SYS6002 vs PADCEV in Patients With Advanced Urothelial Carcinoma

Inclusion criteria

• 1. Patients aged 18-80 years (inclusive);
• 2. Pathologically confirmed patients with advanced urothelial carcinoma who have received a platinum-based chemotherapy with anti-PD-(L)1 agent. For those who received these therapies in the adjuvant or neoadjuvant setting, disease progression must have occurred during treatment or within 12 months of treatment completion;
• 3 An archival tumor tissue sample or a fresh tissue sample should be provided;
• 4 Subjects must have measurable disease according to RECIST (version 1.1);
• 5 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• 6 Life expectancy of ≥ 3 months;
• 7 Major organ function must meet the relevant laboratory test standards for hematology, renal function, liver function, and coagulation within 7 days prior to treatment;
• 8Sexually active fertile subjects must agree to use methods of contraception during the study and at least 7 months after termination of study therapy and have a negative urine or serum pregnancy test within 7 days prior to randomization;
• 9.Willing to participate in the study, understand the study procedures, and sign a written informed consent form.

Exclusion criteria

• 1.Active central nervous system metastases or leptomeningeal metastasis;
• 2.Adverse events from prior anti-tumor therapy not recovered to ≤ Grade 1 (unless the investigator deems there is no safety risk)；
• 3.Any serious and/or uncontrolled concurrent illness that may interfere with patient's participation in the study:

• Participants with a history of severe cardiovascular disease within 6 months prior to randomization, including but not limited to:

Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia and third-degree atrioventricular block requiring clinical intervention; corrected QT interval > 480 ms by Fridericia method (Fridericia formula: QTcF = QT/RR^0.33, RR = 60/heart rate); With history of myocardial infarction, unstable angina pectoris, angioplasty and coronary artery bypass surgery; New York Heart Association (NYHA) classification Grade III and above heart failure, and left ventricular ejection fraction (LVEF) < 50% in the tests and examinations during the screening period; cerebrovascular accidents; pulmonary embolisms;

• Other clinically significant diseases:

HbA1c > 8%; Participants with active keratitis and corneal ulcer, or fundus lesions with a risk of blindness; Grade ≥2 neuropathy prior to randomization; Severe infection within 4 weeks prior to randomization; active infection requiring systemic antibiotics, antiviral, or antifungal therapy within 2 weeks prior to randomization; Active HBV or HCV infection; History of immunodeficiency (HIV-positive, acquired or congenital immunodeficiency, etc.), or organ transplantation; History of another malignancy within 3 years prior to randomization; History of interstitial lung disease (ILD) / non-infectious pneumonia, or current ILD/non-infectious pneumonia, or imaging findings at screening that cannot rule out these conditions, except for those who are determined to be risk-free after discussion between the investigator and the sponsor; Pleural effusion, ascites or pericardial effusion with symptoms or requiring puncture or drainage within 2 weeks prior to randomization;

• 4.Use of other unmarketed clinical investigational drugs or treatments, chemotherapy, radiotherapy targeted therapy within 4 weeks prior to randomization; use of traditional Chinese medicine with anticancer indication, oral fluoropyrimidine drugs, small molecule targeted drug within 2 weeks prior to randomization; use of palliative radiation or local therapy within 2 weeks prior to randomization;with major surgery within 4 weeks prior to randomization;
• 5.Allergy to any component of SYS6002, or humanized monoclonal antibodies; investigator-determined ineligibility for enfortumab vedotin therapy.
• 6. Other conditions deemed by the investigator as unsuitable for participation in this clinical trial.