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Breast CancerPhase 2BRINKNCT07188246

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

A Phase 2 study testing Radiation and Pembrolizumab (KEYTRUDA®) in people with Breast Cancer and Breast Cancer Stage II, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 2 sites in Canada.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Radiation and Pembrolizumab (KEYTRUDA®)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
2 sitesCanada
Study dates
19 Jan 2026to Feb 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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.
  • 18 years of age or older.
  • Able to provide informed consent.

Who cannot join

  • 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.
Show all 17Show fewer
  • 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.
  • Inability or unwillingness to provide informed consent.
  • Inability or unwillingness to complete study assessments/interventions and follow-up assessments.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Muriel Brackstone, MD, PhD contact

519-685-8500 ext. 58712

muriel.brackstone@lhsc.on.ca

Kalan S Lynn, M. Sc. contact

519-646-6100 ext. 61384

kalan.lynn@lhsc.on.ca

Canada2 sites, 2 recruiting

  • St. Joseph's Health Care London

    London, Ontario, N6A 4V2

    Not yet recruiting

  • St. Joseph's Health Care London

    London, Ontario

    Muriel Brackstone, MD, PhD, 519-685-8712, Muriel.Brackstone@lhsc.on.ca

    Recruiting

Other trials in Canada

About this study

Official title: 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 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).

Read the 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.

Being tested
Radiation, Pembrolizumab (KEYTRUDA®)
Keywords
Immunotherapy, Pembrolizumab, Breast SBRT
Medical subject headings
Breast Neoplasms, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RadiationRadiation

    Stereotactic body radiation therapy to the breast

  • Pembrolizumab (KEYTRUDA®)Drug

    Two injections

Study groups in NCT07188246
Study groupRoleWhat they receive
SBRT with PembrolizumabExperimentalStereotactic body radiation therapy delivered to the main breast tumour with 2 injections of pembrolizumab (Keytruda), completed prior to neoadjuvant chemotherapy.
Receives: Radiation: Radiation; Drug: Pembrolizumab (KEYTRUDA®)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathological Complete Response

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

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

Secondary outcomes (4)

  1. Immune priming

    To evaluate the degree of immune priming in this regimen compared descriptively to TRIO Trial

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

  2. Breast and skin tissue adverse events to evaluate toxicity of treatment

    Toxicity to surrounding breast and skin tissue, defined by ≥ grade 2 fibrosis.

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

  3. Treatment related adverse event

    Adverse events relating to the interventional radiation or pembrolizumab defined by ≥ grade 3

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

  4. Local Recurrence Rates

    Ipsilateral breast recurrence rate.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Sep 2025
  2. Study start19 Jan 2026
  3. Primary completionJul 2027 (estimated)
  4. Study completionFeb 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Single arm open-label study of breast SBRT with immunotherapy before neoadjuvant chemotherapy
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07188246
Sponsor's protocol ID
122109
Acronym
BRINK
Status last verified
Feb 2026
First submitted
4 May 2023
Last updated
11 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Barendsen GW. Dose fractionation, dose rate and iso-effect relationships for normal tissue responses. Int J Radiat Oncol Biol Phys. 1982 Nov;8(11):1981-97. doi: 10.1016/0360-3016(82)90459-x. No abstract available.

    PubMed 6759484

  • Beal K, McCormick B, Zelefsky MJ, Borgen P, Fey J, Goldberg J, Cohen GN, Sacchini V. Single-fraction intraoperative radiotherapy for breast cancer: early cosmetic results. Int J Radiat Oncol Biol Phys. 2007 Sep 1;69(1):19-24. doi: 10.1016/j.ijrobp.2007.02.010. Epub 2007 Apr 18.

    PubMed 17446003

  • Blitzblau RC, Arya R, Yoo S, Baker JA, Chang Z, Palta M, Duffy E, Horton JK. A phase 1 trial of preoperative partial breast radiation therapy: Patient selection, target delineation, and dose delivery. Pract Radiat Oncol. 2015 Sep-Oct;5(5):e513-e520. doi: 10.1016/j.prro.2015.02.002. Epub 2015 Mar 31.

    PubMed 25834942

  • Bondiau PY, Courdi A, Bahadoran P, Chamorey E, Queille-Roussel C, Lallement M, Birtwisle-Peyrottes I, Chapellier C, Pacquelet-Cheli S, Ferrero JM. Phase 1 clinical trial of stereotactic body radiation therapy concomitant with neoadjuvant chemotherapy for breast cancer. Int J Radiat Oncol Biol Phys. 2013 Apr 1;85(5):1193-9. doi: 10.1016/j.ijrobp.2012.10.034. Epub 2013 Jan 16.

    PubMed 23332384

  • Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im SA, Yusof MM, Gallardo C, Lipatov O, Barrios CH, Holgado E, Iwata H, Masuda N, Otero MT, Gokmen E, Loi S, Guo Z, Zhao J, Aktan G, Karantza V, Schmid P; KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020 Dec 5;396(10265):1817-1828. doi: 10.1016/S0140-6736(20)32531-9.

    PubMed 33278935

  • Cortes J, Rugo HS, Cescon DW, Im SA, Yusof MM, Gallardo C, Lipatov O, Barrios CH, Perez-Garcia J, Iwata H, Masuda N, Torregroza Otero M, Gokmen E, Loi S, Guo Z, Zhou X, Karantza V, Pan W, Schmid P; KEYNOTE-355 Investigators. Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2022 Jul 21;387(3):217-226. doi: 10.1056/NEJMoa2202809.

    PubMed 35857659

  • Dai M, Yip YY, Hellstrom I, Hellstrom KE. Curing mice with large tumors by locally delivering combinations of immunomodulatory antibodies. Clin Cancer Res. 2015 Mar 1;21(5):1127-38. doi: 10.1158/1078-0432.CCR-14-1339. Epub 2014 Aug 20.

    PubMed 25142145

  • Demaria S, Romano E, Brackstone M, Formenti SC. Immune induction strategies to enhance responses to PD-1 blockade: lessons from the TONIC trial. J Immunother Cancer. 2019 Nov 21;7(1):318. doi: 10.1186/s40425-019-0783-x.

    PubMed 31752991

  • Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC, Demaria S. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res. 2009 Sep 1;15(17):5379-88. doi: 10.1158/1078-0432.CCR-09-0265. Epub 2009 Aug 25.

    PubMed 19706802

  • Dunlap NE, Cai J, Biedermann GB, Yang W, Benedict SH, Sheng K, Schefter TE, Kavanagh BD, Larner JM. Chest wall volume receiving >30 Gy predicts risk of severe pain and/or rib fracture after lung stereotactic body radiotherapy. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3):796-801. doi: 10.1016/j.ijrobp.2009.02.027. Epub 2009 May 8.

    PubMed 19427740

  • Eaton DJ, Best B, Brew-Graves C, Duck S, Ghaus T, Gonzalez R, Pigott K, Reynolds C, Williams NR, Keshtgar MR. In vivo dosimetry for single-fraction targeted intraoperative radiotherapy (TARGIT) for breast cancer. Int J Radiat Oncol Biol Phys. 2012 Apr 1;82(5):e819-24. doi: 10.1016/j.ijrobp.2011.11.012. Epub 2012 Jan 31.

    PubMed 22300571

  • Edwards AA, Keggin E, Plowman PN. The developing role for intensity-modulated radiation therapy (IMRT) in the non-surgical treatment of brain metastases. Br J Radiol. 2010 Feb;83(986):133-6. doi: 10.1259/bjr/28596848. Epub 2009 Dec 17.

    PubMed 20019176

  • Glencer AC, Wong JM, Hylton NM, Krings G, McCune E, Rothschild HT, Loveday TA, Alvarado MD, Esserman LJ, Campbell MJ. Modulation of the immune microenvironment of high-risk ductal carcinoma in situ by intralesional pembrolizumab injection. NPJ Breast Cancer. 2021 May 25;7(1):59. doi: 10.1038/s41523-021-00267-z.

    PubMed 34035311

  • Greco C, Zelefsky MJ, Lovelock M, Fuks Z, Hunt M, Rosenzweig K, Zatcky J, Kim B, Yamada Y. Predictors of local control after single-dose stereotactic image-guided intensity-modulated radiotherapy for extracranial metastases. Int J Radiat Oncol Biol Phys. 2011 Mar 15;79(4):1151-7. doi: 10.1016/j.ijrobp.2009.12.038. Epub 2010 May 25.

    PubMed 20510537

  • Hong WX, Haebe S, Lee AS, Westphalen CB, Norton JA, Jiang W, Levy R. Intratumoral Immunotherapy for Early-stage Solid Tumors. Clin Cancer Res. 2020 Jul 1;26(13):3091-3099. doi: 10.1158/1078-0432.CCR-19-3642. Epub 2020 Feb 18.

    PubMed 32071116

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Radiation and Pembrolizumab (KEYTRUDA®) in people with Breast Cancer and Breast Cancer Stage II, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 2 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 11 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Muriel Brackstone, MD, PhD (519-685-8500 ext. 58712, muriel.brackstone@lhsc.on.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological Complete Response (time frame: Measured at time of surgery, typically 6 months after enrollment in trial.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07188246, which also lists 38 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2026.

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