Triple Negative Breast CancerPhase 1Pembro/IORTNCT02977468

Effects of MK-3475 (Pembrolizumab) on the Breast Tumor Microenvironment in Triple Negative Breast Cancer

A Phase 1 study testing Merck 3475 Pembrolizumab and Intraoperative radiation therapy (IORT) in people with Triple Negative Breast Cancer, run by Columbia University at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Assess response to pembrolizumab in both primary tumor, normal breast stroma, circulating lymphocytes and serum exosomes in treatment naive triple negative breast cancer (TNBC) patients. Read more about this study

Who is it for?: Ages 21 to 80 years, women only
Conditions the study is for: Triple Negative Breast Cancer
What is being tested?: Merck 3475 Pembrolizumab and Intraoperative radiation therapy (IORT)
Type of treatment: Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 15 participants
Where: 3 sitesUnited States
Study dates: 25 Oct 2017to 18 Jul 2024
Phase: Phase 1
Are there results?: None posted in the registry

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 21 to 80 years
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

Be willing and able to provide written informed consent/assent for the trial.
Be ≥ 21 years of age on day of signing informed consent.
Histologically proven invasive breast carcinoma with triple negative receptor status (Estrogen receptor, Progesterone receptor and HER2 negative by IHC and FISH). Patients who are weekly positive for the estrogen or progesterone receptor (i.e., < or = 10%) are eligible.
Clinically ≤ 3 cm unifocal lesion by imaging or physical examination.
Clinically node negative, no evidence of metastatic disease.
No prior anti-cancer therapy including investigational agents, radiation therapy, or breast resection within 6 months of study entry.

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Breast size B cup or larger, to allow for IORT procedure.
Have a performance status of 0 or 1 on the ECOG Performance Scale.
Demonstrate adequate organ function.
Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication.

Who cannot join

Multifocal disease within the breast.
Has primary lesion > 3 cm in size radiographically or by physical examination. Pathologically proven nodal disease at diagnosis is not allowed.
Has metastatic disease.
Has a known additional malignancy that is progressing or requires active treatment in the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, DCIS of the breast, or in situ cervical cancer that has undergone potentially curative therapy.
Patients for whom radiotherapy for breast cancer is contraindicated because of medical reasons (e.g., connective tissue disorder or prior ipsilateral breast radiation).
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.

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Has a known history of active TB (Bacillus Tuberculosis).
Has severe hypersensitivity (≥ Grade 3) to pembrolizumab or any of its excipients.
Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
Has an active infection requiring systemic therapy.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Is pregnant or breastfeeding, or expected to conceive children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
The effects of MK-3745 on the developing human fetus are unknown. For this reason and because monoclonal antibody neoplastic agents are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
Has received a live vaccine within 30 days of planned start of study therapy.
Has a medical history of allogenic stem cell transplant
Has received a solid organ transplant
Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

Emory University
Atlanta, Georgia, 30322
Loyola University Chicago
Maywood, Illinois, 60153
Columbia University Irving Medical Center
New York, New York, 10032

Other trials in United States

About this study

Official title: Effects of MK-3475 (Pembrolizumab) on the Breast Tumor Microenvironment in Triple Negative Breast Cancer With and Without Intra-operative RT: a Window of Opportunity Study

Assess response to pembrolizumab in both primary tumor, normal breast stroma, circulating lymphocytes and serum exosomes in treatment naive triple negative breast cancer (TNBC) patients.

Assess for change in tumor-infiltrating lymphocytes (TILS) both stromal (sTILS) and intraepithelial (iTILS) in newly diagnosed early stage TNBC patients treated with two doses of MK-3475 prior to lumpectomy.

Read the detailed description

This is an open-label, single-arm, single institution pre-operative "window of opportunity study" of pembrolizumab in subjects with newly diagnosed triple-negative, < 3 cm, node negative breast cancer. Subjects may not have received any prior neo/adjuvant chemotherapy, definitive surgery or radiation treatment prior to enrollment.

The goal of this project is to determine if immune modulation through treatment with MK-3475 (Pembrolizumab) in triple negative breast cancer (TNBC) patients will alter expression of immune tolerant markers [including PD-L1], within the primary tumor. Investigators hope to determine if MK-3475 exposure will change the molecular signature of breast stroma from "normal" adjacent breast tissue (non-tumor tissue) obtained prospectively at the time of breast conserving surgery (BCS) in TNBC patients. Finally, investigators will investigate how pembrolizumab alters breast stromal response to high dose radiation delivered by intraoperative radiation therapy (IORT).

Conditions: Triple Negative Breast Cancer
Being tested: Merck 3475 Pembrolizumab, Intraoperative radiation therapy (IORT)
Keywords: triple negative breast cancer, Pembrolizumab, IORT, tumor microenvironment
Medical subject headings: Triple Negative Breast Neoplasms

What participants receive

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

Merck 3475 PembrolizumabDrug
Also called Keytruda, SCH-900475, MK-3475
Participants receive Pembrolizumab by vein over about 30 minutes on Day 1 of one to two cycles.
Intraoperative radiation therapy (IORT)Radiation
Also called IORT, Zeiss Intrabeam
Participants will receive Intraoperative radiation therapy (IORT) on the day of surgery.

Study groups in NCT02977468
Study group	Role	What they receive
Single Arm open label	Experimental	Participants receive 'Merck 3475 Pembrolizumab' by vein one to two times before Intraoperative radiation therapy (IORT). The Intrabeam® Photon Radiosurgery System is a miniature electron beam-driven X-ray source which provides a point source of low energy X-rays (50 kV maximum) at the tip of a 3.2 mm diameter tube. The radiation source can be inserted into the area of interest immediately after excision of the tumor and switched on for 20-35 minutes to provide intraoperative radiotherapy accurately targeted to the tissues that are at the highest risk of local recurrence. The dosimetric characteristics and early clinical applications of this device have been well studied and this is the device which was utilized in the international TARGIT trial. Receives: Drug: Merck 3475 Pembrolizumab; Radiation: Intraoperative radiation therapy (IORT)

What is being measured

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

Number of subjects with significant mean percent change in TILs
This outcome measure is designed to determine if immune modulation therapy with MK-3475 will increase TILs in newly diagnosed TNBC tumors. The mean percent change in TILS in tumor tissue from initial core biopsy samples will be compared with pathology samples from definitive surgery after two cycles of MK-3475.
Measured: 3 months

Timeline

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

25 Oct 201718 Jul 2024

First posted30 Nov 2016 (estimated)
Study start25 Oct 2017
Primary completion18 Jul 2024
Study completion18 Jul 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Triple Negative Breast CancerStudies of the same condition, open and under way.
More trials run by Columbia UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02977468
Sponsor's protocol ID: AAAQ7863
Acronym: Pembro/IORT
Status last verified: Oct 2026
First submitted: 28 Nov 2016
Last updated: 21 Oct 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided

Study at a glance

From the registry record, last updated by the sponsor on 21 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effects of MK-3475 (Pembrolizumab) on the Breast Tumor Microenvironment in Triple Negative Breast Cancer With and Without Intra-operative RT: a Window of Opportunity Study
ClinicalTrials.gov ID: NCT02977468
Acronym / sponsor ID: Pembro/IORT / AAAQ7863
Conditions: Triple Negative Breast Cancer
Keywords: triple negative breast cancer, Pembrolizumab, IORT, tumor microenvironment
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 15 participants (actual)
Lead sponsor: Columbia UniversityUniversity, hospital or other
Collaborators: Merck Sharp & Dohme LLC
Study start: 25 Oct 2017 (actual)
Primary completion: 18 Jul 2024 (actual)
Study completion: 18 Jul 2024 (actual)
First posted: 30 Nov 2016 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Assess response to pembrolizumab in both primary tumor, normal breast stroma, circulating lymphocytes and serum exosomes in treatment naive triple negative breast cancer (TNBC) patients.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Single Arm open label	Experimental	Drug: Merck 3475 Pembrolizumab, Radiation: Intraoperative radiation therapy (IORT)Participants receive 'Merck 3475 Pembrolizumab' by vein one to two times before Intraoperative radiation therapy (IORT). The Intrabeam® Photon Radiosurgery System is a miniature electron beam-driven X-ray source which provides a point source of low energy X-rays (50 kV maximum) at the tip of a 3.2 mm diameter tube. The radiation source can be inserted into the area of interest immediately after excision of the tumor and switched on for 20-35 minutes to provide intraoperative radiotherapy accurately targeted to the tissues that are at the highest risk of local recurrence. The dosimetric characteristics and early clinical applications of this device have been well studied and this is the device which was utilized in the international TARGIT trial.

Who may qualify

Ages: 21 to 80 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Be willing and able to provide written informed consent/assent for the trial.
Be ≥ 21 years of age on day of signing informed consent.
Histologically proven invasive breast carcinoma with triple negative receptor status (Estrogen receptor, Progesterone receptor and HER2 negative by IHC and FISH). Patients who are weekly positive for the estrogen or progesterone receptor (i.e., < or = 10%) are eligible.
Clinically ≤ 3 cm unifocal lesion by imaging or physical examination.
Clinically node negative, no evidence of metastatic disease.

Key exclusion criteria (21 listed)

Multifocal disease within the breast.
Has primary lesion > 3 cm in size radiographically or by physical examination. Pathologically proven nodal disease at diagnosis is not allowed.
Has metastatic disease.
Has a known additional malignancy that is progressing or requires active treatment in the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, DCIS of the breast, or in situ cervical cancer that has undergone potentially curative therapy.
Patients for whom radiotherapy for breast cancer is contraindicated because of medical reasons (e.g., connective tissue disorder or prior ipsilateral breast radiation).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Merck 3475 PembrolizumabAlso: Keytruda, SCH-900475, MK-3475Participants receive Pembrolizumab by vein over about 30 minutes on Day 1 of one to two cycles.	Drug	Single Arm open label
Intraoperative radiation therapy (IORT)Also: IORT, Zeiss IntrabeamParticipants will receive Intraoperative radiation therapy (IORT) on the day of surgery.	Radiation	Single Arm open label

Primary outcome

Number of subjects with significant mean percent change in TILs
Time frame: 3 months
This outcome measure is designed to determine if immune modulation therapy with MK-3475 will increase TILs in newly diagnosed TNBC tumors. The mean percent change in TILS in tumor tissue from initial core biopsy samples will be compared with pathology samples from definitive surgery after two cycles of MK-3475.

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2026.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Eileen Connolly, MD principal investigator

Assistant Professor Of Radiation Oncology

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Merck 3475 Pembrolizumab and Intraoperative radiation therapy (IORT) in people with Triple Negative Breast Cancer, run by Columbia University at 3 sites in United States.

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 11 inclusion and 21 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: finished, as of the sponsor's last update on 21 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of subjects with significant mean percent change in TILs (time frame: 3 months). 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 NCT02977468.

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 21 Oct 2026.