Pembrolizumab and Tamoxifen With or Without Vorinostat for the Treatment of Estrogen Receptor Positive Breast Cancer

Summary

Participation Requirements

Description

PRIMARY OBJECTIVE: I. To define the role of epigenetic immune priming in a biomarker enriched estrogen receptor (ER)+ breast cancer population on the basis of overall response rate. SECONDARY OBJECTIVES: I. To assess duration of response (DOR) 24-week landmark progression-free survival (PFS:24). II....

PRIMARY OBJECTIVE: I. To define the role of epigenetic immune priming in a biomarker enriched estrogen receptor (ER)+ breast cancer population on the basis of overall response rate. SECONDARY OBJECTIVES: I. To assess duration of response (DOR) 24-week landmark progression-free survival (PFS:24). II. Median PFS and overall survival (OS). III. Tumor responses will also be calculated by Immune Related Response-Criteria (irRC). EXPLORATORY OBJECTIVES: I. Evaluation of biomarker target threshold on response rate (retrospective cut off of 20% versus [vs] 10%). II. To assess the ratio of effector T cells: regulatory T cells in blood and tumor biopsies pre- and post-therapy. III. To evaluate inflammatory T cell signature changes in blood and tumor biopsies pre- and post-therapy. IV. To evaluate changes in number of myeloid-derived suppressor cells (MDSCs) in peripheral blood and tumor biopsies pre- and posttherapy. V. To evaluate changes in histone acetylation in peripheral blood cells and tumor biopsies pre- and post-therapy. VI. Initial comparison to vorinostat-induced PD-1 in lymphocytes, PD-L1 modulation. VII. Nanostring and 10 x sequencing and single cell immune phenotyping (on stored tissue for successful arms only). VIII. Impact of histone deacetylase (HDAC) inhibition of response to pembrolizumab vs. pembrolizumab in biomarker enriched population. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1, vorinostat orally (PO) once daily (QD) for 4 days weekly, and tamoxifen PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression of unacceptable toxicity. ARM B: Patients receive pembrolizumab IV over 30 minutes on day 1 and tamoxifen PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression of unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days and then every 12 weeks thereafter.

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