SYS6002 vs Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Carcinoma

Inclusion criteria

• 1.Participantss aged 18-75 years (inclusive);
• 2. Pathologically confirmed patients with locally advanced or metastatic urothelial carcinoma
• 3 Participants havefailed of platinum-based chemotherapy and PD-(L)1 inhibitors; for participants who received platinum-based chemotherapy and PD-(L)1 inhibitors in the adjuvant/neoadjuvant setting, disease recurrence or progression must have occurred within 12 months after completion of that therapy; radiographically confirmed disease progression during or after the most recent treatment regimen;
• 4 Participants 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 Adequate major organ function (hematology, renal, liver, and coagulation) as determined by laboratory tests performed within 7 days prior to treatment;
• 8 Sexually active fertile participants must agree to use methods of contraception during the study and at least 6 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. Prior Nectin-4-targeted therapy;
• 3. Adverse events from prior antitumor therapy not recovered to Grade ≤ 1 per NCI-CTCAE v5.0；
• 4. Any serious and/or uncontrolled concurrent illness that may interfere with patient's participation in the study:

• 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;
• Ischemic or Hemorrhagic Stroke;
• Pulmonary Embolism Accident;
• 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 of Grade ≥2 (CTCAE v5.0) requiring systemic antibiotics, antivirals, or antifungals 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 condition, 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 syptoms or requiring puncture or drainage within 2 weeks prior to randomization;
• 5. Use of other unmarketed clinical investigational drugs or treatments, chemotherapy, radiotherapy, or 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; or major surgery within 4 weeks prior to randomization;
• 6. Allergy to any component of SYS6002 or to humanized monoclonal antibodies;
• 7. Other conditions deemed by the investigator as unsuitable for participation in this clinical trial.