Dr Baretti on Entinostat Plus Nivolumab in Advanced PDAC

Marina Baretti, MD, assistant professor, Johns Hopkins School of Medicine, discusses results and from a single-center, open-label, phase 2 trial (NCT03250273) evaluating entinostat in combination with nivolumab (Opdivo) for the treatment of patients with advanced pancreatic ductal adenocarcinoma (PDAC).

The study aimed to address the immune-suppressive nature of the tumor microenvironment (TME) in PDAC, which poses challenges for immune checkpoint inhibitor therapy in this patient population. Patients received 5 mg of oral entinostat once per week during a 14-day lead-in period, followed by 5 mg of entinostat in combination with 240 mg of nivolumab once every 2 weeks.

Results presented at the 2024 AACR Annual Meeting showed that patients with advanced PDAC treated with the combination (n = 27) experienced an overall response rate (ORR) per RECIST v1.1 criteria of 11% (95% CI, 2.4%-29.2%) and a disease control rate of 18.5% (95% CI, 6.3%-38.1%). The median duration of response was 10.2 months. The most common any-grade treatment-related adverse effects (TRAEs) in the safety population (n = 30) included fatigue (67%), anorexia (50%), nausea (33%), anemia (30%, decreased lymphocyte count (27%), vomiting (20%), and hyponatremia (17%).

Based on the ORR observed during the study, investigators plan to revisit preclinical models to explore different timing and dosing of entinostat, Baretti says. Other types of combinations utilizing entinostat could also be explored, as researchers look to answer other questions regarding how the agent could modulate the TME in PDAC, she expands. She notes that reprogramming of dendritic cells has been observed with entinostat. Therefore, combining the agent with other drugs that more heavily rely on the function of dendritic cells could be another possible avenue of investigation, she concludes.