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Neoadjuvant RC48 Plus Gemcitabine in HER2-Expressing MIBC

6 juillet 2026 mis à jour par: 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.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Estimé)

170

Phase

  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

La description

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 d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Seul

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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).
Médicament: 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).
Médicament: 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.
Procédure: 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.
Comparateur actif: 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.
Médicament: 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.
Procédure: 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.
Médicament: 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).

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Pathological Complete Response (pCR)
Délai: 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.

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Incidence of Grade ≥3 Treatment-Related Adverse Events (TRAEs) During Neoadjuvant Therapy
Délai: 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.

Autres mesures de résultats

Mesure des résultats
Description de la mesure
Délai
Clinical Complete Response (cCR)
Délai: 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)
Délai: 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)
Délai: 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.

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Zhiquan Hu

Collaborateurs

Tongji Hospital

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Estimé)

1 juillet 2026

Achèvement primaire (Estimé)

1 juillet 2028

Achèvement de l'étude (Estimé)

1 juillet 2029

Dates d'inscription aux études

Première soumission

28 juin 2026

Première soumission répondant aux critères de contrôle qualité

6 juillet 2026

Première publication (Réel)

9 juillet 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

9 juillet 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

6 juillet 2026

Dernière vérification

1 juin 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • TJ-IRB202605029

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INDÉCIS

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

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