A Prospective, Single-center, Phase II Study of Sacituzumab Tirumotecan in Combination With Pembrolizumab for Neoadjuvant Treatment of Triple-Negative Breast Cancer (TNBC)
1. Histologically or cytologically confirmed stage II-III (T1cN1-2 or T2-4N0-2) triple-negative breast cancer (TNBC), defined as:
* Immunohistochemistry (IHC) showing ER and PR \<1%
* HER2-negative per 2028 ASCO-CAP guidelines (IHC 0/1+ or IHC 2+/ISH-)
2. Available tumor tissue sample for biomarker analysis.
3. At least one measurable lesion as per RECIST 1.1 criteria.
4. ECOG performance status 0-1.
5. Adequate organ function as evidenced by:
* Absolute neutrophil count ≥1.5×10⁹/L (no G-CSF support within 14 days)
* Platelets ≥100×10⁹/L (no transfusion within 14 days)
* Hemoglobin \>9 g/dL (no transfusion/ESA within 14 days)
* Total bilirubin ≤1.5×ULN
* AST/ALT ≤1.5×ULN
* Alkaline phosphatase ≤2.5×ULN
* Serum creatinine ≤1.5×ULN or CrCl ≥60 mL/min (Cockcroft-Gault)
* INR/PT ≤1.5×ULN
* TSH within normal range (or normal FT3/FT4 if TSH abnormal)
* Normal cardiac enzymes (isolated abnormalities allowed if clinically insignificant)
6. No prior anti-cancer therapy for current diagnosis.
7. For women of childbearing potential and men with WOCBP partners: agreement to use effective contraception from screening until 6 months post-treatment.
8. Willing and able to comply with study procedures and provide written informed consent.
You may not be if
1. LVEF \<50% by ECHO/MUGA or significant cardiac disease (NYHA Class III/IV).
2. Prior chemotherapy, targeted therapy, or radiotherapy for current breast cancer.
3. Previous treatment with immune checkpoint inhibitors (anti-PD-1/L1, anti-CTLA-4) or T-cell targeting therapies.
4. Prior Trop-2 directed therapy or topoisomerase I inhibitor treatment.
5. Other malignancies within 5 years (except adequately treated CIS of cervix, BCC, or cutaneous SCC).
6. Severe ocular surface disease (dry eye syndrome, meibomian gland dysfunction, or corneal disorders impairing healing).
7. Known hypersensitivity to study drug components.
8. History of immunodeficiency disorders or organ transplantation.
9. Current or history of:
* Steroid-requiring interstitial lung disease/pneumoniti Unresolved ILD/pneumonitis on screening imaging
11. Active infection requiring systemic therapy within 14 days prior to initiation.
12. Uncontrolled comorbidities that may:
* Compromise patient safety
* Interfere with study completion
13. Any condition that in the investigator's judgment may:
* Affect study drug evaluation
* Compromise safety assessments
* Interfere with data interpretation
* Otherwise contraindicate participation
Clareo Health | A Prospective, Single-center, Phase II Study of Sacituzumab Tirumotecan in Combination With Pembrolizumab for Neoadjuvant Treatment of Triple-Negative Breast Cancer (TNBC)
