Entinostat May Improve Benefit of High-dose IL-2 in RCC

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Entinostat may synergistically improve the therapeutic effect of high dose interleukin-2 in treatment-naïve clear cell renal cell carcinoma.
Entinostat may synergistically improve the therapeutic effect of high dose interleukin-2 in treatment-naïve clear cell renal cell carcinoma.

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.

RELATED: Circulating FGF21 Found To Be a Diagnostic, Prognostic Marker in RCC

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.

Reference

  1. 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.

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