Combined immune checkpoint inhibition with durvalumab and tremelimumab with and without radiofrequency ablation in patients with advanced biliary tract carcinoma.

Abstract

e16158 Background: The prognosis of advanced bile tract cancer (BTC) is unfavorable with a 5-year overall survival (OS) rate of less than 10%. Durvalumab has been approved in the first line setting in combination with chemotherapy (gemcitabine with cisplatin) for advanced BTC. Monotherapy with immune checkpoint inhibitors (ICI) in BTC in the second line is suboptimal with ORR reported in the 5-15% range. The purpose of this study was to explore the efficacy of an anti-PD-L1 (durvalumab) agent in combination with an anti-CTLA4 (tremelimumab) agent with and without radio frequency ablations (RFA) in advanced BTC. Methods: Eligible patients with advanced BTC who had received or refused at least one prior line of systemic therapy were treated with tremelimumab 75 mg intravenously (IV) and durvalumab 1500 mg (IV) for 4 combined doses followed by monthly durvalumab 1500 mg IV alone until progression of disease or unacceptable toxicity. Objective response was assessed through CT or MRI by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) every 8 weeks. Adverse events (AEs) were recorded and managed. The primary endpoint was 6-month progression free survival (PFS). All patients underwent a pretreatment and on treatment biopsy. Results: 22 patients with advanced BTC were enrolled in this study; 10 patients were treated with durvalumab and tremelimumab (Durva/ Treme -Arm A) and 12 patients were treated with the combination of durvalumab and tremelimumab and an ablative procedure (Durva/ Treme/ RFA -Arm B). A total of 18 patients were evaluable (10 in Arm A and 8 in Arm B). The best clinical response in Arm A were as follows: PR (n=8), SD (n=1), PD (n=1) and in Arm B: SD (n=3), PD (n=5). The median progression free survival (PFS) in the Durva/ Treme Arm A was 3.3 months (95% CI: 1.9-3.9) and Durva/ Treme/ RFA Arm was 2 months (95% CI: 1.3-2.5)). The median overall survival (OS) in the Durva/ Treme Arm A was 6.1 months (95% CI: 3.5-7.4) and Durva/ Treme/ RFA Arm was 5.7 months (95% CI: 2.9-7.6). The most common study hematologic related Grade 3-4 adverse events (AEs) were lymphopenia (n=6) and anemia (n=3) and the most common non hematologic AEs included increased AST (n=9), increased alk phos (n=7) and increased total bilirubin (n=6). Conclusions: Combined ICI with Durva/ Treme with and without RFA is well tolerated; Durva/ Treme alone showed promising activity in this small early-stage study, with an ORR of 80%, in patients with advanced BTC. Clinical trial information: NCT02821754 .