Multi-Omics-Based Phase Ⅱ Trial of Trastuzumab Rezetecan Plus Camrelizumab for Perioperative Therapy in HER2-Positive Muscle-Invasive Urothelial Carcinoma

Inclusion criteria

• Aged ≥18 years old with no restriction on gender.
• Voluntarily participate in this trial, sign written informed consent form and have good treatment compliance.
• Histopathologically confirmed bladder urothelial carcinoma (carcinoma with squamous/glandular differentiation is acceptable only when urothelial component dominates the lesion).
• Clinically or radiologically diagnosed muscle-invasive bladder cancer (MIBC): cT2-T4a, N0-1, M0 per AJCC/UICC staging system; all imaging assessments shall be completed within 28 days prior to enrollment.
• HER2-positive tumor defined as IHC 1+, 2+ or 3+ tested on archival tumor specimen before enrollment via designated or central laboratory.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Candidates eligible for radical surgery: planned to receive radical cystectomy (RC), and investigators confirm feasibility of subsequent TURBT consistent with study protocol.
• Satisfactory major organ function to tolerate perioperative treatment:

• Hematology: ANC ≥1.5×10⁹/L, PLT ≥100×10⁹/L, Hb ≥90 g/L;
• Liver function: ALT/AST ≤2.5×ULN, total bilirubin ≤1.5×ULN;
• Renal function: creatinine clearance ≥50 mL/min calculated by Cockcroft-Gault or MDRD formula;
• Cardiac function: LVEF ≥50% detected by echocardiography without symptomatic heart failure (due to trastuzumab-related cardiac risk).
• Fertile subjects agree to use effective contraception throughout study period and for defined duration after last study drug administration.

Exclusion criteria

• Patients with distant metastasis (M1), unresectable disease ineligible for radical surgery, or concomitant active malignancy requiring systematic anti-tumor therapy as assessed by investigator.
• Prior systemic anti-tumor therapy for current bladder cancer, including neoadjuvant/adjuvant/metastatic chemotherapy, immunotherapy or anti-HER2 agents; previous exposure to PD-1/PD-L1 inhibitors, anti-HER2 monoclonal antibodies or ADCs that may interfere with efficacy or safety evaluation per investigator's judgment.
• Previous pelvic radiotherapy, or unrecovered major surgery/severe trauma within predefined time window before enrollment.
• Active autoimmune disease or patients requiring long-term systemic immunosuppressive therapy (daily prednisone>10 mg or equivalent dose; topical/inhaled/short-course steroid use is permitted).
• Uncontrolled active or severe bacterial infection, active tuberculosis; viral infection: HBsAg positive with elevated HBV DNA without standardized antiviral treatment, positive HCV RNA without disease control, or confirmed HIV infection per local institutional standard; clinically significant cardiovascular disorders including congestive heart failure, recent myocardial infarction, unstable angina, uncontrolled arrhythmia, baseline LVEF<50%, or subjects inappropriate for trastuzumab administration judged by investigator.
• Previous or ongoing interstitial lung disease/non-infectious pneumonitis, or obvious interstitial pulmonary changes on imaging with high risk of immune-related pneumonitis assessed by investigator.
• Known severe hypersensitivity to trastuzumab, camrelizumab or any excipients of investigational drugs; pregnant or breastfeeding females, or those planning pregnancy throughout study period.
• Severe psychiatric/cognitive disorder or substance abuse preventing regular follow-up and efficacy assessment.
• Any other conditions inappropriate for trial enrollment such as severe comorbidities or extremely short expected survival, as determined by the investigator.