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

Phase Ⅱ Clinical Study on Predicting Perioperative Efficacy of Trastuzumab Rezetecan Combined With Camrelizumab in HER2-Positive Muscle-Invasive Urothelial Carcinoma Based on Multi-Omics

For patients with HER2-expressing muscle-invasive bladder cancer (MIBC), current neoadjuvant therapies dominated by platinum-based chemotherapy remain unsatisfactory with respect to improved clinical efficacy, pathological complete response (pCR) rates, and the achievement rate of tumor downstaging for bladder preservation; in addition, a subset of patients have limited tolerance or eligibility to chemotherapy. Therefore, this study aims to evaluate the neoadjuvant regimen of Ruikang Trastuzumab combined with Camrelizumab, to determine whether this regimen can, with acceptable safety profiles: elevate pCR rate and the proportion of patients downstaged to ≤T1 disease, enable bladder preservation based on TURBT for eligible patients, and explore predictive biomarkers to identify the population most likely to derive clinical benefits.

Study Overview

• Status: Not yet recruiting
• Conditions: Urinary Bladder Cancer; Muscle-Invasive Bladder Cancer (MIBC)
• Intervention / Treatment: Drug: Trastuzumab Rezetecan plus Camrelizumab

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sheng Tai, MD; Phone Number: +86-551-62922234; Email: taisheng@ahmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged ≥18 years old with no restriction on gender.
2. Voluntarily participate in this trial, sign written informed consent form and have good treatment compliance.
3. Histopathologically confirmed bladder urothelial carcinoma (carcinoma with squamous/glandular differentiation is acceptable only when urothelial component dominates the lesion).
4. 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.
5. HER2-positive tumor defined as IHC 1+, 2+ or 3+ tested on archival tumor specimen before enrollment via designated or central laboratory.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
7. Candidates eligible for radical surgery: planned to receive radical cystectomy (RC), and investigators confirm feasibility of subsequent TURBT consistent with study protocol.

8. 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).
9. Fertile subjects agree to use effective contraception throughout study period and for defined duration after last study drug administration.

Exclusion Criteria:

1. Patients with distant metastasis (M1), unresectable disease ineligible for radical surgery, or concomitant active malignancy requiring systematic anti-tumor therapy as assessed by investigator.
2. 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.
3. Previous pelvic radiotherapy, or unrecovered major surgery/severe trauma within predefined time window before enrollment.
4. 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).
5. 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.
6. 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.
7. Known severe hypersensitivity to trastuzumab, camrelizumab or any excipients of investigational drugs; pregnant or breastfeeding females, or those planning pregnancy throughout study period.
8. Severe psychiatric/cognitive disorder or substance abuse preventing regular follow-up and efficacy assessment.
9. Any other conditions inappropriate for trial enrollment such as severe comorbidities or extremely short expected survival, as determined by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Perioperative Therapy with Trastuzumab Rezetecan Combined with Camrelizumab

Drug: Trastuzumab Rezetecan plus Camrelizumab; Eligible screened participants will receive assigned treatment after satisfying all inclusion/exclusion criteria. Neoadjuvant Phase: Patients receive Trastuzumab Rezetecan (4.8 mg/kg, intravenous infusion) plus Camrelizumab (200 mg, intravenous infusion); each treatment cycle lasts 21 days, for a total of 2-3 cycles. Following a 2-4 week rest interval, clinical reassessment is performed prior to radical cystectomy (RC). Postoperative Adjuvant Phase: After surgery, Trastuzumab Rezetecan (4.8 mg/kg, IV infusion, once every 3 weeks for 6 cycles) and Camrelizumab (200 mg, IV infusion once every 3 weeks) are administered, with camrelizumab maintained for up to 1 year.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response Rate (pCR rate)	Proportion of patients achieving pathological complete response (pCR, no residual invasive urothelial carcinoma in bladder and regional lymph nodes) in surgical specimen after perioperative neoadjuvant therapy.	Up to approximately 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-Free Survival (EFS)	Time from study treatment initiation to first occurrence of local recurrence, distant metastasis, disease progression or all-cause death.	From treatment start until disease progression/death, follow-up up to 12 months.
Overall Survival (OS)	Time from study treatment initiation to all-cause death of any reason.	From treatment start until death, follow-up up to 12 months.
Safety and Tolerability	Incidence, severity and causality of adverse events (AEs) graded per CTCAE v6.0 throughout perioperative treatment period.	From first study drug administration to 30 days after last study medication.
Proportion of patients downstaged to T1 stage	Percentage of enrolled patients whose postoperative pathological tumor stage is downstaged to T1 after perioperative therapy.	Up to approximately 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multi-omics spatial biomarkers predicting neoadjuvant treatment response	Correlation between pre-treatment tumor multi-omics profiles (WES whole exome sequencing, 10x Xenium spatial transcriptome, PhenoCycler-Fusion spatial single-cell proteomics) and pathological treatment response; explore predictive factors for perioperative regimen efficacy in HER2-positive MIBC.	Baseline tumor specimen collection before neoadjuvant therapy and matched postoperative pathological outcome.

Collaborators and Investigators

• Sponsor: Sheng Tai
• Investigators: Principal Investigator: Sheng Tai, The First Affiliated Hospital of Anhui Medical University; Principal Investigator: Hanjiang Xu, The First Affiliated Hospital of Anhui Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): June 5, 2026
• Primary Completion (Estimated): June 5, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: June 3, 2026
• First Submitted That Met QC Criteria: June 8, 2026
• First Posted (Actual): June 10, 2026

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urologic Neoplasms; Urinary Bladder Diseases; Urinary Bladder Neoplasms; camrelizumab
• Other Study ID Numbers: KY2026-04-47 (1)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No