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.
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
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
Single group
Radiation Therapy
RadiationUndergo radiation therapy
Pembrolizumab
Biological/VaccineGiven IV
Nab-paclitaxel
DrugGiven IV
Paclitaxel
DrugGiven IV
Carboplatin
DrugGiven IV
Gemcitabine
DrugGiven IV
Biopsy
Procedure/SurgeryUndergo biopsy
Computed Tomography
Procedure/SurgeryUndergo CT
Bone Scan
Procedure/SurgeryUndergo bone scan
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Medical Chart Review
Other interventionAncillary studies
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.
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.
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.
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.
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Emory University
Lead sponsor
National Cancer Institute (NCI)
Collaborator
