Preoperative Chemotherapy, Pembrolizumab and Low or High Dose RADiation in an Expansion Cohort of Node(+), Triple Negative Breast Cancer

NCT07276880 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: LCCC2426-DCTR01CA274254
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective radiation dose-finding, phase 2 expansion study of the Triple Negative (TN) cohort of the multicenter randomized study P-RAD (A Randomized Study of Preoperative Chemotherapy, Pembrolizumab and No, Low or High Dose RADiation in Node-Positive, HER2-Negative Breast Cancer; NCT04443348) that seeks to establish the optimal dose of radiation therapy (RT) to elicit an immune response when combined with immune checkpoint inhibitor (ICI) in breast cancer patients. Eligible subjects include women or men with operable, lymph node-positive, triple negative (TN) breast cancer who are candidates for standard of care neoadjuvant chemo-immunotherapy (NAC) based on the KEYNOTE-522 clinical trial. Thirty-two (n=32) patients will be randomized 1:1 to receive either low RT boost (9Gy total) or high RT boost (24Gy total). All RT will be delivered to the intact breast tumor in 3 daily fractions over 3 days. In the Neoadjuvant Phase, the first cycle (C1) of pembrolizumab (200 mg i.v.) will be administered within 0-2 days of initiating RT. Participation in this study requires availability of residual diagnostic tissue biopsies of the primary tumor and metastatic lymph node for research use. If this tissue is not available, baseline research biopsies will be performed. Additionally, a research biopsy of the breast tumor and lymph node is required on Day 10-14 of C1 of pembrolizumab. After completion of the research biopsy in Week 2, the participants can commence standard-of-care neoadjuvant chemotherapy and pembrolizumab at the discretion of their medical oncology provider. After completing NAC, participants will undergo standard of care surgical resection of the breast and axillary lymph nodes, at the discretion of their surgical oncology provider. In the Adjuvant Phase, participants will receive standard of care adjuvant systemic therapy and standard of care adjuvant radiotherapy (if indicated), although recognizing that the breast tumor boost portion of this treatment has already been administered preoperatively. Except for late radiation adverse reactions of special interest, which will be followed yearly for up to 5 years, follow-up will occur every 6 months for 3 years.

Conditions

HER2-Negative Breast Carcinoma; Node-positive Breast Cancer; Breast Cancer; Triple Negative Breast Cancer (TNBC)

Keywords

radiation therapy; neoadjuvant treatment; pembrolizumab; immune checkpoint inhibitor; radiotherapy boost

Outcome Measures

Primary Outcomes (1)

• Nodal Pathologic Complete Response rate(pCR)

  Nodal pCR is defined in a patient with no residual cancer cells in all sampled regional lymph nodes following completion of neoadjuvant systemic therapy as assessed by the study pathologist at the time of definitive surgery. Nodal pCR rates will be calculated and analyzed separately for patients receiving low versus high dose RT. A pooled analysis, incorporating the corresponding (3Gyx3 or 8Gyx3) patient cohort from the P-RAD trial, will be performed.

  Time of surgery (24 week)

Secondary Outcomes (17)

• The CD3+/CD8+ T cell Breast post-treatment biopsy

  Time of surgery (24 week)

• Composite pathologic complete response (pCR) (ypT0/Tis ypN0)

  Time of surgery (24 week)

• Total residual cancer burden (RCB)

  Time of surgery (24 week)

• Nodal pathologic complete response (pCR)

  Time of surgery (24 week)

• Composite pathologic complete response (pCR)

  Time of surgery (24 week)

Study Arms (2)

ARM 1

EXPERIMENTAL

Participants will receive a low dose radiation therapy boost in 3 fractions (3Gy x 3 fraction = 9Gy total).

Drug: Neoadjuvant Pembrolizumab; Radiation: low dose neoadjuvant boost

ARM 2

EXPERIMENTAL

Participants will receive a high dose radiation therapy boost in 3 fractions (8Gy x 3 fraction = 24Gy total).

Drug: Neoadjuvant Pembrolizumab; Radiation: High dose neoadjuvant boost

Interventions

High dose neoadjuvant boost RADIATION

An external beam radiotherapy boost of 24Gy total will be administered over 3 fractions.

ARM 2

Neoadjuvant Pembrolizumab DRUG

200 milligrams per square meter Neoadjuvant Pembrolizumab will be administered intravenously.

ARM 1; ARM 2

low dose neoadjuvant boost RADIATION

An external beam radiotherapy boost of 9Gy total will be administered over 3 fractions.

ARM 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to participate in this study, a subject must meet all of the eligibility criteria outlined below.
• Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information. Subjects are willing and able
• to comply with study procedures based on the judgment of the investigator.
• Age ≥ 18 years at the time of consent.
• ECOG or Karnofsky Performance Status of 0 or 1

You may not qualify if:

• Active infection requiring systemic therapy.
• Pregnant or breastfeeding.
• Prior ipsilateral invasive breast, chest wall or thoracic radiotherapy
• Prior ipsilateral invasive breast cancer, contralateral breast cancer or a known
• additional, invasive malignancy that is progressing or required active treatment in
• the last 5 years

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Related Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Dana Casey, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Taylor Pierce

CONTACT

919-984-0000; Taylor_Pierce@med.unc.edu

Emily L Schworer

CONTACT

919-984-0000; emily_lane@med.unc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: hybrid decentralized

Study Record Dates

• First Submitted: December 1, 2025
• First Posted: December 11, 2025
• Study Start: March 17, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): January 1, 2032
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)