이 페이지는 자동 번역되었으며 번역의 정확성을 보장하지 않습니다. 참조하십시오 영문판 원본 텍스트의 경우.

Neoadjuvant RC48 Plus Gemcitabine in HER2-Expressing MIBC

2026년 7월 6일 업데이트: 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.

연구 개요

상태

모병

정황

개입 / 치료

연구 유형

중재적

등록 (추정된)

170

단계

  • 3단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

연구 장소

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

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

  • 성인
  • 고령자

건강한 자원 봉사자를 받아들입니다

아니

설명

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.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위
  • 중재 모델: 병렬 할당
  • 마스킹: 하나의

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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).
의약품: 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).
의약품: 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.
절차: 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.
활성 비교기: 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.
의약품: 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.
절차: 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.
의약품: 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).

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Pathological Complete Response (pCR)
기간: 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.

2차 결과 측정

결과 측정
측정값 설명
기간
Incidence of Grade ≥3 Treatment-Related Adverse Events (TRAEs) During Neoadjuvant Therapy
기간: 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.

기타 결과 측정

결과 측정
측정값 설명
기간
Clinical Complete Response (cCR)
기간: 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)
기간: 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)
기간: 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.

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Zhiquan Hu

협력자

Tongji Hospital

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

일반 간행물

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (추정된)

2026년 7월 1일

기본 완료 (추정된)

2028년 7월 1일

연구 완료 (추정된)

2029년 7월 1일

연구 등록 날짜

최초 제출

2026년 6월 28일

QC 기준을 충족하는 최초 제출

2026년 7월 6일

처음 게시됨 (실제)

2026년 7월 9일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 7월 9일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 7월 6일

마지막으로 확인됨

2026년 6월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • TJ-IRB202605029

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

미정

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

아니

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

구독하다