Overview

This is a Phase 3, Open-Label, Multicenter, Randomised, Controlled Study designed to compare RC48-ADC in Combination With JS001 to Chemotherapy Alone in Previously Untreated HER2-Expressing Unresectable Locally Advanced or Metastatic Urothelial Carcinoma.

Eligibility

Inclusion Criteria:

• Expected survival ≥12 weeks.
• Locally advanced unresectable or metastatic UC with histopathological confirmation, including UC originating from the renal pelvis, ureters, bladder, or urethra.
• Participants must not have received prior systemic therapy for locally advanced or metastatic urothelial carcinoma with the following exceptions:

        Participants that received neoadjuvant chemotherapy with recurrence >6 months from
        completion of therapy are permitted; Participants that received adjuvant chemotherapy
        following cystectomy with recurrence >6 months from completion of therapy are permitted.
          -  At least one measurable lesion based on RECIST version 1.1
          -  HER2-expressing status determined by the central laboratory to be IHC 1+, 2+ or 3+.
          -  ECOG performance status score: 0 or 1.
          -  Adequate cardiac, bone marrow, hepatic, renal, and coagulation functions.
        Exclusion Criteria:
          -  Known hypersensitivity to RC48-ADC or Toripalimab or any of its components.
          -  History of major surgery within 4 weeks of planned start of trial treatment.
          -  Toxicity from a previous treatment has not returned to Grade 0-1.
          -  Prior ADCs or PD-1/PD-L1 inhibitor therapy.
          -  Active central nervous system (CNS) metastases.
          -  Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV)
             infection.
          -  History of other malignancy within the previous 5 years, except for low-risk localized
             prostate cancer, appropriately treated carcinoma in situ of the cervix, non-melanoma
             skin carcinoma, or cancers with a similar curative outcome as those mentioned above.
          -  Other serious, uncontrolled concomitant diseases that may affect protocol compliance
             or interpretation of outcomes, including active opportunistic infections or advanced
             (severe) infections, or uncontrolled diabetes.
          -  Active autoimmune diseases that require systemic therapy over the past 2 years.
             Replacement therapies (such as thyroxine, insulin, or physiological replacement of
             glucocorticoids due to renal or pituitary deficiency) are allowed.
          -  Assessed by the investigator to be unable or unwilling to comply with the requirements
             of the protocol.