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AzTrials

Anatomic Stage IV Breast Cancer AJCC v8Phase 2NCT06492759

High Dose Radiation Therapy With Pembrolizumab and Chemotherapy for the Treatment of Patients With PD-L1 Positive Metastatic Triple Negative Breast Cancer

A Phase 2 study testing Radiation Therapy, Pembrolizumab and Nab-paclitaxel in people with Anatomic Stage IV Breast Cancer AJCC v8 and Metastatic Triple-Negative Breast Carcinoma, run by Emory University at 1 site in United States.

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 phase II trial tests how well radiation therapy with pembrolizumab and chemotherapy (paclitaxel or nab-paclitaxel or carboplatin and gemcitabine) works in treating patients with PD-L1 positive triple negative breast cancer that has spread from where it first started (primary site) to other places in the body… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Radiation Therapy, Pembrolizumab and Nab-paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteUnited States
Study dates
22 Oct 2025to 13 Feb 2028
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

  • Biopsy proven metastatic PD-L1 positive triple negative breast cancer with at least 2 sites of measurable metastatic disease on imaging
  • Estrogen receptor (ER) and progesterone receptor (PR) negativity are defined as ≤ 10% of cells expressing hormonal receptors via immunohistochemistry (IHC) analysis
  • HER2 negativity is defined as either of the following by local laboratory assessment
  • In situ hybridization (ISH) non-amplified (ratio of HER2 to CEP17 < 2.0 or single probe average HER2 gene copy number < 4 signals/cell) or
  • IHC 0 or IHC 1+. If more than one test result is available and not all results meet the inclusion criterion definition, all results should be discussed with the Medical Monitor to establish eligibility of the patient
  • PD-L1 positive as defined by Dako 22c3 assay PD-L1 combined positive score (CPS) ≥ 10
Show all 46Show fewer
  • Appropriate stage for study entry based on the following diagnostic workup:
  • History and physical examination within 60 days prior to registration
  • Clinical grade CT scans of the chest, abdomen, and pelvis with radionuclide bone scan or whole body positron emission tomography (PET)/CT documenting metastatic disease within 4 weeks of the start of radiotherapy on this protocol with or without magnetic resonance imaging (MRI), as needed, documenting site of metastatic disease to be treated on protocol
  • Patient must be eligible for radiotherapy as determined by their treating physician
  • Patient must be eligible for immunotherapy and taxane chemotherapy as determined by their treating physician
  • At least 1 metastatic site amenable to high dose radiotherapy
  • Be willing and able to provide written informed consent for the trial
  • Ages ≥ 18 years of age
  • Biopsy proven metastatic PD-L1 positive triple negative breast cancer with at least 2 sites of measurable metastatic disease on imaging
  • Estrogen receptor (ER) and progesterone receptor (PR) negativity are defined as ≤ 10% of cells expressing hormonal receptors via immunohistochemistry (IHC) analysis
  • HER2 negativity is defined as either of the following by local laboratory assessment
  • In situ hybridization (ISH) non-amplified (ratio of HER2 to CEP17 < 2.0 or single probe average HER2 gene copy number < 4 signals/cell) or
  • IHC 0 or IHC 1+. If more than one test result is available and not all results meet the inclusion criterion definition, all results should be discussed with the Medical Monitor to establish eligibility of the patient
  • PD-L1 positive as defined by Dako 22c3 assay PD-L1 combined positive score (CPS) ≥ 10
  • Appropriate stage for study entry based on the following diagnostic workup:
  • History and physical examination within 60 days prior to registration
  • Clinical grade CT scans of the chest, abdomen, and pelvis with radionuclide bone scan or whole body positron emission tomography (PET)/CT documenting metastatic disease within 4 weeks of the start of radiotherapy on this protocol with or without magnetic resonance imaging (MRI), as needed, documenting site of metastatic disease to be treated on protocol
  • Patient must be eligible for radiotherapy as determined by their treating physician
  • Patient must be eligible for immunotherapy and taxane chemotherapy as determined by their treating physician
  • At least 1 metastatic site amenable to high dose radiotherapy
  • Be willing and able to provide written informed consent for the trial
  • Ages ≥ 18 years of age
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2, Karnofsky performance status (KPS) ≥ 60%
  • Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1)
  • Absolute neutrophil count ≥ 1500/mcL (obtained within 14 days prior to first study treatment)
  • Platelet count ≥ 100,000/mcL (obtained within 14 days prior to first study treatment)
  • Hemoglobin ≥ 9.0 g/dL (obtained within 14 days prior to first study treatment) (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] ≥ 9.0g/dL is acceptable)
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x the upper limit of normal (ULN) with the following exceptions (obtained within 14 days prior to first study treatment):
  • Patients with documented liver metastases: AST and ALT ≤ 5 x ULN
  • Serum bilirubin ≤ 1.5 x ULN (obtained within 14 days prior to first study treatment)
  • Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled
  • Calculated creatinine clearance ≥ 30 mL/min (obtained within 14 days prior to first study treatment)
  • For females of child-bearing potential, negative serum or urine pregnancy test within 14 days prior to radiation simulation
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
  • Prior Treatment:
  • Patients may or may not have received radiotherapy or neoadjuvant or adjuvant chemotherapy in the treatment of their initial, non-metastatic breast cancer, but must be entered on study after their last dose of radiotherapy, last cycle of chemotherapy and biologic therapy (if applicable) and have sufficient resolution of side effects per physician assessment at time of radiotherapy. Prior immunotherapy for treatment of early stage breast cancer is allowed if metastatic recurrence occurs ≥ 6 months after last dose of immunotherapy
  • Patients must have not active wound healing issues from surgery and sufficient resolution of surgical side effects, per physician assessment, at time of radiotherapy
  • Patients are not eligible if they have received chemotherapy in the advanced/metastatic setting
  • During radiotherapy, no other investigation or commercial agents or therapy for cancer other than bisphosphonate or receptor activator nuclear kappaB ligand (RANK-L) inhibitor, pembrolizumab, and nab-paclitaxel, paclitaxel, carboplatin or gemcitabine should be administered
  • Patients may have received bisphosphonates or rank ligand inhibitors prior to enrollment on study

Who cannot join

  • Prior chemotherapy or targeted therapy for metastatic triple negative breast cancer before start of pembrolizumab plus partner chemotherapy. Prior chemotherapy (including taxanes) administered in the context of curative therapy (if treatment was completed > 6 months) prior to enrollment into the trial is allowed
  • Previous radiation to the metastases to be treated with radiation on this protocol
  • Untreated central nervous system (CNS) disease (patients with stable CNS disease for at least 28 days and asymptomatic treated CNS metastases are permitted)
  • Uncontrolled pleural effusion, pericardial effusion or ascites
  • Patients with indwelling catheters (e.g., Pleurx) are allowed
  • Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
Show all 22Show fewer
  • Patients who are receiving bisphosphonate therapy specifically to prevent skeletal prevents and who do not have a history of clinically significant hypercalcemia are eligible
  • History (Hx) of autoimmune disease that has required systemic treatment (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
  • Use of chronic systemic glucocorticoid or immunosuppressive medications at time of enrollment (prednisone or equivalent steroid dose of > 10mg for > 2 weeks)
  • Prior allogeneic stem cell or solid organ transplantation
  • Severe, active co-morbidity such as congestive heart failure (CHF) or unstable angina within last 6 months, transmural myocardial infarction (MI) within the last 6 months
  • Acute bacterial or fungal infection requiring IV antibiotics at time of registration
  • History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan
  • History of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Chronic obstructive pulmonary disease (COPD) or other respiratory illness requiring hospitalization at time of registration
  • HIV positive with CD4 count < 200 cells/ microliter
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy. Indolent cancers (such as low risk prostate or in-situ cancers) that are not being treated, are acceptable
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. Examples include:
  • Major surgical procedure within 28 days prior to randomization or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis
  • Known hypersensitivity to nab-paclitaxel or to any of the excipients
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 90 days after the last dose of trial treatment

Trial locations and contacts

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

Manali Bhave, MD contact

404-778-1900

manali.ajay.bhave@emory.edu

United States1 site, 1 recruiting

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

    Ashley Lynn Trumbull, 404-778-3969, ashley.lynn.trumbull@emory.edu

    Manali A. Bhave, MD

    Recruiting

Other trials in United States

About this study

Official title: A Phase II Study of High Dose Radiotherapy in Combination With Pembrolizumab Plus Chemotherapy in Patients With PD-L1 Positive Metastatic Triple Negative Breast Cancer

This phase II trial tests how well radiation therapy with pembrolizumab and chemotherapy (paclitaxel or nab-paclitaxel or carboplatin and gemcitabine) works in treating patients with PD-L1 positive triple negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. Carboplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill cancer cells. High dose radiation therapy with pembrolizumab and chemotherapy may effective in treating patients with PD-L1 positive metastatic triple negative breast cancer.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the 12 month progression-free survival (PFS) in PD-L1 positive, triple negative breast cancer patients treated with high dose radiotherapy before and concurrently with the first cycle of pembrolizumab plus chemotherapy.

SECONDARY OBJECTIVES:

  1. To evaluate the objective response rate (ORR) in non-irradiated lesions nine weeks after the first dose of pembrolizumab in PD-L1 positive, triple negative breast cancer patients treated with high dose radiotherapy before and concurrently with the first cycle pembrolizumab plus chemotherapy (ORR per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).

II. To determine if targeted, high dose radiotherapy to up to 3 metastatic sites in combination with pembrolizumab plus chemotherapy in patients with metastatic triple negative breast cancer (> 2 sites) adversely increases the frequency and severity of toxicities associated with radiotherapy or pembrolizumab plus chemotherapy when administered separately.

III. To determine progression-free survival (PFS) in breast cancer patients treated with high dose radiotherapy, pembrolizumab, and chemotherapy.

EXPLORATORY OBJECTIVES:

  1. To collect, store, and analyze circulating tumor deoxyribonucleic acid (ctDNA) in metastatic breast cancer patients treated with radiotherapy, pembrolizumab, and chemotherapy to determine the relationship between ctDNA and PFS and ORR.

II. To collect, store and analyze tumor tissue from a non-irradiated metastatic breast cancer site before and after radiotherapy to explore the immune tumor microenvironment and the immunoscore, and the relationship between the immunoscore and ORR and PFS in metastatic breast cancer patients treated with pembrolizumab and chemotherapy.

OUTLINE:

Patients undergo radiation therapy once every other day for 3 doses. Beginning within 48 hours of their first dose of radiation therapy, patients receive standard of care pembrolizumab intravenously (IV) on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also receive 1 of 3 standard of care chemotherapy options: nab-paclitaxel IV on days 1, 8, and 15 of each cycle, or paclitaxel IV on days 1, 8, and 15 of each cycle, or carboplatin IV and gemcitabine IV on days 1 and 8 of each cycle. Cycles of nab-paclitaxel and paclitaxel repeat every 28 days and cycles of carboplatin and gemcitabine repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a biopsy at baseline and 2 weeks after radiation therapy and also undergo computed tomography (CT) scans, bone scans and blood sample collections throughout the trial.

After completion of study treatment, patients are followed up every 12 weeks.

Being tested
Radiation Therapy, Pembrolizumab, Nab-paclitaxel, Paclitaxel, Carboplatin
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.

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Energy Type, Irradiate, Irradiated, irradiation, Radiation, Radiation Therapy, Therapy, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

    Undergo radiation therapy

  • PembrolizumabBiological

    Also called 1374853-91-4, BCD-201, Immunoglobulin G4, Anti-(Human Programmed Cell Death 1); Humanized Mouse Monoclonal (228-L-proline(H10-S>P))gamma 4 Heavy Chain (134-218')-disulfide with Humanized, Monoclonal Kappa Light Chain Dimer (226-226'':229-229'')-bisdisulfide, Keytruda, Lambrolizumab, MK-3475, PEMBROLIZUMAB, Pembrolizumab, Biosimilar BCD-201, SCH 900475

    Given IV

  • Nab-paclitaxelDrug

    Also called ABI 007, ABI-007, ABI-007, Abraxane, Abraxane, Albumin-bound Paclitaxel, Albumin-Stabilized Nanoparticle Paclitaxel, Nanoparticle Albumin-bound, Paclitaxel, nanoparticle paclitaxel, Nanoparticle Paclitaxel, Paclitaxel Albumin, paclitaxel albumin-stabilized nanoparticle formulation, Paclitaxel nanoparticle albumin-bound,, Paclitaxel Protein-Bound, protein-bound paclitaxel, Protein-bound Paclitaxel

    Given IV

  • PaclitaxelDrug

    Also called 33069-62-4,5Beta,20-epoxy-1,2alpha,4,7beta,10beta,13alpha-hexahydroxytax-11-en-9-one,4,10-Diacetate 2-Benzoate 13-Ester with (2R,3S)-N-Benzoyl-3-phenylisoserine, [2aR-[2a Alpha,4beta,4a beta,6beta

    Given IV

  • CarboplatinDrug

    Also called SP-4-2)-diammine[1,1-cyclobutanedicarboxylato(2--)-O,O']platinum, 1,1-cyclobutanedicarboxylic acid platinum complex, 41575-94-4, Blastocarb, Carboplat, CARBOPLATIN,, Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, CBDCA, cis-diammine(1,1-cyclobutanedicarboxylato) platinum(II),, complex, 41575-94-4, Blastocarb, Carboplat, CARBOPLATIN, Carboplatin, Carboplatin Hexal, Carboplatino, Carboplatinum,, Carbosin, Carbosol, Carbotec, CBDCA, cis-diammine(1,1-cyclobutanedicarboxylato) platinum(II), Cis-Diammine(cyclobutane-1,1-dicarboxylato)platinum,

    Given IV

  • GemcitabineDrug

    Also called 1-(2-Oxo-4-amino-1,2-dihydropyrimidin-1-yl)-2-deoxy-2,2-difluororibose, 2'Deoxy-2',2'-Difluorocytidine, 95058-81-4, dFdC, dFdCyd, Difluorodeoxycytidine, Gemcitabine, GEMCITABINE,

    Given IV

  • BiopsyProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE

    Undergo biopsy

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computed Tomography, Computerized Axial Tomography,Computerized Axial Tomography,

    Undergo CT

  • Bone ScanProcedure or surgery

    Also called Bone Scan, bone scan, Bone Scan, Bone Scan, Bone Scan, Bone Scintigraphy

    Undergo bone scan

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biological Sample Collection, Biospecimen Collected, Biospecimen Collection, Specimen Collection

    Undergo blood sample collection

  • Medical Chart ReviewOther

    Also called Chart Review, Medical Chart Review

    Ancillary studies

Study groups in NCT06492759
Study groupRoleWhat they receive
Treatment (radiation, pembrolizumab, chemotherapy)ExperimentalPatients undergo radiation therapy once every other day for 3 doses. Beginning within 48 hours of their first dose of radiation therapy, patients receive standard of care pembrolizumab IV on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also receive 1 of 3 standard of care chemotherapy options: nab-paclitaxel IV on days 1, 8, and 15 of each cycle, or paclitaxel IV on days 1, 8, and 15 of each cycle, or carboplatin IV and gemcitabine IV on days 1 and 8 of each cycle. Cycles of nab-paclitaxel and paclitaxel repeat every 28 days and cycles of carboplatin and gemcitabine repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a biopsy at baseline and 2 weeks after radiation therapy and also undergo CT scans, bone scans and blood sample collections throughout the trial.
Receives: Radiation: Radiation Therapy; Biological: Pembrolizumab; Drug: Nab-paclitaxel; Drug: Paclitaxel; Drug: Carboplatin; Drug: Gemcitabine; Procedure: Biopsy; Procedure: Computed Tomography; Procedure: Bone Scan; Procedure: Biospecimen Collection; Other: Medical Chart Review

What is being measured

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

  1. Progression-free survival (PFS)

    Progressive disease will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. PFS will be estimated using the Kaplan-Meier method, and a 95% confidence interval for 1-year PFS will be estimated using the Greenwood formula. The 1-year PFS estimate will be compared to a null value of 30% using a one-sample log-rank test.

    Measured: From start of radiation therapy to progression or death, assessed at 1 year

Secondary outcomes (3)

  1. Objective response rate (ORR)

    Response will be defined by partial or complete response on imaging using RECIST version 1.1. ORR will be estimated as a proportion, with an exact 95% confidence interval estimated using the Clopper-Pearson method.

    Measured: At 9 weeks after first dose of pembrolizumab

  2. Overall survival (OS)

    OS will be estimated using the Kaplan-Meier method, and median survival will be calculated. A 95% confidence interval will be estimated using the Brookmeyer-Crowley approach.

    Measured: From start of radiation therapy to death, assessed up to 2 years

  3. Incidence of adverse events (AEs)

    AEs will be determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5. Frequencies and percentages will be used to summarize safety events.

    Measured: Up to 90 days after the last dose of study treatment

Timeline

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

  1. First posted9 Jul 2024
  2. Study start22 Oct 2025
  3. Primary completion12 Feb 2027 (estimated)
  4. Study completion13 Feb 2028 (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
Masking
None (open label)
Enrolment
29 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06492759
Sponsor's protocol ID
STUDY00005578
Other IDs
P30CA138292, WINSHIP5835-22
Status last verified
Apr 2026
First submitted
1 Jul 2024
Last updated
17 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Radiation Therapy, Pembrolizumab and Nab-paclitaxel in people with Anatomic Stage IV Breast Cancer AJCC v8 and Metastatic Triple-Negative Breast Carcinoma, run by Emory University at 1 site 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 46 inclusion and 22 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 17 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 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 Manali Bhave, MD (404-778-1900, manali.ajay.bhave@emory.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: From start of radiation therapy to progression or death, assessed at 1 year). 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 NCT06492759.

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 17 Apr 2026.

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