Immune-checkpoint Blockade After Partial Breast Irradiation by Pembrolizumab in Early TNBC (KEY-MELT)

Yonsei University Health System (YUHS)

Status and phase: Not yet enrolling; Phase 2

Conditions: Triple-Negative Breast Neoplasm

Treatments: Radiation: Partial breast-irradiation

Study type: Interventional

Funder types: Other

Identifiers

NCT07011823

3-2025-0070

Details and patient eligibility

About

A single-arm, single-institution study to induce phenotypic changes in the tumor microenvironment by delivering 8Gy partial breast irradiation in immune-cold triple-negative breast cancer confirmed by PD-L1 and TILs. Additional tissue biopsy will be performed following radiation therapy. Subsequently, neoadjuvant chemotherapy including Pembrolizumab will be administered to evaluate whether pathological complete response rates are improved.

Full description

A single-arm, single-institution study to induce phenotypic changes in the tumor microenvironment by delivering 8Gy partial breast irradiation in immune-cold triple-negative breast cancer confirmed by PD-L1 and TILs. Additional tissue biopsy will be performed following radiation therapy.

Subsequently, under the supervision and management of breast surgery and medical oncology research teams, standard neoadjuvant chemotherapy for triple-negative breast cancer including pembrolizumab, paclitaxel, carboplatin, doxorubicin, and cyclophosphamide (KeyNote-522 regimen) will be administered, followed by surgical treatment.

Pathological complete response status in surgical specimens will be confirmed and reported by the pathologist.

Pathological examination and spatial multiplex analysis will be performed on biopsy and surgical specimens to explore biomarkers with significant changes.

As secondary end-points, disease-free survival and overall survival will be assessed.

Enrollment: 20 estimated patients

Sex: Female

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Breast cancer patients aged 20 years or older with clinical stage IIA or higher on imaging studies
• Patients with triple-negative breast cancer confirmed on tissue biopsy
• Cold immune tumor environment with tumor-infiltrating lymphocytes (TILs) <30% and PD-L1 Combined Positive Score (CPS) <10 on immunohistochemical staining of biopsy specimens
• Patients with no prior history of breast cancer
• Patients with no prior history of chemotherapy or radiation therapy
• Patients scheduled to receive partial breast irradiation
• Patients with ECOG performance status of 0-2
• Patients who voluntarily signed the informed consent form for study participation

Exclusion criteria

• Patients with non-triple-negative breast cancer on tissue biopsy
• Patients scheduled for surgery without neoadjuvant chemotherapy
• Patients with TILs ≥30% or PD-L1 CPS ≥10 on immunohistochemical staining of biopsy specimens (immune-hot tumor)
• Patients with recurrent breast cancer or de novo stage IV disease
• Patients who have previously received chemotherapy and/or radiation therapy to the ipsilateral breast and chest prior to study participation
• Patients unable to receive neoadjuvant chemotherapy and Pembrolizumab
• Vulnerable research subjects who are unable to participate voluntarily in the study due to physical/mental disabilities

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

20 participants in 1 patient group

Immunochemotherapy including pembrolizumab after partial breast-irradiation

Experimental group

Description:

First, 8Gy partial breast irradiation will be delivered in immune-cold triple-negative breast cancer (TNBC) confirmed by PD-L1 and TILs. Sequentially, standard neoadjuvant chemotherapy for triple-negative breast cancer including pembrolizumab, paclitaxel, carboplatin, doxorubicin, and cyclophosphamide (KeyNote-522 regimen) will be administered, followed by surgical treatment.

Treatment:

Radiation: Partial breast-irradiation