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

A Randomized, Controlled, Open-Label, Multicenter Phase 3 Trial of SYS6002 Versus Investigator's Choice Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Carcinoma After Failure of Platinum-based Chemotherapy andPD-(L)1 Inhibitors

This study is a randomized, controlled, open-label, multicenter phase III clinical trial, which aims to evaluate the efficacy,safety PK characteristics, and immunogenicity of SYS6002 compared with chemotherapy in participants with locally advanced or metastatic urothelial carcinoma.

This study has not yet been submitted for ethical review. The current registration is a pre-registration. Recruitment will commence only after formal approval is obtained from the relevant Ethics Committee).

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:

  1. History of severe cardiovascular disease within 6 months prior to randomization, including but not limited to:

     1. 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);
     2. With history of myocardial infarction, unstable angina pectoris, angioplasty and coronary artery bypass surgery;
     3. 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;
     4. Ischemic or Hemorrhagic Stroke;
     5. Pulmonary Embolism Accident;

  2. Other clinically significant diseases:

     1. HbA1c > 8%;
     2. Participants with active keratitis and corneal ulcer, or fundus lesions with a risk of blindness;
     3. Grade ≥2 neuropathy prior to randomization;
     4. 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;
     5. Active HBV or HCV infection;
     6. History of immunodeficiency (HIV-positive, acquired or congenital immunodeficiency, etc.), or organ transplantation;
     7. History of another malignancy within 3 years prior to randomization;
     8. 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;
     9. 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.