Tremelimumab in combination with microwave ablation in patients with refractory biliary tract cancer

Abstract

Background and Aim

Treatment options for patients with advanced biliary tract cancer are limited. Dysregulation of the immune system plays an important role in the pathogenesis of biliary tract cancer (BTC). This study aimed to investigate whether tremelimumab, an anti‐CTLA4 inhibitor, could be combined safely with microwave ablation to enhance the effect of anti‐CTLA4 treatment in patients with advanced BTC. Patients were enrolled to receive monthly tremelimumab (10mg/kg, intravenously) for 6 doses, followed by infusions every 3 months until off‐treatment criteria were met. Thirty‐six days after the first tremelimumab dose, patients underwent subtotal microwave ablation. Interval imaging studies were performed every 8 weeks. Adverse events were noted and managed. Tumor and peripheral blood samples were collected to perform immune monitoring and whole exome sequencing.

Results

Twenty patients with refractory BTC were enrolled. Median age 56.5 years. No dose‐limiting toxicities were encountered. The common treatment related adverse events included lymphopenia, diarrhea and elevated transaminases. Among sixteen patients evaluable for efficacy analysis, two (12.5%) patients achieved a confirmed partial response (lasting for 8.0 and 18.1 months, respectively), 5 patients (31.3%) achieved stable disease. Median progression free survival, and overall survival were 3.4 months (95% CI 2.5‐5.2 months), and 6.0 months (95% CI 3.8‐8.8 months), respectively. Peripheral blood immune cell subset profiling showed increased circulating activated (HLA‐DR positive) CD8+ T cells. TCRβ screening showed tremelimumab expanded TCR repertoire but not reaching statistical significance (P=0.057).

Conclusions

Tremelimumab in combination with tumor ablation is a potential new treatment strategy for patients with advanced BTC. Increased circulating activated CD8+ T cells and TCR repertoire expansion induced by tremelimumab may contribute to treatment benefit.

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