Microwave Ablation Plus Dual Checkpoint Inhibition Enhances Immune Response in Locally Advanced Pancreatic Ductal Adenocarcinoma
Key Clinical Takeaways
- Design/Population: In a single-arm study, 12 patients with unresectable, non-metastatic, locally advanced pancreatic ductal adenocarcinoma received combination therapy with durvalumab, tremelimumab, microwave ablation, and gemcitabine; 6 patients underwent single-cell transcriptomics and TCR profiling.
- Key Outcomes: Median PFS was 8.9 months overall and 11.2 months among patients completing therapy. One grade 5 toxicity occurred. Immune profiling showed overlap between CD8⁺ Temra cells in tumor and blood, and a high CD8⁺ Temra gene signature correlated with improved overall survival.
- Clinical Relevance: This combination regimen demonstrates early clinical activity and immune modulation. Findings suggest CD8⁺ Temra cells as potential biomarkers and therapeutic targets, supporting integration of local tumor ablation with immunotherapy in future clinical strategies.
According to results from an early phase 2 trial, combining dual immune checkpoint inhibitors durvalumab and tremelimumab with microwave tumor ablation and chemotherapy demonstrated encouraging progression-free survival (PFS) and potential immune modulation among patients with unresectable, non-metastatic, locally advanced pancreatic ductal adenocarcinoma.
“Despite significant advancements in cancer immunotherapy, survival outcomes remain poor in patients with pancreatic ductal adenocarcinoma,” stated Halit Topal, MD, University Hospitals KU Leuven, Leuven, Belgium, and coauthors. “This study aimed to explore whether combining immunotherapy with local tumor ablation and chemotherapy could improve outcomes for patients with advanced pancreatic cancer that cannot be surgically removed.”
In this open-label, single-arm study, 12 treatment-naïve patients with histologically proven unresectable non-metastatic locally advanced pancreatic ductal adenocarcinoma received durvalumab and tremelimumab with microwave ablation and gemcitabine. Single-cell transcriptomics and T cell receptor (TCR) profiling were used to characterize the tumor microenvironment (TME) and peripheral immune repertoire. Primary end points included PFS and safety. An exploratory end point was immune correlates of treatment response.
At analysis, median PFS was 8.9 months in the intention-to-treat population and 11.2 months in the 8 patients who completed combination therapy. Grade ≥3 treatment-related adverse events occurred in 3 patients, 2 of which were classified as serious. Single-cell and TCR profiling were performed in 6 patients, including 3 with paired pre- and post-treatment samples. Sample analysis revealed substantial overlap between T cell receptors and CD8⁺ Temra cells in both the TME and peripheral blood. Integration with an independent bulk transcriptomic dataset demonstrated that a high CD8⁺ Temra gene signature correlated with improved overall survival. However, TCR-related metrics did not reach statistical significance for association with PFS in this cohort.
Results demonstrate “that local tumor ablation may enhance tumor immunogenicity and systemic anti-tumor responses, supporting their integration into future treatment strategies,” concluded Dr Topal et al. “Future studies with larger cohorts are needed to validate these findings and optimize treatment protocols for wider clinical applicability.”
Source:
Topal H, Venken T, Bassez A, et al. Progression-free survival for unresectable non-metastatic locally advanced pancreatic cancer after surgical microwave ablation plus durvalumab and tremelimumab: phase-2 non-randomized prospective clinical trial. Commun Med. Published Online: November 18, 2025. doi:10.1038/s43856-025-01186-x
