Background: Immune checkpoint blockade has improved outcomes in multiple tumor types, however little is known about the efficacy of these agents in rare tumors. We report the results of the gallbladder cohort of SWOG S1609 Dual Anti–CTLA-4 and anti–PD-1 blockade in Rare Tumors (DART). Methods: We performed a prospective, open label, multicenter phase II clinical trial of ipilimumab plus nivolumab across multiple rare tumor cohorts, with the gallbladder cohort reported here. Eligible patients had progressed following at least one line of standard systemic therapy, and did not have an approved or standard therapy available that had been shown to prolong survival. All participants received nivolumab 240 mg i.v. every 2 weeks and ipilimumab 1 mg/kg i.v. every 6 weeks on a continuous schedule. The primary endpoint was overall response rate [ORR; RECIST v1.1; complete response (CR) and partial response (PR)]; secondary endpoints included progression-free survival (PFS), overall survival (OS), stable disease >6 months, and toxicity Results: Nineteen patients (79% female) with a median age of 60 years were enrolled and received treatment. The median prior lines of therapy was 2 (range 1-6). The confirmed overall response rate was 16% [complete response, n=1 (5%); partial response, n=2 (11%)] (duration = 35+, 16, 13 mo). The unconfirmed overall response rate and clinical benefit rate were both 32% [complete response, n=1 (5%); partial response, n=5 (26%); stable disease > 6 months, n=0 (0%)]. The 6-month progression-free survival was 26% (95% CI 12-55%); median overall survival was 7.0 months (95% CI, 3.9-19.1 months). The most common toxicities were fatigue (32%), anemia (26%), and anorexia (26%). Aspartate aminotransferase elevation was the most common grade 3/4 toxicity (11%). There was one death from hepatic failure possibly related to treatment in the setting of progressive liver metastasis and biliary infection. Conclusions: Ipilimumab plus nivolumab demonstrated a 16% ORR in patients with gallbladder cancer including a complete response lasting 35+ months; The unconfirmed overall response rate was 32%. Clinical trial information: NCT02834013.

CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, overall response rate.