Neoadjuvant Pembrolizumab + Decitabine Followed by Std Neoadj Chemo for Locally Advanced HER2- Breast Ca

Summary

This study is a 2-cohort, open-label, multicenter, phase 2 study of a short course of immunotherapy consisting of sequential decitabine followed by pembrolizumab administered prior to a standard neoadjuvant chemotherapy regimen for patients with locally advanced HER2-negative breast cancer. The primary efficacy objective is to determine if the immunotherapy increases the presence and percentage of tumor and/or stromal area of infiltrating lymphocytes prior to initiation of standard neoadjuvant chemotherapy. At enrollment, patients will be assigned to one of 2 cohorts based on hormone receptor status. * Cohort A - patients with HER2-negative, hormone receptor-negative breast cancer (defined as both ER and PgR with \< 10% positive staining on IHC) Note: before beginning standard neoadjuvant chemotherapy, patients in Cohort A may be reassigned to Cohort A2 to receive extended pembrolizumab as part of new standard neoadjuvant and postoperative adjuvant therapy. * Cohort B - patients with HER2-negative, hormone receptor-positive breast cancer (defined as either ER or PgR with ≥ 10% positive staining on IHC)

Timeline

Start

2017-01-24

Primary completion

2022-08-04

Completion

2027-03-31

Publications

• Background Bear HD, Deng X, Bandyopadhyay D, Idowu M, Jenkins TM, Kmieciak M, Williams M, Archer G, Gwaltney L, Dillon P, Flora D, Stover D, Poklepovic AS, Hackney M, Ross M, Vachhani H, Louie R, McGuire KP, Grover A, Rahman T, Hendrix A. T-cell immune checkpoint inhibition plus hypomethylation for locally advanced HER2-negative breast cancer: a phase 2 neoadjuvant window trial of decitabine and pembrolizumab followed by standard neoadjuvant chemotherapy. J Immunother Cancer. 2025 Feb 27;13(2):e010294. doi: 10.1136/jitc-2024-010294.

Drugs

Indications