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

NCT06492759 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: STUDY00005578P30CA138292WINSHIP5835-22
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief 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 (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.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Metastatic Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (3)

• Objective response rate (ORR)

  At 9 weeks after first dose of pembrolizumab

• Overall survival (OS)

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

• Incidence of adverse events (AEs)

  Up to 90 days after the last dose of study treatment

Study Arms (1)

Treatment (radiation, pembrolizumab, chemotherapy)

EXPERIMENTAL

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 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.

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

Interventions

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Energy Type, Irradiate, Irradiated, irradiation, Radiation, Radiation Therapy, Therapy, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (radiation, pembrolizumab, chemotherapy)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: 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

Treatment (radiation, pembrolizumab, chemotherapy)

Nab-paclitaxel DRUG

Given IV

Also known as: 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

Treatment (radiation, pembrolizumab, chemotherapy)

Paclitaxel DRUG

Given IV

Also known as: 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

Treatment (radiation, pembrolizumab, chemotherapy)

Carboplatin DRUG

Given IV

Also known as: 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,

Treatment (radiation, pembrolizumab, chemotherapy)

Gemcitabine DRUG

Given IV

Also known as: 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,

Treatment (radiation, pembrolizumab, chemotherapy)

Biopsy PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE

Treatment (radiation, pembrolizumab, chemotherapy)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computed Tomography, Computerized Axial Tomography,Computerized Axial Tomography,

Treatment (radiation, pembrolizumab, chemotherapy)

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scan, bone scan, Bone Scan, Bone Scan, Bone Scan, Bone Scintigraphy

Treatment (radiation, pembrolizumab, chemotherapy)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biological Sample Collection, Biospecimen Collected, Biospecimen Collection, Specimen Collection

Treatment (radiation, pembrolizumab, chemotherapy)

Medical Chart Review OTHER

Ancillary studies

Also known as: Chart Review, Medical Chart Review

Treatment (radiation, pembrolizumab, chemotherapy)

Eligibility Criteria

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

You may qualify if:

• 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
• 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
• 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

You may not qualify if:

• 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
• \* 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

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Radiotherapy; Radiation; Therapeutics; pembrolizumab; Immunoglobulin G; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Taxes; Paclitaxel; Carboplatin; Gemcitabine; Biopsy; Specimen Handling

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Physical Phenomena; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Economics; Health Care Economics and Organizations; Coordination Complexes; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Manali Bhave, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Manali Bhave, MD

CONTACT

404-778-1900; manali.ajay.bhave@emory.edu

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: Principal Investigator

Study Record Dates

• First Submitted: July 1, 2024
• First Posted: July 9, 2024
• Study Start: October 22, 2025
• Primary Completion (Estimated): February 12, 2027
• Study Completion (Estimated): February 13, 2028
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

US (1)