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Neoadjuvant RC48 Plus Gemcitabine in HER2-Expressing MIBC

6. Juli 2026 aktualisiert von: 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.

Studienübersicht

Status

Rekrutierung

Bedingungen

Intervention / Behandlung

Studientyp

Interventionell

Einschreibung (Geschätzt)

170

Phase

  • Phase 3

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienkontakt

Studienorte

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

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

  • Erwachsene
  • Älterer Erwachsener

Akzeptiert gesunde Freiwillige

Nein

Beschreibung

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.

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Single

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
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).
Arzneimittel: 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).
Arzneimittel: 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.
Verfahren: 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.
Aktiver Komparator: 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.
Arzneimittel: 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.
Verfahren: 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.
Arzneimittel: 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).

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Pathological Complete Response (pCR)
Zeitfenster: 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.

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Incidence of Grade ≥3 Treatment-Related Adverse Events (TRAEs) During Neoadjuvant Therapy
Zeitfenster: 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.

Andere Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Clinical Complete Response (cCR)
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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.

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Zhiquan Hu

Mitarbeiter

Tongji Hospital

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Geschätzt)

1. Juli 2026

Primärer Abschluss (Geschätzt)

1. Juli 2028

Studienabschluss (Geschätzt)

1. Juli 2029

Studienanmeldedaten

Zuerst eingereicht

28. Juni 2026

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

6. Juli 2026

Zuerst gepostet (Tatsächlich)

9. Juli 2026

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

9. Juli 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

6. Juli 2026

Zuletzt verifiziert

1. Juni 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • TJ-IRB202605029

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UNENTSCHIEDEN

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Nein

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

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