Breast cancer
Conditions
Interventions
Study group:Sacituzumab Tirumotecan 4mg/kg in Combination with Bevacizumab 5mg/kg Q2W, until disease progression or intolerant toxicity,
Sponsors
Sun Yat-sen University Cancer Center
Eligibility
Sex/Gender
Female
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Female patients aged =18 years with histologically confirmed metastatic or locally advanced unresectable breast cancer; 2. Disease progression after standard therapy: patients with hormone receptor-positive, HER2-negative disease must have failed endocrine therapy; patients with hormone receptor-negative, HER2-negative disease must have progressed after at least one line of chemotherapy; 3. HER2-negative defined as: immunohistochemistry (IHC) 0 or 1+, or IHC 2+ with negative HER2 gene amplification by fluorescence in situ hybridization (FISH); in cases of multiple specimen tests, the most recent result shall be used; 4. Availability of tumor tissue (formalin-fixed, paraffin-embedded or freshly processed recurrent tumor tissue) for TROP2 expression assessment; 5. Presence of measurable central nervous system (CNS) disease, defined as at least one brain parenchymal lesion (maximum diameter >=1 cm) that can be precisely measured in at least one dimension by local radiologic imaging; absence of CNS symptoms or symptoms that are well controlled, with no immediate need for radiotherapy; 6. Prior receipt of radiotherapy and/or chemotherapy during neoadjuvant or adjuvant settings is permitted; 7. At least one measurable lesion; 8. ECOG performance status: 0–1; 9. Expected survival >=12 weeks; 10. Adequate organ function as defined below: (1) Hematologic parameters: ANC >= 1.5×10^9/L, PLT >= 75×10^9/L, Hb >= 85 g/L (no blood or blood product transfusion or use of G-CSF or other hematopoietic growth factors within 14 days prior to screening); (2) Biochemical parameters: TBIL = 50 mL/min (Cockcroft-Gault formula); 11. Women of childbearing potential must have adopted reliable contraception, or have a negative serum or urine pregnancy test within 7 days prior to enrollment, and must agree to use appropriate contraceptive methods throughout the trial and for 8 weeks after the last dose of study drug; 12. Informed consent obtained from the subject, with good compliance and ability to adhere to follow-up requirements.
Exclusion criteria
Exclusion criteria: 1. Patients with extensive leptomeningeal metastasis who have inadequate response to dehydration therapy (e.g., corticosteroids) or require urgent radiotherapy; 2. Symptomatic active brain metastases requiring urgent cranial radiotherapy (asymptomatic CNS metastases are permitted); 3. Disease progression following whole-brain radiotherapy or stereotactic conformal radiotherapy to all intracranial lesions; 4. Patients with untreated spinal cord compression or active CNS metastases, except those who have been stabilized for >=1 month after treatment and have discontinued corticosteroids for >2 weeks; 5. History of grade 3–4 hypersensitivity reactions to bevacizumab or trastuzumab deruxtecan; prior treatment with other anti-angiogenic agents (e.g., tyrosine kinase inhibitors such as apatinib or anlotinib) is permitted; 6. Prior receipt of two or more antibody-drug conjugates; 7. Poorly controlled hypertension; or history of hypertensive crisis or hypertensive encephalopathy; 8. History of grade =2 CNS hemorrhage within 12 months prior to enrollment; 9. HER2-positive defined as: IHC 3+ or IHC 2+ with HER2 gene amplification confirmed by FISH; patients with prior HER2-positive status but recent pathology confirming HER2-negative status are permitted; 10. History of clinically significant cardiovascular, hepatic, respiratory, renal, hematologic/endocrine, or neuropsychiatric disorders; 11. Active acute or chronic hepatitis B (defined as HBsAg-positive or anti-HBc-positive with HBV DNA >=1×10^3 copies/mL or >=200 IU/mL) or active acute or chronic hepatitis C (anti-HCV-positive); patients with anti-HCV-positive but HCV RNA-negative are permitted; 12. Prior receipt of other anti-tumor therapy with unresolved adverse events/reactions graded >1; 13. Known or suspected interstitial lung disease; presence of any moderate-to-severe pulmonary disease within 3 months prior to first dose that may interfere with detection or management of drug-related pulmonary toxicity, including but not limited to: idiopathic pulmonary fibrosis, organizing pneumonia/bronchiolitis obliterans, pulmonary embolism, severe asthma, severe COPD, obstructive/restrictive lung disease; any autoimmune, connective tissue, or inflammatory disease involving the lungs (e.g., rheumatoid arthritis, Sjögren’s syndrome, sarcoidosis); or prior pneumonectomy; patients who experienced =grade 3 interstitial lung disease during prior immune checkpoint inhibitor therapy are excluded; 14. Known inherited or acquired bleeding diathesis (e.g., hemophilia, coagulopathy); 15. History, disease evidence, treatment, or laboratory abnormalities that may interfere with trial outcomes or impede full participation, or other conditions deemed unsuitable by the investigator; 16. Any severe underlying disease, comorbidity, or active infection; 17. Concurrent receipt of other anti-tumor therapies; 18. History of epilepsy or status epilepticus; 19. Pregnant or lactating women; 20. Poor compliance or inability to undergo scheduled follow-up; 21. Known hypersensitivity to study drug; 22. History of other malignancies within 3 years, excluding: surgically resected non-melanoma skin cancer, adequately treated cervical carcinoma in situ, locally curative-treated prostate cancer, surgically curative-treated ductal carcinoma in situ, or any other malignancy diagnosed >=2 years prior with no evidence of disease and no treatment within 2 years prior to randomization; 23. Any
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-Free Survival;Overall Survival;Quality of Life; | — |
Countries
China
Contacts
Public ContactHuang Jiajia, Wang Shusen
Sun Yat-sen University Cancer Center
Outcome results
None listed