Neoadjuvant RC48 plus gemcitabine vs RC48 plus toripalimab for muscle-invasive bladder cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

In this phase 3 study, patients with muscle-invasive bladder cancer who are planned for radical cystectomy are randomized to receive either disitamab vedotin (RC48) plus gemcitabine or RC48 plus toripalimab before surgery. Treatments are given every two weeks for 3 to 6 cycles based on imaging response, followed by radical cystectomy with pelvic lymph node dissection and a trimodality bladder-sparing plan as appropriate. The primary goal is to determine if the RC48–gemcitabine combination is not worse than the RC48–toripalimab combination in achieving pathological complete response. Secondary aims include evaluating safety, surgical outcomes, and post-surgical therapies. Eligible participants are adults 18–75 with HER2-expressing, muscle-invasive disease and adequate organ function.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Informed Consent \& Compliance: Provision of signed informed consent and ability to comply with study procedures and follow-up requirements.
2. Age: Age 18 to 75 years (inclusive).
3. Planned Surgery: Planned to undergo radical cystectomy (RC) with lymph node dissection (LND).
4. Clinical Stage: Clinical stage T2-T4aNxM0, as assessed by CT, MRI, or PET-CT.
5. Pathology \& Biomarker: Histologically confirmed predominant urothelial carcinoma by cystoscopic biopsy or transurethral resection of bladder tumor (TURBT), with HER2 expression of 1+ to 3+ determined by immunohistochemistry (IHC).
6. Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
7. Adequate Organ Function: Laboratory values meeting the following criteria: Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L; Platelet count ≥ 100 × 10\^9/L; Hemoglobin ≥ 80 g/L; Total bilirubin ≤ 1.5 × upper limit of normal (ULN); Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 × ULN
8. Cardiac Function: New York Heart Association (NYHA) class \< 3.
9. Reproductive Status \& Contraception: \*Female: Must be surgically sterile, postmenopausal, or agree to use highly effective contraception during the study and for 6 months after the last dose of study treatment. Must not be lactating. \*Male: Must agree to use a medically acceptable method of contraception (e.g., condoms, abstinence) during the study and for 6 months after the last dose of study treatment.

Exclusion Criteria：

1. Receipt of live attenuated vaccine within 4 weeks prior to enrollment or planned receipt during the study period.
2. Receipt of systemic chemotherapy, or anti-PD-1, anti-PD-L1, or HER2-targeted therapy within the past 6 months.
3. Known hypersensitivity to gemcitabine, disitamab vedotin, toripalimab, or any of their excipients.
4. Active, known, or suspected autoimmune disease.
5. Known history of primary immunodeficiency.
6. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
7. Untreated acute or chronic active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. (Patients receiving continuous antiviral therapy with monitored viral loads may be eligible at the investigator's discretion).
8. Uncontrolled concurrent illness including, but not limited to: human immunodeficiency virus (HIV) infection, active or poorly controlled severe infection, or evidence of uncontrolled systemic disease (e.g., severe psychiatric/neurological disorders, decompensated respiratory failure).
9. History of other malignancies within the past 5 years, excluding clinically cured early-stage tumors.
10. Active tuberculosis.

Where it's running

• The First Affiliated Hospital of Anhui Medical University
  Hefei, Anhui, China Recruiting
• Fujian Medical University Union Hospital
  Fuzhou, Fujian, China Recruiting
• The First Affiliated Hospital of Xiamen University
  Xiamen, Fujian, China Recruiting
• Zhujiang Hospital of Southern Medical University
  Guangzhou, Guangdong, China Recruiting
• Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center
  Shenzhen, Guangdong, China Recruiting
• The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture
  Enshi, Hubei, China Recruiting

Study contacts

• Study coordinator: Zhiquan Hu, M.D.
• Email: huzhiquan2000@163.com
• Phone: 13971656164

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.