SBRT with intratumoural pembrolizumab before neoadjuvant chemotherapy for high-risk 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

This study will test whether a short course of focused radiation plus two injections of pembrolizumab into the tumor before chemotherapy helps people with high‑risk invasive breast cancer respond better to treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's (Academic / other)
• Drugs / interventions: pembrolizumab, chemotherapy, radiation, immunotherapy
• Locations: 2 sites (London, Ontario and 1 other locations)
• Trial ID: NCT07188246 on ClinicalTrials.gov

What this trial studies

Participants receive stereotactic body radiation therapy (SBRT) to the primary breast tumor plus two intratumoural injections of pembrolizumab, followed by standard neoadjuvant chemotherapy. The trial aims to see if this combination increases immune activation in the tumor microenvironment and improves early clinical response. Key outcomes include feasibility, safety, molecular immune changes, and preliminary measures of tumor response before surgery. Results will inform whether a randomized trial of SBRT plus immunotherapy before chemotherapy is warranted.

Who should consider this trial

Good fit: Adults with palpable, high‑risk invasive breast carcinoma (stage IIB–III, or stage IIA if triple‑negative or HER2+) who plan to receive neoadjuvant chemotherapy and can tolerate biopsies and intratumoural injections are ideal candidates.

Not a fit: Patients with inflammatory breast cancer, prior treatment for the current breast cancer, prior radiation to the same breast, or serious comorbidities that prevent radiotherapy, chemotherapy, or surgery are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the regimen could increase the rate of complete tumor response to neoadjuvant chemotherapy and potentially improve long‑term outcomes.

How similar studies have performed: Prior feasibility trials (SIGNAL and TRIO) showed neoadjuvant SBRT can upregulate immune‑related genes and suggest improved responses, but adding intratumoural pembrolizumab is a novel extension being tested here.

Eligibility criteria

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.

Where this trial is running

London, Ontario and 1 other locations

• St. Joseph's Health Care London — London, Ontario, Canada (Not_yet_recruiting)
• St. Joseph's Health Care London — London, Ontario, Canada (Recruiting)

Study contacts

• Study coordinator: Muriel Brackstone, MD, PhD

Conditions Breast Cancer; Breast Cancer Stage II; Breast Cancer Stage III; Breast Cancer Invasive; Breast Cancer Triple Negative; Immunotherapy; Pembrolizumab; Breast SBRT