Neoadjuvant RC48 Plus Gemcitabine in HER2-Expressing MIBC

Recruiting now · Phase 3

Conditions studied: MIBC

In brief

Objectives: To evaluate the non-inferiority of disitamab vedotin plus gemcitabine versus disitamab vedotin plus toripalimab in terms of the pathological complete response (pCR) rate as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC). This study is designed to evaluate two parallel neoadjuvant treatment strategies followed by definitive local therapy and adjuvant treatment. Eligible patients will be assigned to either the Experimental Arm, receiving neoadjuvant Disitamab Vedotin (RC48) combined with Gemcitabine, or the Active Comparator Arm, receiving neoadjuvant RC48 combined with Toripalimab. Both neoadjuvant regimens are administered every two weeks for 3 to 6 cycles, contingent upon imaging-based tumor response. Following the neoadjuvant phase, patients from both arms will proceed to receive standard Radical Cystectomy (RC) combined with Pelvic Lymph Node Dissection (PLND) within four weeks of their final dose, with a trimodality therapy (TMT) bladder-sparing approach strictly restricted to a selected minority of patients. In the postoperative phase, eligible patients will receive adjuvant therapy consisting of RC48 plus Toripalimab for 6 cycles, followed by Toripalimab maintenance monotherapy for a duration of ≤ 1 year (or a maximum of 1 year).Patients post-RC require abdominopelvic/chest imaging q3-6m; non-RC patients need cystoscopy q3m and abdominopelvic/chest CT q3-6m. Follow-up staff should proactively contact patients q3m to record imaging findings and inquire about hematuria, stomal lesions, cough/chest pain, CNS symptoms, and accurately document recurrence/progression, metastasis, death with dates.

Key facts

Study ID

NCT07693959

Run by

Zhiquan Hu

People needed

170

Starts

2026-07-01

Expected to finish

2029-07-01

Last updated by the study team

2026-07-09

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Informed Consent \& Compliance: Provision of signed informed consent and ability to comply with study procedures and follow-up requirements.
• Age: Age 18 to 75 years (inclusive).
• Planned Surgery: Planned to undergo radical cystectomy (RC) with lymph node dissection (LND).
• Clinical Stage: Clinical stage T2-T4aNxM0, as assessed by CT, MRI, or PET-CT.
• 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).
• Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• 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
• Cardiac Function: New York Heart Association (NYHA) class < 3.
• 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：
• Receipt of live attenuated vaccine within 4 weeks prior to enrollment or planned receipt during the study period.
• Receipt of systemic chemotherapy, or anti-PD-1, anti-PD-L1, or HER2-targeted therapy within the past 6 months.
• Known hypersensitivity to gemcitabine, disitamab vedotin, toripalimab, or any of their excipients.
• Active, known, or suspected autoimmune disease.
• Known history of primary immunodeficiency.
• History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• 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).
• 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).
• History of other malignancies within the past 5 years, excluding clinically cured early-stage tumors.
• Active tuberculosis.

Where it is running

• The First Affiliated Hospital of Anhui Medical University — Hefei, Anhui, China (enrolling)
• Fujian Medical University Union Hospital — Fuzhou, Fujian, China (enrolling)
• The First Affiliated Hospital of Xiamen University — Xiamen, Fujian, China (enrolling)
• Zhujiang Hospital of Southern Medical University — Guangzhou, Guangdong, China (enrolling)
• Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center — Shenzhen, Guangdong, China (enrolling)
• The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture — Enshi, Hubei, China (enrolling)
• Huanggang Central Hospital — Huanggang, Hubei, China (enrolling)
• Huangshi Central Hospital — Huangshi, Hubei, China (enrolling)
• Jingmen Central Hospital — Jingmen, Hubei, China (enrolling)
• Jingzhou First People's Hospital — Jingzhou, Hubei, China (enrolling)
• Jingzhou Central Hospital — Jingzhou, Hubei, China (enrolling)
• Taihe Hospital — Shiyan, Hubei, China (enrolling)
• The Central Hospital of Wuhan — Wuhan, Hubei, China (enrolling)
• Wuhan No.1 Hospital — Wuhan, Hubei, China (enrolling)
• Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (enrolling)
• Renmin Hospital of Wuhan University — Wuhan, Hubei, China (enrolling)
• Zhongnan Hospital of Wuhan University — Wuhan, Hubei, China (enrolling)
• Hubei Cancer Hospital — Wuhan, Hubei, China (enrolling)
• Xiangyang Central Hospital — Xiangyang, Hubei, China (enrolling)
• Yichang Central People's Hospital — Yichang, Hubei, China (enrolling)
• Jiangxi Provincial People's Hospital — Nanchang, Jiangxi, China (enrolling)
• Shandong Cancer Hospital and Institute — Jinan, Shandong, China (enrolling)

Full record on ClinicalTrials.gov

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