FRIDAY, Nov. 22, 2024 (HealthDay News) -- Combination treatment with entinostat and nivolumab results in durable responses in a small subset of patients with advanced pancreatic ductal adenocarcinoma (PDA), according to a study published online Nov. 12 in Nature Communications.
Marina Baretti, M.D., from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore, and colleagues combined entinostat and nivolumab in patients with advanced PDA in a phase 2 study. A 14-day lead-in of entinostat 5 mg orally once weekly was followed by entinostat and nivolumab treatment.
Twenty-seven evaluable patients were enrolled between November 2017 and November 2020. The researchers found partial responses in three patients (objective response rate, 11 percent), with a median response duration of 10.2 months. Median progression-free survival was 1.89 months and overall survival was 2.729 months. Nineteen patients (63 percent) had grade ≥3 treatment-related adverse events, including reduced lymphocyte count, anemia, hypoalbuminemia, and hyponatremia. Entinostat yielded increases in dendritic cell activation and maturation. In a small subset of PDA patients, entinostat and nivolumab showed durable responses, although the primary end point was not met.
"This study creates a roadmap for this strategy, and future areas of exploration include additional mechanistic studies that will lead to combinatorial approaches, both preclinically and clinically, to expand the subset of patients that could benefit from an histone deacetylase inhibitor-based immunomodulatory strategy," the authors write.
Several authors disclosed ties to biopharmaceutical companies, including Syndax, which manufactures entinostat and supplied the study medications.
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