Trastuzumab Rezetecan and Adebrelimab as Neoadjuvant Therapy for HER2-Positive Muscle-Invasive Bladder Cancer

NCT07624201 | Not Yet Recruiting Phase 2

• 1 other identifier: SHR-A1811-1316-BC
• Study Type: interventional
• Target: 58
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to evaluate the efficacy and safety of neoadjuvant trastuzumab rezetecan combined with adebrelimab for the treatment of HER2-positive muscle-invasive bladder cancer.

Conditions

Muscle-Invasive Bladder Cancer (MIBC)

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response

  Assessed by pathological evaluation of resected bladder cancer specimens after neoadjuvant therapy, defined as the proportion of patients with no residual tumor (pT0N0).

  Assessed post-surgery (radical cystectomy or TURBT) on resected tumor specimens after neoadjuvant therapy. Measured postoperatively, up to approximately 4 months after treatment start.

Secondary Outcomes (7)

• Clinical Complete Response Rate

  Assessed by preoperative imaging and surgical evaluation at 3-4 weeks after the last neoadjuvant dose. Up to approximately 4 months after treatment start.

• Pathological Downstaging Rate

  Assessed simultaneously with pCR on postoperative pathological staging. Up to approximately 4 months after treatment start.

• Event-Free Survival

  Time from treatment start to first occurrence of disease progression, recurrence, second primary tumor, or death. Continuously assessed during follow-up, maximum follow-up of 36 months.

• Overall Survival

  Time from treatment start to death from any cause. Continuously assessed, maximum follow-up of 36 months.

• QoL Score

  Assessed by EORTC QLQ-C30 V3.0 at screening, Day 1 of each 21-day cycle (3 cycles), pre-surgery, post-surgery q30d ×3, then q3m (Year 1) and q6m (Years 2-3), up to 36 months.

Study Arms (1)

Experimental Group

EXPERIMENTAL

Trastuzumab Rezetecan Combined with Adebelizumab

Drug: Trastuzumab Rezetecan Combined with Adebelizumab

Interventions

Trastuzumab Rezetecan Combined with Adebelizumab DRUG

Trastuzumab Rezetecan 3.2 mg/kg, Q3W, in combination with Adebrelimab 1200 mg, Q3W, for a total of 3 cycles. Subjects will undergo preoperative imaging and surgical eligibility assessment at 3-4 weeks after the last dose of neoadjuvant therapy. Those who meet the surgical criteria will receive either transurethral resection or radical resection.

Experimental Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years.
• ECOG performance status of 0 or 1.
• Histopathologically diagnosed muscle-invasive bladder cancer (MIBC) (cT2-T4a, N0-1, M0).
• Tumor tissue with HER2 expression (IHC 2+ or 3+) and suitable for radical cystectomy (RC) and transurethral resection of bladder tumor (TURBT).
• No prior systemic chemotherapy.
• At least one measurable lesion per RECIST v1.1 (spiral CT long diameter ≥10 mm or short diameter of enlarged lymph node ≥15 mm) before diagnostic surgery.
• Adequate organ function (no transfusion or hematopoietic growth factor within 2 weeks before blood count screening):
• ANC ≥1.5×10⁹/L
• PLT ≥100×10⁹/L
• Hb ≥90 g/L
• TBIL ≤1.5×ULN (except subjects with Gilbert's syndrome)
• ALT and AST ≤2.5×ULN
• Cr ≤1.5×ULN
• LVEF ≥50%
• QTcF ≤450 ms

You may not qualify if:

• Patients with any active autoimmune disease or history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, etc.); patients with vitiligo; patients with childhood asthma that has completely resolved and requires no intervention in adulthood may be included; patients with asthma requiring bronchodilators for medical intervention are excluded.
• Patients currently using immunosuppressants or systemic corticosteroids for immunosuppressive purposes (dose \>10 mg/day prednisone or equivalent) and continuing use within 2 weeks before the first dose.
• History of severe allergic reactions to other monoclonal antibodies.
• Subjects with untreated central nervous system (CNS) metastases; subjects who have received prior systemic, radical treatment for brain or leptomeningeal metastases (radiotherapy or surgery) may be included if imaging confirms stability for at least 1 month, systemic corticosteroid therapy (dose \>10 mg/day prednisone or equivalent) has been discontinued for more than 2 weeks, and they are asymptomatic.
• Hypertension that cannot be well controlled with antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg).
• Abnormal coagulation function (INR \>2.0, PT \>16 s), bleeding tendency, or currently receiving thrombolytic or anticoagulant therapy; prophylactic use of low-dose aspirin or low molecular weight heparin is permitted.
• Bleeding events of grade ≥2 per CTCAE v6.0 within 4 weeks before the first dose.
• Imaging shows tumor invasion into major blood vessels, or the investigator judges that the tumor has a very high possibility of invading major blood vessels during treatment, leading to fatal massive hemorrhage.
• Arterial/venous thrombotic events within 6 months before the first dose, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism.
• Patients who received prior chemotherapy (including platinum-based chemotherapy) or surgery less than 4 weeks before study drug administration; palliative radiotherapy less than 2 weeks before study drug administration; molecular targeted therapy (including other oral targeted drugs in clinical trials) within less than 5 half-lives before the first study drug dose, or prior treatment-related adverse events (excluding alopecia) not recovered to ≤CTCAE grade 1.
• Patients with radiation enteritis caused by pelvic radiotherapy within 12 months before study drug administration.
• Active infection, unexplained fever ≥38.5°C within 7 days before dosing, or baseline white blood cell count \>15×10⁹/L.
• Known history or evidence of interstitial lung disease or non-infectious pneumonitis that has required corticosteroid therapy; or patients who may interfere with the detection or management of suspected drug-related pulmonary toxicity.
• History of immunodeficiency, including positive HIV serology, or other acquired or congenital immunodeficiency diseases, or known active tuberculosis.
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (HBV reference: HBsAg positive and HBV DNA ≥500 IU/ml; HCV reference: HCV antibody positive and HCV viral load \> upper limit of normal).

Sponsors & Collaborators

• Harbin Medical University: lead
• The Fourth Affiliated Hospital of China Medical University: collaborator
• Tianjin Medical University Second Hospital: collaborator
• First Hospital of China Medical University: collaborator
• Jilin Provincial Tumor Hospital: collaborator

Central Study Contacts

Yangyang Xu, M.D.

CONTACT

+8617703600131; 602037@hrbmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: May 21, 2026
• First Posted: June 3, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: June 3, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share