SKB264 +/- KL-A167 in Recurrent or Metastatic HER2-negative Breast Cancer

This is an interventional treatment trial for Triple-negative Breast Cancer and HR+/HER2- BC Read More

Inclusion Criteria:

1. Males or females aged ≥ 18 and ≤ 75 years at the time of signing the informed consent form (ICF);
2. Histological and/or cytological diagnosis of TNBC based on pathology reports on recent biopsy samples or other pathological samples (central laboratory confirmation is not required)；
3. No prior systemic anti-tumor therapy for the recurrent and metastatic TNBC; the time interval of at least 6 months from the end of radiotherapy to enrollment for patients who have received prior radiotherapy for curative purposes; and patients who have received prior adjuvant or neoadjuvant chemotherapy progressed ≥ 12 months after completion of treatment are allowed to be included in this study.
4. Ability to provide fresh or archival tumor tissue for biomarker testing and analysis;
5. Patients with at least one measurable lesion per RECIST v1.1 criteria, and patients with only skin or bone lesions cannot be enrolled;
6. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 with an expected survival of ≥ 12 weeks;
7. Adequate organ and bone marrow function;
8. Patients must recover from all toxicities (recovery to ≤ Grade 1 based on CTCAE v5.0 assessment, or meeting the inclusion criteria in the protocol) due to prior treatment, with the exception of alopecia and vitiligo;
9. For female patients of childbearing age and male patients with partners of childbearing age, they have to use effective medical contraception during the study treatment period and for 6 months after the last dose of study medication (see Annex for specific contraceptive measures);
10. The patients voluntarily participate in the study, sign the informed consent form, and will be able to comply with the protocol-specified visits and relevant procedures.

Exclusion Criteria:

1. History of other malignancies, except locally recurring cancers that have undergone curative treatment, such as resected basal or squamous cell skin cancer, or carcinoma in situ of the cervix, or other solid tumors curatively treated with no evidence of disease for 5 years;
2. Patients with a history of central nervous system (CNS) metastases or current CNS metastases.
3. Imaging (CT or MRI) shows that the tumor has invaded large blood vessels or the investigator judges that the tumor is likely to invade important blood vessels and cause fatal hemorrhage during the follow-up study；
4. Received any systemic immune-stimulatory agents (including but not limited to interferons or interleukin IL-2, Including immune-stimulatory agents in clinical studies) within 4 weeks prior to the first dose of study; Received any traditional Chinese medicine for approved anti-tumor indications within 2 weeks prior to the first dose of study;
5. Received other clinical investigational drugs within 4 weeks or major surgery within 4 weeks prior to the first dose of the study treatment;
6. Patients who required the use of strong inhibitors or inducers of cytochrome P450 3A4 enzyme (CYP3A4) within 2 weeks prior to the first dose of the study treatment and during the study (strong inhibitors or inducers of CYP3A4 are not allowed in this study, and representative drugs for strong CYP3A4 inhibitors or inducers are listed in the annex);
7. Patients who required systemic corticosteroids (> 10 mg/day prednisone or equivalent; low-dose corticosteroids are allowed, such as ≤10 mg/day prednisone or equivalent, if the dose is stable for 4 weeks), or other immunosuppressive therapy within 2 weeks prior to the first dose. Steroids are allowed as prophylaxis for hypersensitivity reactions;
8. Patients who occurred arteriovenous thrombosis within 6 months prior to the first dose of study treatment，Such as cerebrovascular accidents (including temporary ischemic attacks), deep vein thrombosis (except for venous thrombosis caused by intravenous catheterization due to pre-chemotherapy), and pulmonary embolism, etc.
9. Patients who have received prior immune checkpoint inhibitors and TROP2-targeted therapies;
10. Serious or uncontrolled cardiac disease or clinical symptoms requiring treatment；
11. Patients with (noninfectious) interstitial lung disease (ILD) or history of pneumonia requiring steroid therapy; patients with serious pulmonary function impairment due to lung disease;
12. Uncontrolled systemic disease as judged by the investigator, included uncontrolled hypertension, uncontrolled diabetes, pesence of pleural effusion, pericardial effusion, or ascites that is clinically symptomatic or requires repeated drainage;
13. Active autoimmune disease requiring systemic treatment within the past 2 years (Hormone replacement therapy is not considered a systemic therapy, such as type I diabetes mellitus, hypothyroidism requiring only thyroxine replacement therapy, adrenal or pituitary insufficiency requiring only physiologic doses of glucocorticoid replacement therapy);
14. Active hepatitis B (hepatitis B surface antigen positive, and HBV-DNA ≥ 500 IU/ml or ULN, whichever is higher) or hepatitis C (hepatitis C antibody positive, and HCV-RNA above ULN); known history of positive human immunodeficiency virus (HIV) test or known acquired immunodeficiency syndrome (AIDS); positive syphilis antibody test;
15. Known hypersensitivity to the study drug or any of its components, or severe allergic reactions to other monoclonal antibodies;
16. Pregnant or lactating women;
17. Any patient whose condition deteriorates rapidly during the screening process prior to the first dose, such as severe changes in performance status, unstable pain requiring adjustment of analgesic therapy, etc;
18. Other circumstances that, in the opinion of the investigator, are not appropriate for participation in this study.