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Back|NCT06492759Recruiting
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

Phase
Phase 2
Sponsor
Emory University
Enrollment
29
Timeline
Jan 2026 → Feb 2028
About This Study

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.

Eligibility Criteria

Inclusion Criteria

  • 1Biopsy proven metastatic PD-L1 positive triple negative breast cancer with at least 2 sites of measurable metastatic disease on imaging
  • 2Estrogen receptor (ER) and progesterone receptor (PR) negativity are defined as ≤ 10% of cells expressing hormonal receptors via immunohistochemistry (IHC) analysis
  • 3HER2 negativity is defined as either of the following by local laboratory assessment
  • 4In situ hybridization (ISH) non-amplified (ratio of HER2 to CEP17 \< 2.0 or single probe average HER2 gene copy number \< 4 signals/cell) or
  • 5IHC 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
  • 6PD-L1 positive as defined by Dako 22c3 assay PD-L1 combined positive score (CPS) ≥ 10
  • 7Appropriate stage for study entry based on the following diagnostic workup:
  • 8History and physical examination within 60 days prior to registration
  • 9Clinical 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
  • 10Patient must be eligible for radiotherapy as determined by their treating physician
  • 11Patient must be eligible for immunotherapy and taxane chemotherapy as determined by their treating physician
  • 12At least 1 metastatic site amenable to high dose radiotherapy
  • 13Be willing and able to provide written informed consent for the trial
  • 14Ages ≥ 18 years of age
  • 15Biopsy proven metastatic PD-L1 positive triple negative breast cancer with at least 2 sites of measurable metastatic disease on imaging
  • 16Estrogen receptor (ER) and progesterone receptor (PR) negativity are defined as ≤ 10% of cells expressing hormonal receptors via immunohistochemistry (IHC) analysis
  • 17HER2 negativity is defined as either of the following by local laboratory assessment
  • 18In situ hybridization (ISH) non-amplified (ratio of HER2 to CEP17 \< 2.0 or single probe average HER2 gene copy number \< 4 signals/cell) or
  • 19IHC 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
  • 20PD-L1 positive as defined by Dako 22c3 assay PD-L1 combined positive score (CPS) ≥ 10
  • 21Appropriate stage for study entry based on the following diagnostic workup:
  • 22History and physical examination within 60 days prior to registration
  • 23Clinical 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
  • 24Patient must be eligible for radiotherapy as determined by their treating physician
  • 25Patient must be eligible for immunotherapy and taxane chemotherapy as determined by their treating physician
  • 26At least 1 metastatic site amenable to high dose radiotherapy
  • 27Be willing and able to provide written informed consent for the trial
  • 28Ages ≥ 18 years of age
  • 29Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2, Karnofsky performance status (KPS) ≥ 60%
  • 30Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1)
  • 31Absolute neutrophil count ≥ 1500/mcL (obtained within 14 days prior to first study treatment)
  • 32Platelet count ≥ 100,000/mcL (obtained within 14 days prior to first study treatment)
  • 33Hemoglobin ≥ 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)
  • 34Aspartate 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):
  • 35\* Patients with documented liver metastases: AST and ALT ≤ 5 x ULN
  • 36Serum bilirubin ≤ 1.5 x ULN (obtained within 14 days prior to first study treatment)
  • 37\* Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled
  • 38Calculated creatinine clearance ≥ 30 mL/min (obtained within 14 days prior to first study treatment)
  • 39For females of child-bearing potential, negative serum or urine pregnancy test within 14 days prior to radiation simulation
  • 40The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
  • 41Prior Treatment:
  • 42Patients 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
  • 43Patients must have not active wound healing issues from surgery and sufficient resolution of surgical side effects, per physician assessment, at time of radiotherapy
  • 44Patients are not eligible if they have received chemotherapy in the advanced/metastatic setting
  • 45During 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
  • 46Patients may have received bisphosphonates or rank ligand inhibitors prior to enrollment on study

Exclusion Criteria

  • 1Prior 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
  • 2Previous radiation to the metastases to be treated with radiation on this protocol
  • 3Untreated central nervous system (CNS) disease (patients with stable CNS disease for at least 28 days and asymptomatic treated CNS metastases are permitted)
  • 4Uncontrolled pleural effusion, pericardial effusion or ascites
  • 5\* Patients with indwelling catheters (e.g., Pleurx) are allowed
  • 6Uncontrolled 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
  • 7\* Patients who are receiving bisphosphonate therapy specifically to prevent skeletal prevents and who do not have a history of clinically significant hypercalcemia are eligible
  • 8History (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
  • 9Use of chronic systemic glucocorticoid or immunosuppressive medications at time of enrollment (prednisone or equivalent steroid dose of \> 10mg for \> 2 weeks)
  • 10Prior allogeneic stem cell or solid organ transplantation
  • 11Severe, 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
  • 12Acute bacterial or fungal infection requiring IV antibiotics at time of registration
  • 13History 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
  • 14\* History of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • 15Chronic obstructive pulmonary disease (COPD) or other respiratory illness requiring hospitalization at time of registration
  • 16HIV positive with CD4 count \< 200 cells/ microliter
  • 17Has 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
  • 18Has 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:
  • 19Major 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
  • 20Known hypersensitivity to nab-paclitaxel or to any of the excipients
  • 21Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • 22Is 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

Locations

1 site participating in this study

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia 30322

Recruiting

Manali A. Bhave, MD

Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →