Background: Tremelimumab is a fully human monoclonal antibody that binds to CTLA-4 expressed on the surface of activated T lymphocytes and results in inhibition of B7-CTLA-4-mediated downregulation of T-cell activation. Radiofrequency ablation (RFA) has been shown to induce a peripheral immune response which may enhance the effect of anti-CTLA4 treatment. Methods: Patients with refractory BTC were enrolled in a study of monthly Tremelimumab (10mg/kg, 6 doses) combined with RFA (to one lesion) performed on week 6. Tumor biopsies were performed at time of RFA with regular PBMC collection for intensive immunemontoring. Results: 17 pts enrolled. Characteristics: M:F 8:9; Median age 57(range 36-67); BTC subtype - intrahepatic/exrahepatic: 12/5. 13/17 had metastatic disease. All pts were chemorefractory with 12/17 having received at least 2 regimens. While on study, 6 pts had early PD within 6 weeks; 11 were able to undergo RFA. No DLT encountered. Most common toxicity was pruritus. There were no objective responses. Of evaluable pts N = 6 (55%) had stable disease as a best response. Conclusions: Tremelimumab in combination with subtotal RFA in patients with advanced BTC is safe and feasible. No objective responses have so far been seen in this predominantly primary intrahepatic BTC population. Full efficacy and immune monitoring data will be presented. Clinical trial information: NCT01853618