A Phase 2 trial tested the combination of Azacitidine and Pembrolizumab as a second-line treatment for advanced pancreatic ductal adenocarcinoma. The goal was to “prime” the tumor with Azacitidine to make it more visible to the immune system and improve response to immunotherapy.
The study enrolled 36 patients, with 31 evaluable for efficacy. Results showed limited activity: only 9.7% achieved a partial response, and the disease control rate was 35.5%. Median progression-free survival was 1.51 months, and overall survival was 4.83 months. Side effects were generally manageable, though one patient died from immune-related encephalitis.
Biomarker analysis suggested that pre-existing immune activity predicted better outcomes. Patients with higher CD8+ T-cell levels, lower tumor proliferation (Ki-67), or rare mutations like POLE and BRCA1 responded better. PD-L1 expression did not predict benefit.
Researchers concluded that this combination should not move forward in unselected PDAC patients. Future studies may focus on biomarker-driven approaches or more complex combinations to overcome the strong immune resistance of pancreatic cancer.