Phase II Study of Trastuzumab Rezetecan or in Combination With Adebrelimab in HER2-Expressing Locally Advanced or Metastatic Urothelial Carcinoma (la/mUC)

NCT07241793 | Recruiting Phase 2 DMC

• 1 other identifier: 2025-FXY-281
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 6

Brief Summary

This is a multicenter, open-label, Phase II clinical trial to evaluate the efficacy and safety of Trastuzumab Rezetecan (SHR-A1811) or in combination with Adebrelimab (SHR-1316) for HER2-expressing locally advanced or metastatic urothelial carcinoma (la/mUC).

Conditions

Urothelial Carcinoma; Advanced Urothelial Carcinoma; Urothelial Carcinoma Recurrent

Keywords

Urothelial carcinoma; Antibody-Drug Conjugate; immune checkpoint inhibitor

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Objective Response Rate (ORR) is defined as the proportion of participants achieving a complete response (CR) or partial response (PR) as determined by RECIST v1.1 criteria, based on radiologic assessment. Responses will be confirmed by at least one subsequent imaging assessment.

  Within approximately 36 months

Secondary Outcomes (8)

• Progression-free Survival (PFS)

  Within approximately 36 months

• Overall Survival (OS)

  Within approximately 36 months

• Disease Control Rate (DCR)

  Within approximately 36 months

• Time to Response (TTR)

  Within approximately 36 months

• Duration of Response (DOR)

  Within approximately 36 months

Study Arms (3)

Cohort 1:Adebrelimab and Trastuzumab Rezetecan in Patients with Prior Systemic Therapy

EXPERIMENTAL

Patients with locally advanced or metastatic UC (la/mUC) who have previously received at least one systemic treatment or experienced relapse/progression within 12 months following the last treatment, or those unable to tolerate treatment due to adverse events.

Drug: Adebrelimab; Drug: Trastuzumab Rezetecan

Cohort 2: Adebrelimab and Trastuzumab Rezetecan in Treatment-Naive or Relapsed Patients

EXPERIMENTAL

Patients locally advanced or metastatic UC (la/mUC) who have not received prior systemic therapy or who have relapsed/progressed more than 12 months after receiving neoadjuvant/adjuvant therapy, or those who cannot tolerate treatment due to adverse events.

Drug: Adebrelimab; Drug: Trastuzumab Rezetecan

Cohort 3: Trastuzumab Rezetecan in Patients with Prior Platinum and Immune Therapy

EXPERIMENTAL

Patients locally advanced or metastatic UC (la/mUC) who have previously been treated with platinum-based chemotherapy (including cisplatin, carboplatin), immune checkpoint inhibitors (such as PD-1, PD-L1 inhibitors), and Disitamab Vedotin .

Drug: Trastuzumab Rezetecan

Interventions

Adebrelimab DRUG

Adebrelimab (1200 mg) every 3 weeks (Q3W).

Cohort 1:Adebrelimab and Trastuzumab Rezetecan in Patients with Prior Systemic Therapy; Cohort 2: Adebrelimab and Trastuzumab Rezetecan in Treatment-Naive or Relapsed Patients

Trastuzumab Rezetecan DRUG

Trastuzumab Rezetecan (4.8 mg/kg) every 3 weeks (Q3W).

Cohort 1:Adebrelimab and Trastuzumab Rezetecan in Patients with Prior Systemic Therapy; Cohort 2: Adebrelimab and Trastuzumab Rezetecan in Treatment-Naive or Relapsed Patients; Cohort 3: Trastuzumab Rezetecan in Patients with Prior Platinum and Immune Therapy

Eligibility Criteria

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

You may qualify if:

• Patients included in this study must meet all of the following criteria:
• Age ≥ 18 years;
• Histologically or cytologically confirmed HER2-expressing locally advanced unresectable (e.g., T4b, or N2-3) or metastatic urothelial carcinoma (la/mUC), including bladder, ureter, renal pelvis, and urethra. HER2 expression is defined as immunohistochemical (IHC) staining results of 1+ to 3+, and must be confirmed by the pathology department of Sun Yat-sen University Cancer Center according to ASCO/CAP guidelines.
• Cohort 1: Patients who have received at least one prior systemic therapy, or relapsed/progressed within 12 months after the last treatment, or who could not tolerate treatment due to adverse events (AEs). Cohort 2: Patients who have not received prior systemic therapy or relapsed/progressed more than 12 months after neoadjuvant/adjuvant therapy, or those who could not tolerate treatment due to AEs. Cohort 3: Patients who have previously received platinum-based chemotherapy (including cisplatin, carboplatin, etc.), immunotherapy (including PD-1, PD-L1 inhibitors), and Disitamab Vedotin ;
• At least one measurable target lesion according to RECIST 1.1 criteria;
• ECOG performance status ≤ 2;
• Adequate bone marrow, renal (calculated creatinine clearance \> 30 mL/min using the CG formula), hepatic, and coagulation function;
• Expected survival ≥ 3 months;
• The patient understands the study procedures and has provided written informed consent to participate in the study;
• Female participants of childbearing potential must have a negative urine or serum pregnancy test within 7 days before the first administration of the study drug (Cycle 1, Day 1). If the urine pregnancy test is inconclusive, a blood pregnancy test is required.
• Both male and female participants must agree to use highly effective contraception (i.e., methods with a failure rate of less than 1% per year) and continue contraception until at least 180 days after the end of study treatment.

You may not qualify if:

• Locally advanced patients who are candidates for curative local treatment;
• Clinical history of cardiovascular, liver, respiratory, renal, hematological, endocrine, or neurological/psychiatric diseases;
• Known or untreated spinal cord compression or active central nervous system metastases, except for those who have been treated and stable for at least 1 month and have discontinued corticosteroids for \> 2 weeks;
• Known severe allergic reactions to the study drug's active ingredients and/or excipients, or allergy to humanized monoclonal antibody products (e.g., trastuzumab, pertuzumab);
• Received antitumor monoclonal antibody treatment within 4 weeks before the study start, or received other antitumor therapy without recovery from adverse events;
• Participated in any investigational drug treatment within 4 weeks before the study started;
• Known or suspected interstitial lung disease, or moderate to severe pulmonary diseases that might interfere with the evaluation of drug-related pulmonary toxicity, including but not limited to idiopathic pulmonary fibrosis, organizing pneumonia, bronchitis obliterans, pulmonary embolism, severe asthma, COPD, restrictive pulmonary diseases, or any autoimmune, connective tissue or inflammatory lung diseases, such as rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc., or a history of total lung resection;
• Known hereditary or acquired bleeding disorders (e.g., hemophilia, coagulopathy);
• Received spinal cord radiation or has not recovered from radiation-related adverse events within 4 weeks before study start;
• Diagnosed with immunodeficiency or received systemic corticosteroid treatment or any other immunosuppressive therapy within 7 days before the first study drug administration. Physiological doses of corticosteroids (≤10 mg/day of prednisone or equivalent) are allowed;
• Active autoimmune diseases requiring systemic treatment within the past 2 years (e.g., requiring disease-modifying drugs, corticosteroids, or immunosuppressants). Replacement therapies (e.g., thyroid hormones, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic treatments. A history of non-infectious pneumonia requiring corticosteroid treatment or current interstitial lung disease within 1 year before the first dose is excluded;
• History of organ or hematopoietic stem cell transplantation;
• Known HIV infection (HIV 1/2 positive);
• Untreated active hepatitis B (HBV). Note: Hepatitis B carriers with an HBV viral load \< 1000 copies/mL (200 IU/mL) before the first dose are eligible, but should receive antiviral therapy during chemotherapy to prevent reactivation.
• For anti-HBc (+), HBsAg (-), anti-HBs (-), and undetectable HBV viral load subjects, preventive antiviral therapy is not required, but close monitoring is necessary.

Sponsors & Collaborators

• Tongji Hospital: collaborator
• Sun Yat-sen University: lead
• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: collaborator
• The fifth Affiliated Hospital of Guangzhou Medcial University: collaborator
• The Second Affiliated Hospital of Kunming Medical University: collaborator

Study Sites (6)

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Guangzhou, Guangdong, 510000, China

NOT YET RECRUITING

Sun yat-sen university cancer center

Guangzhou, Guangdong, 510000, China

RECRUITING

The fifth Affiliated Hospital of Guangzhou Medcial University

Guangzhou, Guangdong, 510000, China

RECRUITING

Tongji Hospital, Affiliated to Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, 430030, China

NOT YET RECRUITING

Jiangxi Cancer Center

Nanchang, Jiangxi, 330000, China

RECRUITING

The Second Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, 650033, China

NOT YET RECRUITING

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Yanxia Shi, Doctor

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yanxia Shi, Doctor

CONTACT

86-020-87343486; shiyx@sysucc.org.cn

Haifeng Li, Doctor

CONTACT

86-020-87343486; lihf@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Study Design: Cohort 1: Patients with locally advanced or metastatic UC (la/mUC) who have previously received at least one systemic treatment or experienced relapse/progression within 12 months following the last treatment, or those who are unable to tolerate treatment due to adverse events. Cohort 2: Patients with locally advanced or metastatic UC (la/mUC) who have not received prior systemic therapy or who have relapsed/progressed more than 12 months after receiving neoadjuvant/adjuvant therapy, or those who cannot tolerate treatment due to adverse events. Cohort 3: Patients with locally advanced or metastatic UC (la/mUC) who have previously been treated with platinum-based chemotherapy (including cisplatin, carboplatin), immune checkpoint inhibitors (such as PD-1, PD-L1 inhibitors), and Disitamab Vedotin .

Study Record Dates

• First Submitted: September 24, 2025
• First Posted: November 21, 2025
• Study Start: November 20, 2025
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2031
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)