Study of SKB103 in HER2-negative Breast Cancer

A Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of SKB103 in Participants With Locally Advanced, Recurrent, or Metastatic HER2-negative Breast Cancer.

This is a Phase I/II clinical study to evaluate the safety and efficacy of SKB103 in participants with advanced (locally advanced, recurrent, or metastatic) HER2-negative breast cancer. The study includes a Phase 1 dose escalation stage and a Phase 2 indication expansion stage.

This is a multi-center, open-label, phase I/II clinical study to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and efficacy of SKB103 in participants with locally advanced, recurrent or metastatic HER2-negative breast cancer.

The study includes a Phase 1 dose escalation stage and a Phase 2 indication expansion stage.

Key Inclusion Criteria:

1. Willingness to participate in the study, sign the informed consent form(ICF), and comply with the protocol-specified visits and relevant procedures.
2. Aged ≥ 18 and ≤ 75 years at the time of signing ICF.
3. Histologically and/or cytologically confirmed HER2-negative Breast cancer who have failed standard therapy.
4. Participants should provide tumor tissue samples for biomarker testing as much as possible.
5. At least one measurable lesion per RECIST v1.1.
6. Eastern Cooperative Oncology Group (ECOG) score is 0 or 1.
7. Life expectancy ≥ 12 weeks.
8. Acceptable bone marrow and organ function.
9. Male and female participants must agree to use highly effective contraceptive methods during the study period.

Key Exclusion Criteria:

1. Participants with known meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, and active central nervous system (CNS) metastases.
2. Participants with other malignant tumors within 3 years prior to the first administration.
3. Presence of any serious cardiovascular and cerebrovascular diseases or cardiovascular and cerebrovascular risk factors.
4. Presence of any uncontrolled systemic disease, as judged by the investigator.
5. Presence of pleural effusion, pericardial effusion, or ascites with clinical symptoms or requiring repeated drainage.
6. History of interstitial lung disease or noninfectious pneumonitis.
7. Other lung diseases that may interfere with drug-related pulmonary toxicity or may cause clinically serious lung injuries.
8. Documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or history of corneal disorders that prevent/delay corneal healing.
9. Presence of risk of developing esophagotracheal fistula or esophageal pleural fistula, or tumor invasion or compression of surrounding vital organs and major blood vessels with related clinical symptoms.
10. Clinical symptoms of intestinal obstruction, gastrointestinal perforation or fistula, urethral fistula, and abdominal abscess within 3 months prior to the first administration.
11. Toxicities from prior anti-tumor therapy not recovering to ≤ Grade 1.
12. Has experienced immune-related adverse events (irAE) of Grade 3 or higher during prior immunotherapy
13. Serious infection occurred within 4 weeks prior to the first administration.
14. Active hepatitis B or hepatitis C.
15. Positive result of human immunodeficiency virus (HIV) test or history of acquired immunodeficiency syndrome (AIDS); Known active syphilis infection.
16. Known active pulmonary tuberculosis.
17. Known history of allogeneic organ transplantation or hematopoietic stem cell transplantation.
18. History of allergies to any component of SKB103 injection, or severe hypersensitivity reaction to other monoclonal antibodies.
19. Has received prior antibody or drug therapy targeting T-cell co-stimulatory or checkpoint pathways, or cell therapy.
20. Received chemotherapy, immunotherapy, biological therapy, or other large molecule anti-tumor drugs within 4 weeks prior to the first administration.
21. Has received radiation therapy to lung lesions with a total dose >30 Gy within 6 months prior to the first dose of study drug.
22. Participants who received major surgeries 4 weeks prior to the first administration.
23. Participants who received other investigational drugs within 4 weeks prior to their first administration.
24. Participants who have previously received anti-tumor vaccines or have received any live vaccines within 4 weeks prior to the first administration or scheduled to receive live vaccines during study treatment.
25. Receipt of systemic corticosteroid therapy (>10mg of prednisone or its equivalent) or other immunosuppressive agents within 2 weeks prior to the first dose.
26. Receipt of strong inhibitors or inducer of cytochrome P450（CYP3A4） or inhibitors of breast cancer resistance protein (BCRP) within 2 weeks prior to the first administration or within 5 half-lives of the known drugs(whichever is longer).
27. Pregnant or lactating women.
28. Known history of psychiatric disorder or substance abuse that may interfere with study compliance.
29. Has any local or systemic condition (non malignant or tumor related) that may impair protocol compliance.
30. Any condition that, in the opinion of the Investigator, may interfere with the evaluation of the study drug, participant safety, or interpretation of the study results; or any other condition that the investigator deems unsuitable for participation in this study.