A Prospective, Single-center, Phase II Study of Sacituzumab Tirumotecan in Combination With Pembrolizumab for Neoadjuvant Treatment of Triple-Negative Breast Cancer (TNBC)

Korábbi kezelés

• Prior chemotherapy, targeted therapy, or radiotherapy for current breast cancer.
• Previous treatment with immune checkpoint inhibitors (anti-PD-1/L1, anti-CTLA-4) or T-cell targeting therapies.
• Prior Trop-2 directed therapy or topoisomerase I inhibitor treatment.
• Current or history of:
  • Steroid-requiring interstitial lung disease/pneumoniti Unresolved ILD/pneumonitis on screening imaging
  • Clinically significant pulmonary conditions including:
  • Recent pulmonary embolism (≤3 months)
  • Severe asthma/COPD/restrictive lung disease
  • Pleural effusion requiring intervention
  • Connective tissue disease with pulmonary involvement
  • Prior pneumonectomy
• Active infection requiring systemic therapy within 14 days prior to initiation.

Más betegség

• Other malignancies within 5 years (except adequately treated CIS of cervix, BCC, or cutaneous SCC).
• Severe ocular surface disease (dry eye syndrome, meibomian gland dysfunction, or corneal disorders impairing healing).
• Known hypersensitivity to study drug components.
• History of immunodeficiency disorders or organ transplantation.
• Active autoimmune disease requiring systemic treatment (past 2 years), except:
  • Hormone replacement therapy
  • Physiologic corticosteroid replacement
• Any condition that in the investigator's judgment may:
  • Affect study drug evaluation
  • Compromise safety assessments
  • Interfere with data interpretation
  • Otherwise contraindicate participation

Laborértékek

• LVEF <50% by ECHO/MUGA or significant cardiac disease (NYHA Class III/IV).

Egyéb

• Uncontrolled comorbidities that may:
  • Compromise patient safety
  • Interfere with study completion

• 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-)
• Available tumor tissue sample for biomarker analysis.
• At least one measurable lesion as per RECIST 1.1 criteria.
• ECOG performance status 0-1.
• 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)
• No prior anti-cancer therapy for current diagnosis.
• For women of childbearing potential and men with WOCBP partners: agreement to use effective contraception from screening until 6 months post-treatment.
• Willing and able to comply with study procedures and provide written informed consent.