Entinostat, a class 1 selective histone deacetylase (HDAC) inhibitor, may synergistically improve the therapeutic effect of high dose interleukin-2 (IL-2) in treatment-naïve patients with clear cell renal cell carcinoma (RCC).1
Previous research has demonstrated that entinostat increases the antitumor effects of high-dose IL-2 in preclinical models of RCC by down-regulating Foxp3 expression and function of regulatory T cells. Therefore, researchers sought to evaluate entinostat plus high-dose IL-2 in patients with metastatic clear cell RCC.
For the phase 1/2 study, researchers enrolled 47 patients with clear cell RCC who had received no prior treatments and were going to receive high-dose IL-2. In the phase 1 portion, patients received entinostat 3 or 5 mg orally every 14 days plus IL-2 600 000 units/kg intravenously every 8 hours for up to 14 doses during each 85-day cycle.
The results, which were presented at the American Academy for Cancer Research (AACR) Annual Meeting 2016, showed that no patients experienced dose-limiting toxicities and the 5-mg dose of entinostat was recommended for phase 2.
Researchers found that the objective response rate was 35%, which included 3 complete responses and 10 partial responses. Median progression-free survival was 16.1 months (95% CI, 6.2 – 27.8) and median overall survival was 65.3 months.
The study further demonstrated that decreased levels of regulatory T cells following treatment were associated with response.
The findings ultimately suggest that entinostat represents the first example of how an epigenetic agent can be rationally combined with immunotherapies.
- Pili R, Quinn DI, Hammers HJ, et al. Results from a phase I/II study with the HDAC inhibitor entinostat in combination with high-dose interleukin-2 in renal cell carcinoma patients (CTEP#7870). Oral presentation at: AACR Annual Meeting 2016; April 16-20, 2016; New Orleans, LA.