Neoadjuvant RC48 Plus Gemcitabine in HER2-Expressing MIBC | NCT07693959

NCT07693959

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Tongji Hospital	OTHER

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Experimental Arm (RC48 + Gemcitabine)	Experimental	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).	Drug: Gemcitabine Drug: Disitamab Vedotin (RC48) Procedure: Radical Cystectomy
Active Comparator Arm (RC48 + Toripalimab)	Active Comparator	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.	Drug: Toripalimab Drug: Disitamab Vedotin (RC48) Procedure: Radical Cystectomy

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Gemcitabine	Drug	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).	Experimental Arm (RC48 + Gemcitabine)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Pathological Complete Response (pCR)	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.

Secondary Outcomes

Measure	Description	Time Frame
Incidence of Grade ≥3 Treatment-Related Adverse Events (TRAEs) During Neoadjuvant Therapy	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.

Other Outcomes

Measure	Description	Time Frame
Clinical Complete Response (cCR)	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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Informed Consent & Compliance: Provision of signed informed consent and ability to comply with study procedures and follow-up requirements.
Age: Age 18 to 75 years (inclusive).
Planned Surgery: Planned to undergo radical cystectomy (RC) with lymph node dissection (LND).
Clinical Stage: Clinical stage T2-T4aNxM0, as assessed by CT, MRI, or PET-CT.
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).
Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
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
Cardiac Function: New York Heart Association (NYHA) class < 3.
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：

Receipt of live attenuated vaccine within 4 weeks prior to enrollment or planned receipt during the study period.
Receipt of systemic chemotherapy, or anti-PD-1, anti-PD-L1, or HER2-targeted therapy within the past 6 months.
Known hypersensitivity to gemcitabine, disitamab vedotin, toripalimab, or any of their excipients.
Active, known, or suspected autoimmune disease.
Known history of primary immunodeficiency.
History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
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).
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).
History of other malignancies within the past 5 years, excluding clinically cured early-stage tumors.
Active tuberculosis.

PubMed Identifier	Type	Citation	Retractions
41193372	Result	Huang H, Ma W, Zeng X, Liu B, Dai H, Zhou G, Wan J, Zhang Y, Hu Z, Yang C. Efficacy and Safety of Disitamab Vedotin Combined with Gemcitabine as Neoadjuvant Therapy in Muscle-invasive Bladder Cancer: An Open-label, Multicenter, Single-arm, Phase 2 Trial. Eur Urol. 2025 Nov 4:S0302-2838(25)04768-2. doi: 10.1016/j.eururo.2025.10.009. Online ahead of print.
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