NCT06492759

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

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 29 (estimated)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVE: I. 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: I. 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: I. 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.

Conditions

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

Interventions

Type	Name	Description
RADIATION	Radiation Therapy	Undergo radiation therapy
BIOLOGICAL	Pembrolizumab	Given IV
DRUG	Nab-paclitaxel	Given IV
DRUG	Paclitaxel	Given IV
DRUG	Carboplatin	Given IV
DRUG	Gemcitabine	Given IV
PROCEDURE	Biopsy	Undergo biopsy
PROCEDURE	Computed Tomography	Undergo CT
PROCEDURE	Bone Scan	Undergo bone scan
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
OTHER	Medical Chart Review	Ancillary studies

Timeline

• Start date: 2025-10-22
• Primary completion: 2027-02-12
• Completion: 2028-02-13
• First posted: 2024-07-09
• Last updated: 2026-04-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study