Denne siden ble automatisk oversatt og nøyaktigheten av oversettelsen er ikke garantert. Vennligst referer til engelsk versjon for en kildetekst.

Neoadjuvant RC48 Plus Gemcitabine in HER2-Expressing MIBC

6. juli 2026 oppdatert av: 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.

Studieoversikt

Status

Rekruttering

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Antatt)

170

Fase

  • Fase 3

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studiesteder

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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

  • Voksen
  • Eldre voksen

Tar imot friske frivillige

Nei

Beskrivelse

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.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Enkelt

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: 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).
Legemiddel: 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).
Legemiddel: 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.
Fremgangsmåte: 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.
Aktiv 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.
Legemiddel: 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.
Fremgangsmåte: 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.
Legemiddel: 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).

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Pathological Complete Response (pCR)
Tidsramme: 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.

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Incidence of Grade ≥3 Treatment-Related Adverse Events (TRAEs) During Neoadjuvant Therapy
Tidsramme: 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.

Andre resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Clinical Complete Response (cCR)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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.

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Zhiquan Hu

Samarbeidspartnere

Tongji Hospital

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Antatt)

1. juli 2026

Primær fullføring (Antatt)

1. juli 2028

Studiet fullført (Antatt)

1. juli 2029

Datoer for studieregistrering

Først innsendt

28. juni 2026

Først innsendt som oppfylte QC-kriteriene

6. juli 2026

Først lagt ut (Faktiske)

9. juli 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

9. juli 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

6. juli 2026

Sist bekreftet

1. juni 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • TJ-IRB202605029

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

UBESLUTTE

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Abonnere