Reversing Therapy Resistance With Epigenetic-Immune Modification

Summary

The investigators propose a randomized two arm trial, using Simon's 2-stage design, in ER+ patients with therapy resistant breast cancer to test the optimal sequence and dosing of epigenetic immune priming in hormone therapy resistance breast cancer. A third arm (Arm C) will include ER-negative patients who will follow the concurrent priming, but exclude tamoxifen. The two arms all include vorinostat, tamoxifen, and pembrolizumab to evaluate * Sequential priming - begin pembrolizumab in Cycle 1 (Arm B and Arm C) and, * Concurrent priming with maximal dosing of both epigenetic and immune modulators- begin pembrolizumab on day 1 in Cycle 2 (Arm A)

Timeline

Start

2015-05-04

Primary completion

2019-06-08

Completion

2019-06-08

Outcome

Outcome not reported

Stopped: “Insufficient efficacy in an unselected patient population”

Publications

• Terranova-Barberio M, Pawlowska N, Dhawan M, Moasser M, Chien AJ, Melisko ME, Rugo H, Rahimi R, Deal T, Daud A, Rosenblum MD, Thomas S, Munster PN. Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancer. Nat Commun. 2020 Jul 17;11(1):3584. doi: 10.1038/s41467-020-17414-y.

Drugs

Indications