NCT07188246

Neoadjuvant, SBRT With Intratumoural Pembrolizumab Followed by Neoadjuvant Chemotherapy in Breast Cancer

A Trial of Neoadjuvant, Hypofractionated Radiation, With Intratumoural Pembrolizumab Followed by Neoadjuvant Chemotherapy, in Stage 3 or High-risk Stage 2 Breast Cancer

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will evaluate the immune-priming effects of stereotactic body radiation therapy (SBRT) regimen coupled with two injections of pembrolizumab in high-risk primary breast carcinoma prior to neoadjuvant chemotherapy. Preliminary results from the investigators' local TRIO Trial suggest that SBRT prior to neoadjuvant chemotherapy (NAC) may result in improved response rates due to the combined effect of radiation therapy (RT) and chemotherapy. The investigators aim to augment this effect with the addition of pembrolizumab, a monoclonal antibody that binds to and blocks programmed cell death protein 1 (PD-1).

Detailed description

This study will evaluate the immune-priming effects of stereotactic body radiation therapy (SBRT) combined with intratumoural pembrolizumab in patients with high-risk primary breast carcinoma prior to neoadjuvant chemotherapy. Prior feasibility trials (SIGNAL and TRIO) demonstrated that neoadjuvant SBRT can upregulate immune-related genes, suggesting conversion of tumors toward an "immune hot" phenotype that may enhance responsiveness to immunotherapy. The current trial builds on this work by adding pembrolizumab, an anti-PD-1 antibody, to determine whether further immune priming can be achieved. Study objectives include assessing feasibility, safety, molecular immune activation, and preliminary clinical outcomes of this regimen before standard chemotherapy. SBRT is a highly targeted radiotherapy technique that has demonstrated feasibility in early and locally advanced breast cancer trials, with low toxicity. Pembrolizumab is approved for multiple cancers, including triple negative breast cancer, and may act synergistically with radiotherapy to enhance antitumor immune responses. Findings from this study will inform future randomized trials evaluating whether combining SBRT and immunotherapy can improve pathologic complete response rates and long-term outcomes in breast cancer.

Conditions

• Breast Cancer
• Breast Cancer Stage II
• Breast Cancer Stage III
• Breast Cancer Invasive
• Breast Cancer Triple Negative

Interventions

Type	Name	Description
RADIATION	Radiation	Stereotactic body radiation therapy to the breast
DRUG	Pembrolizumab (KEYTRUDA®)	Two injections

Timeline

• Start date: 2026-01-19
• Primary completion: 2027-07-01
• Completion: 2029-02-01
• First posted: 2025-09-23
• Last updated: 2026-02-11

Locations

2 sites across 1 country: Canada