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Neoadjuvant RC48 Plus Gemcitabine in HER2-Expressing MIBC

6 de julio de 2026 actualizado por: Zhiquan Hu

Neoadjuvant RC48 Plus Gemcitabine for HER2 1~3+ MIBC: A Prospective, Multicenter, Randomized, Controlled, Non-inferiority Study (GUARD-02)

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.

Descripción general del estudio

Estado

Reclutamiento

Condiciones

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Estimado)

170

Fase

  • Fase 3

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

Ubicaciones de estudio

  • Porcelana
    • Anhui
      • Hefei, Anhui, Porcelana, 230022
        • Reclutamiento
        • The First Affiliated Hospital of Anhui Medical University
        • Contacto:
          • Hanjiang Xu, M.D.
          • Número de teléfono: 18326170623
        • Investigador principal:
          • Hanjiang Xu, M.D.
    • Fujian
      • Fuzhou, Fujian, Porcelana, 350001
        • Reclutamiento
        • Fujian Medical University Union Hospital
        • Contacto:
          • Shaoxing Zhu, M.D.
          • Número de teléfono: 18758872716
          • Correo electrónico: zsxing2005@126.com
        • Investigador principal:
          • Shaoxing Zhu, M.D.
      • Xiamen, Fujian, Porcelana, 361003
        • Reclutamiento
        • The First Affiliated Hospital of Xiamen University
        • Investigador principal:
          • Wei Li, M.D.
        • Contacto:
          • Wei Li, M.D.
          • Número de teléfono: 13666028912
    • Guangdong
      • Guangzhou, Guangdong, Porcelana, 510280
        • Reclutamiento
        • ZhuJiang Hospital of Southern Medical University
        • Contacto:
          • Abai Xu, M.D.
          • Número de teléfono: 18665626790
          • Correo electrónico: lc96xab@163.com
        • Investigador principal:
          • Abai Xu, M.D.
      • Shenzhen, Guangdong, Porcelana, 518117
        • Reclutamiento
        • Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center
        • Contacto:
          • Dongwen Wang, M.D.
          • Número de teléfono: 13530336918
          • Correo electrónico: urology2007@126.com
        • Investigador principal:
          • Dongwen Wang, M.D.
    • Hubei
      • Enshi, Hubei, Porcelana, 445000
        • Reclutamiento
        • The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture
        • Contacto:
          • Su Chen, M.D.
          • Número de teléfono: 13477894099
        • Investigador principal:
          • Su Chen, M.D.
      • Huanggang, Hubei, Porcelana, 438000
        • Reclutamiento
        • Huanggang Central Hospital
        • Contacto:
          • Jiayi Tao, M.D.
          • Número de teléfono: 13409868766
          • Correo electrónico: 35149051@qq.com
        • Investigador principal:
          • Jiayi Tao, M.D.
      • Huangshi, Hubei, Porcelana, 435000
        • Reclutamiento
        • Huangshi Central Hospital
        • Contacto:
          • Dingwen Gui, M.D.
          • Número de teléfono: 13971778131
          • Correo electrónico: 68661272@qq.com
        • Investigador principal:
          • Dingwen Gui, M.D.
      • Jingmen, Hubei, Porcelana, 448000
        • Reclutamiento
        • Jingmen Central Hospital
        • Contacto:
          • Zeming Liao, M.D.
          • Número de teléfono: 13886919765
          • Correo electrónico: lzm19731217@qq.com
        • Investigador principal:
          • Zeming Liao, M.D.
      • Jingzhou, Hubei, Porcelana, 434020
        • Reclutamiento
        • Jingzhou Central Hospital
        • Contacto:
          • Yixiang Liao, M.D.
          • Número de teléfono: 18107167675
          • Correo electrónico: 25261193@qq.com
        • Investigador principal:
          • Yixiang Liao, M.D.
      • Jingzhou, Hubei, Porcelana, 434000
        • Reclutamiento
        • Jingzhou First People's Hospital
        • Contacto:
          • Haitao Dai, M.D.
          • Número de teléfono: 18163138773
          • Correo electrónico: 124316578@qq.com
        • Investigador principal:
          • Haitao Dai, M.D.
      • Shiyan, Hubei, Porcelana, 442000
        • Reclutamiento
        • Taihe Hospital
        • Contacto:
          • Congbo Chen, M.D.
          • Número de teléfono: 13907204825
        • Investigador principal:
          • Congbo Chen, M.D.
      • Wuhan, Hubei, Porcelana, 430071
        • Reclutamiento
        • Zhongnan Hospital of Wuhan University
        • Contacto:
        • Investigador principal:
          • Xingyuan Xiao, M.D.
      • Wuhan, Hubei, Porcelana, 430060
        • Reclutamiento
        • Renmin Hospital of Wuhan University
        • Contacto:
        • Investigador principal:
          • Zhiyuan Chen, M.D.
      • Wuhan, Hubei, Porcelana, 430079
        • Reclutamiento
        • Hubei Cancer Hospital
        • Contacto:
          • Diansheng Cui, M.D.
          • Número de teléfono: 13871549210
          • Correo electrónico: 787434798@qq.com
        • Investigador principal:
          • Diansheng Cui, M.D.
      • Wuhan, Hubei, Porcelana, 430022
        • Reclutamiento
        • Wuhan No.1 Hospital
        • Contacto:
          • Gaofeng Zhou, M.D.
          • Número de teléfono: 18507134410
          • Correo electrónico: 910790776@qq.com
        • Investigador principal:
          • Gaofeng Zhou, M.D.
      • Wuhan, Hubei, Porcelana, 430014
        • Reclutamiento
        • The Central Hospital of Wuhan
        • Contacto:
          • Yonglian Guo, M.D.
          • Número de teléfono: 15972152299
          • Correo electrónico: 15972152299@139.com
        • Investigador principal:
          • Yonglian Guo, M.D.
      • Wuhan, Hubei, Porcelana, 430030
        • Reclutamiento
        • Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
        • Contacto:
        • Investigador principal:
          • Zhiquan Hu, M.D.
        • Sub-Investigador:
          • Chunguang Yang, M.D.
        • Sub-Investigador:
          • Haijun Huang, M.M.
      • Xiangyang, Hubei, Porcelana, 441021
        • Reclutamiento
        • Xiangyang Central Hospital
        • Contacto:
          • Bin chen, M.D.
          • Número de teléfono: 19908671399
          • Correo electrónico: 625848080@qq.com
        • Investigador principal:
          • Bin Chen, M.D.
      • Yichang, Hubei, Porcelana, 443003
        • Reclutamiento
        • Yichang Central People's Hospital
        • Contacto:
          • Xiaobo Chen, M.D.
          • Número de teléfono: 13972587419
          • Correo electrónico: 272899447@qq.com
        • Investigador principal:
          • Xiaobo Chen, M.D.
    • Jiangxi
      • Nanchang, Jiangxi, Porcelana, 330006
        • Reclutamiento
        • Jiangxi Provincial People's Hospital
        • Contacto:
          • Kehua Jiang, M.D.
          • Número de teléfono: 18571225053
        • Investigador principal:
          • Kehua Jiang, M.D.
    • Shandong
      • Jinan, Shandong, Porcelana, 250117
        • Reclutamiento
        • Shandong Cancer Hospital And Institute
        • Investigador principal:
          • Jiasheng Bian, M.D.
        • Contacto:

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

  • Adulto
  • Adulto Mayor

Acepta Voluntarios Saludables

No

Descripción

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.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Único

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Experimental Arm (RC48 + Gemcitabine)
Patients in this arm receive neoadjuvant Disitamab Vedotin (RC48) at a dose of 2.0 mg/kg via intravenous (IV) infusion (60-90 minutes) on Day 1, followed by Gemcitabine 1000 mg/m² IV on Day 2. The regimen is administered every 2 weeks (Q2W). Tumor response is evaluated via imaging after 3 cycles. Patients who do not achieve a clinical complete response (cCR) will continue the treatment for an additional 3 cycles (totaling 3 to 6 cycles).
Droga: Gemcitabine
On Day 2 of each neoadjuvant therapy cycle, a dose of 1000 mg/m² is administered via intravenous infusion. The regimen is administered every 2 weeks (Q2W).
Droga: Disitamab Vedotin (RC48)
On Day 1 of each neoadjuvant therapy cycle, a dose of 2 mg/kg is administered via intravenous infusion over 30-60 minutes.
Procedimiento: Radical Cystectomy
Patients are scheduled to undergo radical cystectomy (RC) within 4 weeks after the last dose of neoadjuvant therapy, and the postoperative specimens will be assessed for pathological response.
Comparador activo: Active Comparator Arm (RC48 + Toripalimab)
Patients in this arm receive neoadjuvant Disitamab Vedotin (RC48) at a dose of 2.0 mg/kg via IV infusion (60-90 minutes) on Day 1, followed by Toripalimab 3 mg/kg IV on Day 2. The regimen is administered every 2 weeks (Q2W). Tumor response is evaluated via imaging after 3 cycles, with treatment continuing for a total of 3 to 6 cycles based on the tumor response evaluation.
Droga: Disitamab Vedotin (RC48)
On Day 1 of each neoadjuvant therapy cycle, a dose of 2 mg/kg is administered via intravenous infusion over 30-60 minutes.
Procedimiento: Radical Cystectomy
Patients are scheduled to undergo radical cystectomy (RC) within 4 weeks after the last dose of neoadjuvant therapy, and the postoperative specimens will be assessed for pathological response.
Droga: Toripalimab
On Day 2 of each neoadjuvant therapy cycle, a dose of 3 mg/kg is administered via intravenous infusion. The regimen is administered every 2 weeks (Q2W).

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Pathological Complete Response (pCR)
Periodo de tiempo: Within 1 week after completion of radical cystectomy.
Defined as the absence of residual viable tumor cells (ypT0N0) in RC+PLND specimens. Assessed post-surgery. Method: A central pathology review committee performs centralized, blinded independent review of slides from all eligible patients. Sites ship de-identified slides and clinical forms to a central lab for uniform anonymization, QC, H&E staining, and supplementary IHC if needed. All materials are fully de-identified, presented in random order without clinical data. Two senior uropathologists (associate professor level or above) read independently; consensus is final, otherwise a third senior pathologist adjudicates blindly. ypT and ypN are recorded.
Within 1 week after completion of radical cystectomy.

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Incidence of Grade ≥3 Treatment-Related Adverse Events (TRAEs) During Neoadjuvant Therapy
Periodo de tiempo: The period starting from the first administration of neoadjuvant therapy and extending through 4 weeks following the last dose.
Defined as the proportion of patients in the safety set experiencing at least one Grade ≥3 TRAE (CTCAE v5.0) during neoadjuvant therapy. Assessed from the first cycle to 4 weeks after the last cycle, with comprehensive tests each cycle, a scheduled visit 1 week after the last dose of each cycle, and immediate evaluation upon any alert or complaint. Method: Uniform site training, structured eCRF recording of AE terms, dates, grades, relatedness, actions, outcomes. An independent Clinical Endpoint Committee (CEC) conducts centralized, blinded review of all Grade ≥3 events for final adjudication.
The period starting from the first administration of neoadjuvant therapy and extending through 4 weeks following the last dose.

Otras medidas de resultado

Medida de resultado
Medida Descripción
Periodo de tiempo
Clinical Complete Response (cCR)
Periodo de tiempo: Within 1 week after completion of radical cystectomy.
Defined as no clinical evidence of residual tumor in primary and regional nodes after neoadjuvant therapy, assessed hierarchically: surgical patients based on pathological pCR (ypT0/Tis ypN0); non-surgical patients based on imaging CR per RECIST 1.1 (target lesions disappear, nodes <10 mm, no new lesions). Assessed post-neoadjuvant. Method: Surgical patients use central pathology review (same as pCR); non-surgical patients use independent imaging review committee blinded to RECIST 1.1. A CEC reviews all data in blinded fashion, adjudicates cCR per hierarchy, ensuring uniformity.
Within 1 week after completion of radical cystectomy.
Event-Free Survival (EFS)
Periodo de tiempo: From date of first neoadjuvant dose until the date of first documented events above, whichever came first, assessed up to 36 months.
Defined as time from neoadjuvant start to first occurrence of: ① disease progression (local/regional recurrence, distant metastasis, or definite clinical progression); ② death from any cause; ③ initiation of new anti-cancer therapy due to progression or toxicity. Censored at last known event-free assessment. Assessed at scheduled visits. Method: A central follow-up unit conducts structured symptom queries; any suspected event triggers medical evaluation. All potential event materials (imaging, records, symptom logs, death certificates) are submitted to an independent CEC for blinded adjudication of event and date, final for analysis.
From date of first neoadjuvant dose until the date of first documented events above, whichever came first, assessed up to 36 months.
Overall Survival (OS)
Periodo de tiempo: From date of first neoadjuvant dose until the date of death from any cause, assessed up to 36 months.
Defined as time from neoadjuvant start to death from any cause. Assessed at scheduled visits. Method: Central follow-up unit collects objective death documents from multiple sources. The independent CEC reviews all documents in a fully blinded manner, verifies and adjudicates the exact date of death, which serves as the final basis for OS calculation.
From date of first neoadjuvant dose until the date of death from any cause, assessed up to 36 months.

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Zhiquan Hu

Colaboradores

Tongji Hospital

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Publicaciones Generales

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Estimado)

1 de julio de 2026

Finalización primaria (Estimado)

1 de julio de 2028

Finalización del estudio (Estimado)

1 de julio de 2029

Fechas de registro del estudio

Enviado por primera vez

28 de junio de 2026

Primero enviado que cumplió con los criterios de control de calidad

6 de julio de 2026

Publicado por primera vez (Actual)

9 de julio de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

9 de julio de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

6 de julio de 2026

Última verificación

1 de junio de 2026

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • TJ-IRB202605029

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

INDECISO

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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