Immune-checkpoint Blockade After Partial Breast Irradiation by Pembrolizumab in Early TNBC

NCT ID: NCT07011823

Last Updated: 2025-06-10

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-16
• Study Completion Date: 2033-07-31

Brief Summary

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.

Detailed 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.

Conditions

Triple-Negative Breast Neoplasm

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Immunochemotherapy including pembrolizumab after partial breast-irradiation

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.

Group Type: EXPERIMENTAL

Partial breast-irradiation

Intervention Type: RADIATION

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.

Interventions

Partial breast-irradiation

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.

Intervention Type: RADIATION

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Gangnam Severance Hospital

OTHER

Sponsor Role: lead

Responsible Party

Sung Gwe Ahn

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sung Gwe Ahn

Role: PRINCIPAL_INVESTIGATOR

M.D.,Ph.D.

Central Contacts

Sung Gwe Ahn, M.D.,Ph.D.

Role: CONTACT

asg2004@yuhs.ac

+82220193370

Soong June Bae, M.D.,Ph.D.

Role: CONTACT

mission815815@yuhs.ac

References

Schmid P, Cortes J, Dent R, McArthur H, Pusztai L, Kummel S, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Im SA, Untch M, Fasching PA, Mouret-Reynier MA, Foukakis T, Ferreira M, Cardoso F, Zhou X, Karantza V, Tryfonidis K, Aktan G, O'Shaughnessy J; KEYNOTE-522 Investigators. Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer. N Engl J Med. 2024 Nov 28;391(21):1981-1991. doi: 10.1056/NEJMoa2409932. Epub 2024 Sep 15.

Reference Type: BACKGROUND

PMID: 39282906 (View on PubMed)

Other Identifiers

3-2025-0070

Identifier Type: -

Identifier Source: org_study_id