A Study on the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of SKB500 in Subjects With Advanced Solid Tumors

This study is a multicenter, open-label Phase I clinical trial to evaluate the safety, tolerability, PK profile, immunogenicity, and antitumor activity of SKB500 in subjects with advanced solid tumors. The study includes a dose-escalation phase, a dose-expansion phase, and an indication-expansion phase.

Inclusion criteria

• Male or female participants between 18 and 75 years old.
• Histologically or cytologically confirmed advanced solid tumors for which standard treatment either does not exist or has proven ineffective or intolerable.
• Subjects should ideally provide a tumor tissue sample for biomarker testing during the screening period.
• Has at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
• ECOG performance status score of 0 or 1.
• Expected survival of at least 12 weeks.
• Has adequate hematopoietic, renal and hepatic functions.
• Have recovered to grade ≤ 1 of prior anti-cancer treatment toxicities.
• Male and female subjects must agree to use highly effective contraceptive methods throughout the study.
• Subjects must voluntarily enter the study, sign the informed consent form, and be able to comply with the visits and procedures.

Exclusion criteria

• Subjects with known active CNS metastases, carcinomatous meningitis, leptomeningeal metastases, or spinal cord compression.
• Subjects with other malignancies within 5 years before the first dose.
• Any severe and/or uncontrolled concurrent disease that may interfere with the subject's participation in the study.
• Active hepatitis B, or hepatitis C; active tuberculosis, or human immunodeficiency virus (HIV) test positive, or known acquired immunodeficiency syndrome (AIDS).
• History of allergy to any component of SKB500 or history of severe hypersensitivity reactions to other monoclonal antibodies.
• Subjects with a history of interstitial lung disease, non-infectious pneumonia, or other pulmonary diseases significantly affecting lung function.
• History of allogeneic organ transplantation or hematopoietic stem cell transplantation.
• Uncontrolled pleural effusion, ascites, or pericardial effusion.
• Have received ADCs with the same target or the same toxins.
• Have received chemotherapy, small molecule targeted therapy, and traditional Chinese medicine preparations within 14 days or 5 half-lives before the first dose; have received any immunotherapy, large molecule anticancer drug treatment, or more than 30% bone marrow radiation or extensive radiotherapy within 28 days before the first dose.
• Have undergone major surgery or severe trauma within 28 days before the first dose.
• Have received other clinical trial medications within 28 days before the first dose.
• Has previously received anti-cancer or live vaccines within 28 days before the first dose
• Have received systemic steroids or other immunosuppressive treatments within 14 days before the first dose.
• Have received potent CYP3A4 inhibitors, inducers, or BCRP inhibitors within 14 days or 5 half-lives before the first dose.
• Pregnant or lactating female.
• Any disease or condition that, in the investigator's opinion, would compromise subject safety or interfere with study assessments.