A Study of RC48-ADC Combined With Toripalimab For First-line Treatment of Urothelial Carcinoma

A Open-Label, Multicenter, Randomised, Controlled Phase 3 Study of RC48-ADC Plus Toripalimab Versus Chemotherapy Alone in Previously Untreated Unresectable Locally Advanced or Metastatic Urothelial Carcinoma With HER2-Expressing

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.

This is a Phase 3, Open-Label, Multicenter, Randomised, Controlled Study to evaluate the efficacy and safety of RC48-ADC,a recombinant humanized anti-HER2 monoclonal antibody-Monomethyl auristatin E (MMAE) conjugate, in Combination With JS001,a PD-1 monoclonal antibody, for the treatment of Previously Untreated HER2-Expressing Unresectable Locally Advanced or Metastatic Urothelial Carcinoma.

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.