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

NCT07188246 | Recruiting Phase 2 DMC

• 1 other identifier: 122109
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

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).

Conditions

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

Keywords

Immunotherapy; Pembrolizumab; Breast SBRT

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response

  Pathologic complete response rates after neoadjuvant radiotherapy, pembrolizumab and chemotherapy will be evaluated.

  Measured at time of surgery, typically 6 months after enrollment in trial.

Secondary Outcomes (4)

• Immune priming

  Measured 3 to 8 days after last dose of pembrolizumab. Which is Day 20-25, where blood and tissue will be collected.

• Breast and skin tissue adverse events to evaluate toxicity of treatment

  Baseline, 3 weeks post-op, 6 months post-op, 1 year post-op

• Treatment related adverse event

  Measured at up to surgery, typically 6 months after enrolment in trial.

• 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

Study Arms (1)

SBRT with Pembrolizumab

EXPERIMENTAL

Stereotactic body radiation therapy delivered to the main breast tumour with 2 injections of pembrolizumab (Keytruda), completed prior to neoadjuvant chemotherapy.

Radiation: Radiation; Drug: Pembrolizumab (KEYTRUDA®)

Interventions

Radiation RADIATION

Stereotactic body radiation therapy to the breast

SBRT with Pembrolizumab

Pembrolizumab (KEYTRUDA®) DRUG

Two injections

SBRT with Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Invasive ductal carcinoma of any subtype (including invasive mammary carcinoma with lobular features), excluding sarcomatous, signet or metaplastic subtypes.
• 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.
• Lesion palpable by treating physician.
• Plan to be treated with neoadjuvant chemotherapy.
• Able to tolerate core needle biopsies and pembrolizumab injection.
• years of age or older.
• Able to provide informed consent.

You may not qualify if:

• Any serious medical comorbidities or other contraindications to radiotherapy, chemotherapy, or surgery (e.g., uncontrolled diabetes, serious heart condition, etc).
• Prior treatment for current breast cancer.
• Previous radiation therapy to the same breast.
• Inflammatory breast carcinoma.
• Invasive mammary carcinoma with sarcomatous, signet cell or metaplastic subtypes.
• Recurrent breast cancer.
• 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).
• Any collagen vascular disease precluding radiotherapy at the discretion of the treating radiation oncologist (particularly lupus, scleroderma, dermatomyositis, psoriatic arthritis).
• No prior stem cell transplantation.
• Any poorly controlled autoimmune conditions.
• Current use of corticosteroids or immunosuppressants.
• Any other malignancy at any site (except non-melanomatous skin cancer) \<5 years prior to study enrollment. Synchronous bilateral breast cancers are acceptable.
• Inability to tolerate core needle biopsies or pembrolizumab injection.
• Pregnant or lactating.
• Under 18 years of age.

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (2)

St. Joseph's Health Care London

London, Ontario, N6A 4V2, Canada

NOT YET RECRUITING

St. Joseph's Health Care London

London, Ontario, Canada

RECRUITING

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MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Radiation; pembrolizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Physical Phenomena

Central Study Contacts

Muriel Brackstone, MD, PhD

CONTACT

519-685-8500; muriel.brackstone@lhsc.on.ca

Kalan S Lynn, M. Sc.

CONTACT

519-646-6100; kalan.lynn@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair/Chief of General Surgery, General Surgeon, Surgical Oncologist

Model Details: Single arm open-label study of breast SBRT with immunotherapy before neoadjuvant chemotherapy

Study Record Dates

• First Submitted: May 4, 2023
• First Posted: September 23, 2025
• Study Start: January 19, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): February 1, 2029
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)