical utility in gallbladder carcinoma than in other biliary tract cancers.

According to results from the phase 2 MoST-CIRCUIT trial, nivolumab plus ipilimumab demonstrated encouraging activity among patients with gallbladder carcinoma despite demonstrating limited overall efficacy among patients with advanced biliary tract cancers.

“Anti–PD-1/PD-L1 blockade combined with chemotherapy has become the first-line treatment for advanced biliary tract cancers,” stated Adnan Nagrial, MD, PhD, Blacktown and Westmead Hospitals, Sydney, Australia, and coauthors. “Combined anti–PD-1/CTLA-4 blockade using nivolumab and ipilimumab has shown encouraging activity in patients with intrahepatic cholangiocarcinoma and gallbladder carcinoma.”

In cohort B of this single-arm, non-randomized trial, researchers enrolled 60 patients with either intrahepatic cholangiocarcinoma (n = 37) or gallbladder carcinoma (n = 23) who had received ≤1 prior line of systemic therapy (n = 51), including durvalumab (n = 13). Patients received 3 mg/kg of nivolumab plus 1 mg/kg of ipilimumab once every 3 weeks for 4 doses followed by 480 mg of nivolumab every 4 weeks for 96 weeks, with response assessed every 12 weeks. Primary end points included objective response rate (ORR) and progression-free survival (PFS). Key secondary end points included median overall survival (OS), median PFS, and safety. 

At analysis, the ORR was 12%, including complete responses in 2% of patients and partial responses in 10% of patients. The 6-month PFS rate was 27%, and median OS was 7 months.

Responses were more frequent among patients with gallbladder carcinoma than those with intrahepatic cholangiocarcinoma, with ORRs of 26% and 3% and 6-month PFS rates of 39% and 19%, respectively. Among immunotherapy-naïve patients, the ORR was 19% overall, including 38% in patients with gallbladder carcinoma and 10% in patients with intrahepatic cholangiocarcinoma. 

Grade ≥3 immune-related adverse events occurred in 20% of patients.

“Efficacy was limited in what is the largest biliary tract cancer cohort treated to date with combined anti–CTLA-4/PD-1 blockade… [however] encouraging activity was observed in the [gallbladder cancer] subgroup,” concluded Dr Nagrial et al. “Further evaluation of checkpoint inhibition in biliary tract cancer should focus on patients with [gallbladder cancer].” 

Source: 

Nagrial A, Carlino MS, Gunjur A, et al. Nivolumab and ipilimumab combination treatment in patients with advanced intrahepatic cholangiocarcinoma and gallbladder cancer: Results from the phase II MoST-CIRCUIT trial. Clin Cancer Res. Published online: June 4, 2026. doi: 10.1158/1078-0432.CCR-25-4009