Phase I Study of Entinostat in Combination with Enzalutamide for Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer.

Entinostat at the selected dose levels in combination with a standard dose of enzalutamide showed a promising safety profile in this small phase I study BACKGROUND: Entinostat inhibits prostate cancer (PCa) growth and suppresses Treg cell function in vitro and in vivo.

This was a phase I study to explore the safety and preliminary efficacy of entinostat (3 and 5 mg orally per week) in combination with enzalutamide in castration-resistant PCa (CRPC). The study was carried out in an open-label two-cohort design. Patients who had developed disease progression on or were eligible for enzalutamide were enrolled in the study. The safety profile of the combination therapy, PSA levels, the pharmacokinetics of enzalutamide post-entinostat administration, peripheral T cell subtype (including Treg quantitation), and mononuclear cell (PBMC) histone H3 acetylation were analyzed.

Six patients with mCRPC were enrolled. There was no noticeable increment of fatigue related to entinostat. Toxicities possibly or probably related to entinostat or the combination therapy included G3 anemia 1/6 (17%), G2 WBC decrease 1/6 (17%), and other self-limiting grade 1 adverse events (AEs). Median duration of treatment with entinostat was 18 weeks. Entinostat did not affect the steady plasma concentration of enzalutamide. Increased PBMC histone H3 acetylation was observed in blood samples. No evident T cell subtype changes were detected, including in Treg quantitation.

Entinostat 5 mg weekly in combination with enzalutamide showed an acceptable safety profile in this small Phase I study. A planned Phase II part of the trial was terminated because of sponsor withdrawal.

The oncologist. 2021 Aug 24 [Epub ahead of print]

Jianqing Lin, Jacob Elkon, Brittany Ricart, Erica Palmer, Christian Zevallos-Delgado, Satish Noonepalle, Brooke Burgess, Robert Siegel, Yan Ma, Alejandro Villagra

Department of Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.

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