Open AccessPhase I Study of Entinostat in Combination with Enzalutamide for Treatment of Patients with Metastatic Castration‐Resistant Prostate Cancer
Author(s) -
Lin Jianqing,
Elkon Jacob,
Ricart Brittany,
Palmer Erica,
ZevallosDelgado Christian,
Noonepalle Satish,
Burgess Brooke,
Siegel Robert,
Ma Yan,
Villagra Alejandro
Publication year - 2021
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1002/onco.13957
Subject(s) - enzalutamide , medicine , prostate cancer , peripheral blood mononuclear cell , oncology , combination therapy , cancer , pharmacology , androgen receptor , in vitro , biochemistry , chemistry
Lessons Learned Entinostat at the selected dose levels in combination with a standard dose of enzalutamide showed a promising safety profile in this small phase I studyBackground Entinostat inhibits prostate cancer (PCa) growth and suppresses Treg cell function in vitro and in vivo. Methods 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, Prostate specific antigen (PSA) levels, the pharmacokinetics of enzalutamide after entinostat administration, peripheral T‐cell subtype (including Treg quantitation), and mononuclear cell (PBMC) histone H3 acetylation were analyzed. Results Six patients with metastatic CRPC were enrolled. There was no noticeable increment of fatigue related to entinostat. Toxicities possibly or probably related to entinostat or the combination therapy included grade 3 anemia 1/6 (17%), grade 2 white blood cell (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. Conclusion 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.