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

Not Applicable

Not yet recruiting

• Conditions: Breast Cancer; Breast Cancer Stage II; Breast Cancer Stage III; Breast Cancer Invasive; Breast Cancer Triple Negative
• Interventions: Radiation: Radiation; Drug: Pembrolizumab (KEYTRUDA®)

• Registration Number: NCT07188246
• Lead Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Brief 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.

Study Timeline

• Study First Submitted: 2023-05-04
• Status Verified: 2025-09
• Study First Submitted QC: 2025-09-20
• Last Update Submitted: 2025-09-20
• Study First Posted: 2025-09-23
• Last Update Posted: 2025-09-23
• Study Start: 2025-10-01
• Primary Completion: 2027-07
• Study Completion: 2029-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Invasive ductal carcinoma of any subtype (including invasive mammary carcinoma with lobular features), excluding sarcomatous, signet or metaplastic subtypes.

2. Invasive mammary carcinoma of stages IIB - III (excluding inflammatory breast cancer). Stage IIA is eligible for triple negative and HER2+ breast cancers.

   a. Clinical staging based on AJCC 8th edition.

3. Lesion palpable by treating physician.

4. Plan to be treated with neoadjuvant chemotherapy.

5. Able to tolerate core needle biopsies and pembrolizumab injection.

6. 18 years of age or older.

7. Able to provide informed consent.

Exclusion Criteria

1. Any serious medical comorbidities or other contraindications to radiotherapy, chemotherapy, or surgery (e.g., uncontrolled diabetes, serious heart condition, etc).
2. Prior treatment for current breast cancer.
3. Previous radiation therapy to the same breast.
4. Inflammatory breast carcinoma.
5. Invasive mammary carcinoma with sarcomatous, signet cell or metaplastic subtypes.
6. Recurrent breast cancer.
7. Clinical or radiologic evidence or suspicion of distant metastatic disease (metastatic workup that requires additional imaging to follow-up on suspicious findings will exclude patients).
8. Any collagen vascular disease precluding radiotherapy at the discretion of the treating radiation oncologist (particularly lupus, scleroderma, dermatomyositis, psoriatic arthritis).
9. No prior stem cell transplantation.
10. Any poorly controlled autoimmune conditions.
11. Current use of corticosteroids or immunosuppressants.
12. Any other malignancy at any site (except non-melanomatous skin cancer) <5 years prior to study enrollment. Synchronous bilateral breast cancers are acceptable.
13. Inability to tolerate core needle biopsies or pembrolizumab injection.
14. Pregnant or lactating.
15. Under 18 years of age.
16. Inability or unwillingness to provide informed consent.
17. Inability or unwillingness to complete study assessments/interventions and follow-up assessments.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SBRT with Pembrolizumab	Radiation	Stereotactic body radiation therapy delivered to the main breast tumour with 2 injections of pembrolizumab (Keytruda), completed prior to neoadjuvant chemotherapy.
SBRT with Pembrolizumab	Pembrolizumab (KEYTRUDA®)	Stereotactic body radiation therapy delivered to the main breast tumour with 2 injections of pembrolizumab (Keytruda), completed prior to neoadjuvant chemotherapy.

Primary Outcome Measures

Name	Time	Method
Pathological Complete Response	Measured at time of surgery, typically 6 months after enrollment in trial.	Pathologic complete response rates after neoadjuvant radiotherapy, pembrolizumab and chemotherapy will be evaluated.

Secondary Outcome Measures

Name	Time	Method
Immune priming	Measured 3 to 8 days after last dose of pembrolizumab. Which is Day 20-25, where blood and tissue will be collected.	To evaluate the degree of immune priming in this regimen compared descriptively to TRIO Trial
Breast and skin tissue adverse events to evaluate toxicity of treatment	Baseline, 3 weeks post-op, 6 months post-op, 1 year post-op	Toxicity to surrounding breast and skin tissue, defined by ≥ grade 2 fibrosis.
Treatment related adverse event	Measured at up to surgery, typically 6 months after enrolment in trial.	Adverse events relating to the interventional radiation or pembrolizumab defined by ≥ grade 3
Local Recurrence Rates	Disease status will be evaluated at routine patient follow-up appointments, including yearly mammography. Will be recorded at Year 1, Year 2, Year 3, Year 4, Year 5	Ipsilateral breast recurrence rate.

Trial Locations

Locations (2)

St. Joseph's Health Care London; 🇨🇦 London, Ontario, Canada

London Regional Cancer Program; 🇨🇦 London, Ontario, Canada