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

Official title

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

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.

Detailed description

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.

Interventions

• Drug RC48-ADC
  2.0 mg/kg IV every 2 weeks
• Drug Toripalimab
  3.0 mg/kg IV every 2 weeks
• Drug Gemcitabine
  1000mg/m2 IV infusion on Days 1 and 8 of every 3 week cycle
• Drug Cisplatin
  70mg/m2 IV infusion on Day 1 of every 3 week cycle
• Drug Carboplatin
  AUC=4.5, IV infusion on Day 1 of every 3 week cycle

Primary outcome measures

• Progression-free survival (PFS), evaluated by independent review committee [Time frame: Up to approximately 3 years]
• Overall survival (OS) [Time frame: Up to approximately 3 years]

Secondary outcome measures (4)

• Objective remission rate (ORR) [Time frame: Up to approximately 3 years]
• Progression-free survival (PFS), evaluated by the investigator [Time frame: Up to approximately 3 years]
• Duration of relief (DOR) [Time frame: Up to approximately 3 years]
• Disease control rate (DCR) [Time frame: Up to approximately 3 years]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• Cancer Hospital Chinese Academy of Medical Sciences — Beijing
• Beijing Cancer Hospital — Beijing

Publications

• Sheng X, Zeng G, Zhang C, Zhang Q, Bian J, Niu H, Li J, Shi Y, Yao K, Hu B, Liu Z, Liao H, Yu Z, Jin B, Zhao P, Yang T, Liu X, Qin Y, Xue X, Gou X, Huang J, Gu J, Qi X, Zhang L, Ma G, Liu B, Fang J, Jiang S, He Z, Zhou A, Guo J; RC48-C016 Trial Investigators. Disitamab Vedotin plus Toripalimab in HER2-Expressing Advanced Urothelial Cancer. N Engl J Med. 2025 Dec 11;393(23):2324-2337. doi: 10.1056/ PMID 41124210

Identifiers

NCT: NCT05302284 · RC48-C016

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗