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Neoadjuvant RC48 Plus Gemcitabine in HER2-Expressing MIBC

6 luglio 2026 aggiornato da: 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.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Stimato)

170

Fase

  • Fase 3

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Luoghi di studio

  • Cina
    • Anhui
      • Hefei, Anhui, Cina, 230022
        • Reclutamento
        • The First Affiliated Hospital of Anhui Medical University
        • Contatto:
          • Hanjiang Xu, M.D.
          • Numero di telefono: 18326170623
        • Investigatore principale:
          • Hanjiang Xu, M.D.
    • Fujian
      • Fuzhou, Fujian, Cina, 350001
        • Reclutamento
        • Fujian Medical University Union Hospital
        • Contatto:
        • Investigatore principale:
          • Shaoxing Zhu, M.D.
      • Xiamen, Fujian, Cina, 361003
        • Reclutamento
        • The First Affiliated Hospital of Xiamen University
        • Investigatore principale:
          • Wei Li, M.D.
        • Contatto:
          • Wei Li, M.D.
          • Numero di telefono: 13666028912
    • Guangdong
      • Guangzhou, Guangdong, Cina, 510280
        • Reclutamento
        • ZhuJiang Hospital of Southern Medical University
        • Contatto:
        • Investigatore principale:
          • Abai Xu, M.D.
      • Shenzhen, Guangdong, Cina, 518117
        • Reclutamento
        • Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center
        • Contatto:
        • Investigatore principale:
          • Dongwen Wang, M.D.
    • Hubei
      • Enshi, Hubei, Cina, 445000
        • Reclutamento
        • The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture
        • Contatto:
          • Su Chen, M.D.
          • Numero di telefono: 13477894099
        • Investigatore principale:
          • Su Chen, M.D.
      • Huanggang, Hubei, Cina, 438000
        • Reclutamento
        • Huanggang Central Hospital
        • Contatto:
        • Investigatore principale:
          • Jiayi Tao, M.D.
      • Huangshi, Hubei, Cina, 435000
        • Reclutamento
        • Huangshi Central Hospital
        • Contatto:
        • Investigatore principale:
          • Dingwen Gui, M.D.
      • Jingmen, Hubei, Cina, 448000
        • Reclutamento
        • Jingmen Central Hospital
        • Contatto:
        • Investigatore principale:
          • Zeming Liao, M.D.
      • Jingzhou, Hubei, Cina, 434020
        • Reclutamento
        • Jingzhou Central Hospital
        • Contatto:
          • Yixiang Liao, M.D.
          • Numero di telefono: 18107167675
          • Email: 25261193@qq.com
        • Investigatore principale:
          • Yixiang Liao, M.D.
      • Jingzhou, Hubei, Cina, 434000
        • Reclutamento
        • Jingzhou First People's Hospital
        • Contatto:
        • Investigatore principale:
          • Haitao Dai, M.D.
      • Shiyan, Hubei, Cina, 442000
        • Reclutamento
        • Taihe Hospital
        • Contatto:
          • Congbo Chen, M.D.
          • Numero di telefono: 13907204825
        • Investigatore principale:
          • Congbo Chen, M.D.
      • Wuhan, Hubei, Cina, 430071
        • Reclutamento
        • Zhongnan Hospital of Wuhan University
        • Contatto:
        • Investigatore principale:
          • Xingyuan Xiao, M.D.
      • Wuhan, Hubei, Cina, 430060
        • Reclutamento
        • Renmin Hospital of Wuhan University
        • Contatto:
        • Investigatore principale:
          • Zhiyuan Chen, M.D.
      • Wuhan, Hubei, Cina, 430079
        • Reclutamento
        • Hubei Cancer Hospital
        • Contatto:
        • Investigatore principale:
          • Diansheng Cui, M.D.
      • Wuhan, Hubei, Cina, 430022
        • Reclutamento
        • Wuhan No.1 Hospital
        • Contatto:
        • Investigatore principale:
          • Gaofeng Zhou, M.D.
      • Wuhan, Hubei, Cina, 430014
        • Reclutamento
        • The Central Hospital of Wuhan
        • Contatto:
        • Investigatore principale:
          • Yonglian Guo, M.D.
      • Wuhan, Hubei, Cina, 430030
        • Reclutamento
        • Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
        • Contatto:
        • Investigatore principale:
          • Zhiquan Hu, M.D.
        • Sub-investigatore:
          • Chunguang Yang, M.D.
        • Sub-investigatore:
          • Haijun Huang, M.M.
      • Xiangyang, Hubei, Cina, 441021
        • Reclutamento
        • Xiangyang Central Hospital
        • Contatto:
        • Investigatore principale:
          • Bin Chen, M.D.
      • Yichang, Hubei, Cina, 443003
        • Reclutamento
        • Yichang Central People's Hospital
        • Contatto:
        • Investigatore principale:
          • Xiaobo Chen, M.D.
    • Jiangxi
      • Nanchang, Jiangxi, Cina, 330006
        • Reclutamento
        • Jiangxi Provincial People's Hospital
        • Contatto:
          • Kehua Jiang, M.D.
          • Numero di telefono: 18571225053
        • Investigatore principale:
          • Kehua Jiang, M.D.
    • Shandong
      • Jinan, Shandong, Cina, 250117
        • Reclutamento
        • Shandong Cancer Hospital And Institute
        • Investigatore principale:
          • Jiasheng Bian, M.D.
        • Contatto:

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Separare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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.
Procedura: 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.
Comparatore attivo: 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.
Procedura: 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).

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Pathological Complete Response (pCR)
Lasso di tempo: 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.

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Incidence of Grade ≥3 Treatment-Related Adverse Events (TRAEs) During Neoadjuvant Therapy
Lasso di tempo: 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.

Altre misure di risultato

Misura del risultato
Misura Descrizione
Lasso di tempo
Clinical Complete Response (cCR)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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.

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Zhiquan Hu

Collaboratori

Tongji Hospital

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

1 luglio 2026

Completamento primario (Stimato)

1 luglio 2028

Completamento dello studio (Stimato)

1 luglio 2029

Date di iscrizione allo studio

Primo inviato

28 giugno 2026

Primo inviato che soddisfa i criteri di controllo qualità

6 luglio 2026

Primo Inserito (Effettivo)

9 luglio 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

9 luglio 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

6 luglio 2026

Ultimo verificato

1 giugno 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • TJ-IRB202605029

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

INDECISO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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