Sequencing SG vs. T-DXd in HER2-Low/TROP2-High Metastatic Breast Cancer

Korábbi kezelés

• Prior treatment with sacituzumab govitecan, trastuzumab deruxtecan, or any other drug targeting the same molecular pathway.
• History of another primary malignancy, except for:
  • Malignancy treated with curative intent with no evidence of active disease for ≥2 years prior to study intervention and with low risk of recurrence, or
  • Adequately treated carcinoma in situ of the cervix, stage I endometrioid carcinoma of the uterus, or non-melanoma skin cancer (e.g., basal cell carcinoma or squamous cell carcinoma).
• Participation in another investigational drug trial within 4 weeks prior to the first study treatment (observational studies are permitted) or major surgery within 4 weeks prior to the first study treatment.
• Prior anticancer therapy within specified timeframes:
  • Chemotherapy, radiotherapy, targeted therapy, or immunotherapy within 4 weeks before the first study treatment,
  • Anticancer endocrine therapy or traditional Chinese medicine with antitumor intent within 2 weeks before the first study treatment.
• Primary central nervous system (CNS) tumor or untreated/symptomatic CNS metastases. Patients with asymptomatic, stable CNS metastases not requiring steroids or specific CNS-directed therapy for at least 4 weeks prior to screening may be eligible.

Más betegség

• Contraindication or known hypersensitivity to sacituzumab govitecan, trastuzumab deruxtecan, or any of their components (including topoisomerase I inhibitors).
• Active infection or uncontrolled systemic disease, including but not limited to:
  • Active HIV, HBV, or HCV infection,
  • Active autoimmune disease,
  • Symptomatic pleural effusion, ascites, or pericardial effusion requiring drainage,
  • Severe or uncontrolled cardiac disease requiring treatment,
  • Poorly controlled diabetes or hypertension despite medical therapy.
• History of or current interstitial lung disease, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm, or other clinically significant pulmonary disorders.
• Known neurological or psychiatric disorders (e.g., epilepsy, dementia) or cognitive impairment that would compromise understanding of the study objectives, compliance, or ability to provide informed consent; or significant peripheral neuropathy.
• Any other condition deemed unsuitable for participation by the investigator.

Egyéb

• Patients meeting any of the following criteria will be excluded from the study:
• Pregnant or breastfeeding women, or women of childbearing potential with a positive pregnancy test at baseline; patients (male or female) who are unwilling to use effective contraception throughout the study period.

• Patients who meet all of the following criteria are eligible for inclusion in this study:
• Male or female, age ≥18 years.
• ECOG performance status ≤2, with an estimated life expectancy of >3 months.
• Histologically confirmed unresectable or metastatic breast cancer that is:HER2 IHC 1+ triple-negative breast cancer, or HR-positive/HER2-ultralow or HER2 IHC 1+ breast cancer.
• Planned to receive monotherapy with Sacituzumab Govitecan and Trastuzumab Deruxtecan.
• For triple-negative breast cancer: prior systemic therapy lines ≥1.
• For HR-positive/HER2-negative metastatic breast cancer: prior endocrine therapy is required. Prior chemotherapy, immunotherapy, or targeted therapy is allowed; 0-2 lines of chemotherapy in the advanced/metastatic setting are permitted.
• Prior treatment-related adverse events have recovered to ≤Grade 1 per NCI CTCAE v5.0 (except for alopecia, non-clinically significant or asymptomatic laboratory abnormalities).
• Presence of at least one measurable or evaluable lesion.
• Willingness to provide archival or fresh tumor tissue samples for multi-omics analysis, including:
  • Baseline prior to ADC1 treatment,
  • After 2 cycles of ADC1 therapy,
  • At progression on ADC1 therapy or baseline prior to ADC2 therapy,
  • At progression on ADC2 therapy.
• FFPE tissue blocks are preferred over unstained slides. Patients must consent to tumor biopsy; if tissue is unavailable, biopsy is not feasible, or the patient declines biopsy, eligibility may be discussed and approved by the investigator.
• No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50% within 28 days before treatment.
• Adequate organ function within 7 days prior to treatment initiation:
  • Bone marrow: absolute neutrophil count (ANC) ≥1.5 × 10⁹/L; platelet count ≥100 × 10⁹/L; hemoglobin ≥90 g/L (no transfusion or blood component use within 14 days before first dose; no growth factor support within 7 days before first dose).
  • Liver: total bilirubin ≤1.5 × ULN (or <3 × ULN if Gilbert's syndrome or documented liver metastases present); ALT and AST ≤2.5 × ULN (≤5 × ULN if liver metastases present).
  • Renal: serum creatinine ≤1.5 × ULN OR creatinine clearance ≥50 mL/min (calculated by Cockcroft-Gault formula).
  • Coagulation: INR ≤1.5 × ULN and aPTT ≤1.5 × ULN (unless therapeutically anticoagulated).
• Voluntarily signed informed consent form and willingness to comply with the study protocol.
• Willingness to provide complete clinical medical record data.