9MW2821 + Toripalimab vs 9MW2821 for 1st Line Locally Advanced or Metastatic Urothelial Carcinoma

A Randomized Phase II Trial to Evaluate 9MW2821 in Combination With Toripalimab Compared With 9MW2821 Monotherapy for the 1st Line Treatment of Locally Advanced or Metastatic Urothelial Carcinoma

This study will compare the efficacy of 9MW2821+toripalimab versus 9MW2821 monotherapy in locally advanced or metastatic urothelial carcinoma patients who have not received any systemic treatment in the metastatic or advanced setting.

Inclusion Criteria:

• Voluntary participation
• Age 18-80
• ECOG 0-1
• Histologically confirmed inoperable locally advanced or metastatic urothelial carcinoma (including bladder, renal pelvis and ureter). Mixed histology with squamous or adenomatous differentiation is allowed if urothelial carcinoma differentiation is >50%.
• Has not received any systemic treatment for locally advanced or metastatic urothelial carcinoma
• At least 1 measurable target lesion that satisfies RECIST v1.1 definition. If the patient has received radiotherapy, the target lesion needs to be outside the radiation field or has demonstrated clear progression after radiotherapy.
• Life expectancy over 12 weeks
• Appropriate hematological and organ functions
• Agree to contraceptive measures until 180 days after the last dose of study drug administration
• Able to understand and follow study visits, treatment, laboratory assessment and other procedures

Exclusion Criteria:

• Other concurrent malignancy within 3 years prior to randomization
• Active autoimmune disease requiring systemic treatment within 2 years prior to randomization. Having received high dose corticosteroid (>10mg/day prednisolone equivalent) or other immunosuppressive agents.
• Severe cardiovascular or cerebral vascular thrombo-embolic events within 6 months prior to randomization
• Major surgery within 28 days prior to randomization, except for minor procedures that the PI considers not to impact study participation. Live vaccine within 28 days prior to randomization or planning to take live vaccine during the study. Radiotherapy or bladder infusion therapy within 21 days prior to randomization. Use of strong CYP3A4 inhibitors within 14 days prior to randomization.
• Lung effusion or ascites that require treatment within 14 days prior to randomization. Cancer-related severe uncontrolled bone pain or spinal cord compression within 14 days prior to randomization. Active infection that requires systemic antibiotic treatment within 7 days prior to randomization.
• Have received prior treatment with anti-PD-1, anti-PD-L1/PD-L2 or anti-CTLA-4 therapies. Have received prior treatment with Nectin-4 targeted therapy or ADC with MMAE as payload. Have received allogeneic hematological stem cell transplantation or solid organ transplant.
• Toxicities from previous cancer treatment (radiotherapy, chemotherapy or surgery) that have not recovered to grade 0-1 according to CTCAE v5.0, except for alopecia and skin hyperpigmentation.
• Severe dry eyes, active keratitis, corneal ulceration or other risk factors for corneal diseases where the PI judges to be not suited for this study
• Preexisting grade ≥ 2 neuropathy prior to randomization
• Other uncontrolled serious illness
• Brain metastasis or meningeal carcinomatosis
• HBsAg positive, and HBV-DNA copy number positive ; HCV-Ab positive and HCV-RNA positive; HIV-Ab positive
• Known allergy to the study drug or components of the study drug
• Drug abuse or psychiatric disorder that would impact study compliance
• Other circumstances that the PI judges to be not suitable for the study