NCT02957968

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

T-Cell Immune Checkpoint Inhibition Plus Hypomethylation for Locally Advanced HER2-Negative Breast Cancer - A Phase 2 Neoadjuvant Window Trial of Pembrolizumab and Decitabine Followed by Standard Neoadjuvant Chemotherapy

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 46 (actual)
• Sponsor: Virginia Commonwealth University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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)

Detailed description

Both cohorts will receive the identical doses and treatment schedules of decitabine and pembrolizumab followed by a standard neoadjuvant chemotherapy regimen. Both cohorts will receive 4 cycles of AC and 12 doses of weekly paclitaxel or Nab-paclitaxel. Paclitaxel or Nab-paclitaxel will be combined with carboplatin for Cohorts A and A2 (TNBC). The sequence of the 2 regimens will be at the discretion of the treating medical oncologist following the safety lead-in phase. For the primary endpoint, Cohorts A and A2 will be evaluated together, separate from Cohort B.

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

Type	Name	Description
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

Timeline

• Start date: 2017-01-24
• Primary completion: 2022-08-04
• Completion: 2026-03-31
• First posted: 2016-11-08
• Last updated: 2025-08-28
• Results posted: 2023-11-09

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study