A Study of SKB518 in Patients With Advanced Solid Tumors

This is a first-in-human (FIH), phase 1, multicenter, open-label, dose-escalation study of SKB518 to evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity in adult subjects with advanced or metastatic solid tumor relapsed/refractory to standard therapies or for which no effective standard therapy is available. Dose escalation and de-escalation decisions are based on the mTPI-2 design and depend on the number of subjects enrolled and the number of DLTs observed at the current dose level.

Inclusion criteria

• Subject must be at least 18 years of age at the time of signing the informed consent;
• Histological or cytological diagnosis of solid tumor that is advanced/metastatic solid tumor by pathology report and have progressed on, have been intolerant to, or have been ineligible for standard of care treatments.
• Subjects able to provide tumor blocks or 8~10 slides [fresh paraffin-embedded tumor tissue or archived paraffin-embedded tumor tissue (maximum time limit is not more than 2 years)] before the first dose of study intervention for biomarkers testing.
• At least one measurable lesion can be accurately measured per RECIST v1.1 as determined by the local site investigator/radiology assessment. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Subjects with Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Life expectancy of at least 3 months as assessed by the investigators.
• Subjects with adequate organ and bone marrow function confirmed by laboratory results within 7 days prior to the first dose.
• Has recovered from all toxicities from previous therapy with the exception of stable, chronic (>3 months) toxicities not considered a safety risk (e.g. alopecia, vitiligo), after consultation with the Sponsor.
• Subjects of childbearing potential (male or female) must use effective medical contraception during the study until 6 months after the last dose.
• Subjects must be able to provide documented voluntary informed consent.

Exclusion criteria

• Has known active or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis are not eligible.
• Has a known additional malignancy that is progressing or has required active treatment within the past 5 years.
• Has a history of major cardiovascular, cerebrovascular or thromboembolic diseases.
• Has serious and/or uncontrolled concomitant diseases.
• Has known active tuberculosis.
• Has known human immunodeficiency virus (HIV) infection that is not well controlled.
• Has any active viral hepatitis, hepatitis B or hepatitis C.
• Has had major surgery within 28 days prior to the first dose.
• Has known allergy or hypersensitivity to SKB518, or the excipients of SKB518.
• Has a history of interstitial lung disease (ILD) or a history of non-infectious pneumonitis that required steroids.
• Clinically serious lung injuries caused by lung diseases.
• History of documented severe dry eye syndrome.
• Has a history of allogeneic tissue/solid organ transplant.
• Has known uncontrollable effusion.
• Subjects who are vaccinated with live vaccine within 30 days before the first dose, or plan to be vaccinated with live vaccine during the study period.
• Has received strong cytochrome P450 (CYP3A4) inhibitors or inducers, or has received BCRP inhibitors within 2 weeks prior to the first dose.
• Subjects who received any chemotherapy, radiotherapy, immunotherapy, or biologic therapy treatment within 4 weeks; or who received any small molecular tyrosine kinase inhibitor, antitumor hormonal therapy, system immune-stimulator, or therapy with traditional Chinese medicines approved for antitumor treatment, etc. within 2 weeks before the first dose.
• Has an active infection requiring systemic therapy.
• Subjects with the disease that requires systemic corticosteroid therapy (prednisolone or equivalent dose of similar drugs at a dose of >10 mg/d) or other immunosuppressive therapy within 14 days before the first dose.
• Is currently participating and receiving study therapy in a study of an investigational agent or has participated and received study therapy in a study of an investigational agent or has used an investigational device within 28 days of fist dose.
• Before the first dose, the subject's condition deteriorates rapidly.
• Has a known psychiatric or substance abuse disorders.
• The Investigator considers other situations that will interfere with the evaluation of the study intervention or the safety of the subjects or the interpretation of the results of the study.