Clinical trial NCT07011823: Immune-checkpoint Blockade After Partial Breast Irradiation by Pembrolizumab in Early TNBC
Official title: Phase II Trial of Immunochemotherapy and Partial Breast Irradiation in Early TNBC With Immune-cold Tumor Environment (KEY-MELT)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Triple-Negative Breast Neoplasm
Keywords: Immune-cold microenvironment
Triple-negative breast cancer
Partial Breast Irradiation
Pembrolizumab
KeyNote-522
Immunochemotherapy
Lead sponsor: Gangnam Severance Hospital
Sponsor class: OTHER
First posted: 2025-06-10
Enrollment: 20
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Pathologic complete response
timeFrame: Within 3 weeks after surgical treatment
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: M.D.,Ph.D.
name: Sung Gwe Ahn
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.