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)

Conditions

• Breast Adenocarcinoma
• Estrogen Receptor- Negative Breast Cancer
• Estrogen Receptor-positive Breast Cancer
• HER2/Neu Negative
• Invasive Breast Carcinoma
• Progesterone Receptor Negative
• Progesterone Receptor Positive Tumor
• Stage II Breast Cancer
• Stage IIA Breast Cancer
• Stage IIB Breast Cancer
• Stage IIIA Breast Cancer
• Stage IIIB Breast Cancer
• Triple-negative Breast Carcinoma

Interventions

DRUG

Doxorubicin

60 mg/m2 once every 2 weeks for 4 cycles.

DRUG

Cyclophosphamide

cyclophosphamide 600 mg/m2 (AC) once every 2 weeks for 4 cycles.

DRUG

Paclitaxel

Paclitaxel 80 mg/m2 IV once weekly for 12 weeks.

DRUG

Carboplatin

carboplatin IV 1.5 area under curve (AUC) once weekly for 12 weeks.

DRUG

Decitabine

Given IV

DRUG

Pembrolizumab

Given IV

Sponsors & Collaborators

• Merck Sharp & Dohme LLC

  collaborator INDUSTRY

• National Cancer Institute (NCI)

  collaborator NIH

• Virginia Commonwealth University

  lead OTHER

Principal Investigators

• Harry D. Bear, M.D., Ph.D. · Massey Cancer Center

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-01-24

Primary Completion

2022-08-04

Completion

2027-03-31

FDA Drug

Yes

Countries

• United States

Study Locations