9MW2821 Combined With Toripalimab in Perioperative Patients With Urothelial Cancer

• 9MW2821 (Drug): 9MW2821, 1.25mg/kg, intravenous (IV) infusion
• Toripalimab Injection (Drug): Toripalimab, 240mg, intravenous (IV) infusion

Primary outcomes

• pCR (Arm 1 and 2) [Up to 24 months]: Pathological complete response
• cCR (Arm 3) [Up to 24 months]: Clinical complete response

Secondary outcomes

• cORR [Up to 24 months]: Clinical objective response rate
• Pathological downstaging rate (Arm 1 and 2) [Up to 24 months]
• DFS (Arm 1 and 2) [Up to 24 months]: Disease-free survival
• Duration of clinical complete response (Arm 3) [Up to 24 months]
• PFS (Arm 3) [Up to 24 months]: Progression-free survival
• OS [Up to 24 months]: Overall Survival
• AE/SAE [Up to 24 months]: Adverse event, serious adverse event
• Immunogenicity [Up to 24 months]: Anti-Drug Antibody (ADA) of 9MW2821
• Nectin-4 and PD-L1 expression [Up to 24 months]

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Sign the informed consent form approved by IEC.
* Male or female subjects aged ≥18 years old.
* ECOG status: 0 or 1.
* Histologically confirmed urothelial cancer.
* Imaging confirmed non-metastatic urothelial cancer (M0). Arm 1: MIBC, T2-4aN0-1. Arm 2: High-risk UTUC, N0. Arm 3: MIBC, T2-4aN0.
* Adequate tumor tissues submitted for test.
* Life expectancy for more than 12 weeks.
* Adequate organ functions.
* Proper contraception methods.
* Willingness to follow the study procedures.

Exclusion Criteria:

* Prior systemic anti-tumor therapy for urothelial cancer.
* Previously treated with PD-1/PD-L1 inhibitors or antibody-drug conjugates (ADCs).
* History of another malignancy within 3 years.
* History of autoimmune disease requiring systemic treatment within 2 years.
* History of clinically significant cardiac/cerebrovascular diseases or thrombosis within 1 year.
* Major surgery treated within 28 days; Cystoscopy/ureteroscopy biopsy or intravesical instillation therapy within 7 days.
* Peripheral neuropathy Grade ≥ 2.
* Any situations adding the risk of severe dry eye, active keratitis or corneal ulcer, etc.
* Active HBV/HCV/HIV infection, etc.
* Any other serious chronic or uncontrolled disease.
* Any live vaccines got within 28 days.
* Organ transplantation or allogeneic hematopoietic stem cell transplantation in the past.
* Any potent CYP3A4 inducers/inhibitors taken within 14 days.
* Known allergic sensitivity to any of the ingredients of the study drug.
* History of drug abuse or mental illness.
* Other conditions unsuitable into the study.