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

NCT ID: NCT07241793

Last Updated: 2025-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

96 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-11-20

Study Completion Date

2031-07-01

Brief Summary

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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).

Detailed Description

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This multicenter Phase II study aims to investigate the clinical 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). The study includes three cohorts based on their prior treatment history and relapse/progression status: Cohort 1 includes patients who have received at least one prior systemic therapy and relapsed/progressed within 12 months; Cohort 2 includes patients who have not received prior systemic therapy or relapsed/progressed more than 12 months after neo-adjuvant/adjuvant treatment; Cohort 3 includes patients who have previously received platinum-based chemotherapy, immunotherapy, or Disitamab Vedotin. The study will provide important data on the combination therapy of Trastuzumab Rezetecan and Adebrelimab, potentially offering a new treatment option for patients with HER2-expressing advanced UC .

Conditions

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Urothelial Carcinoma Advanced Urothelial Carcinoma Urothelial Carcinoma Recurrent

Keywords

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Urothelial carcinoma Antibody-Drug Conjugate immune checkpoint inhibitor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

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 .
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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

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.

Group Type EXPERIMENTAL

Adebrelimab

Intervention Type DRUG

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

Trastuzumab Rezetecan

Intervention Type DRUG

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

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

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.

Group Type EXPERIMENTAL

Adebrelimab

Intervention Type DRUG

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

Trastuzumab Rezetecan

Intervention Type DRUG

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

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

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 .

Group Type EXPERIMENTAL

Trastuzumab Rezetecan

Intervention Type DRUG

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

Interventions

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Adebrelimab

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

Intervention Type DRUG

Trastuzumab Rezetecan

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patients included in this study must meet all of the following criteria:

1. Age ≥ 18 years;
2. 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.
3. 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 ;
4. At least one measurable target lesion according to RECIST 1.1 criteria;
5. ECOG performance status ≤ 2;
6. Adequate bone marrow, renal (calculated creatinine clearance \> 30 mL/min using the CG formula), hepatic, and coagulation function;
7. Expected survival ≥ 3 months;
8. The patient understands the study procedures and has provided written informed consent to participate in the study;
9. 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.
10. 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.

Exclusion Criteria

1. Locally advanced patients who are candidates for curative local treatment;
2. Clinical history of cardiovascular, liver, respiratory, renal, hematological, endocrine, or neurological/psychiatric diseases;
3. 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;
4. 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);
5. Received antitumor monoclonal antibody treatment within 4 weeks before the study start, or received other antitumor therapy without recovery from adverse events;
6. Participated in any investigational drug treatment within 4 weeks before the study started;
7. 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;
8. Known hereditary or acquired bleeding disorders (e.g., hemophilia, coagulopathy);
9. Received spinal cord radiation or has not recovered from radiation-related adverse events within 4 weeks before study start;
10. 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;
11. 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;
12. History of organ or hematopoietic stem cell transplantation;
13. Known HIV infection (HIV 1/2 positive);
14. 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.
15. Active hepatitis C (HCV) infection (HCV antibody positive and HCV RNA level above detection threshold;
16. Received live vaccines within 30 days before the first dose of the study drug. Note: Inactivated flu vaccines are allowed within 30 days before the first dose, but live attenuated flu vaccines are not permitted.
17. History of other malignancies within the past 3 years, except for cured non-melanoma skin cancer, cervical carcinoma in situ, or low-risk prostate cancer (T2N0M0, Gleason score \<7, or undetectable PSA);
18. Any condition or disease history that may interfere with the study results or hinder the participant's full participation, including abnormal laboratory values, or situations deemed inappropriate by the investigator;
19. Breastfeeding women.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The fifth Affiliated Hospital of Guangzhou Medcial University

OTHER_GOV

Sponsor Role collaborator

The Second Affiliated Hospital of Kunming Medical University

OTHER

Sponsor Role collaborator

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

OTHER

Sponsor Role collaborator

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

UNKNOWN

Sponsor Role collaborator

Sun Yat-sen University

OTHER

Sponsor Role lead

Responsible Party

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Shi Yanxia

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Yanxia Shi, Doctor

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

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

Guangzhou, Guangdong, China

Site Status RECRUITING

Sun yat-sen university cancer center

Guangzhou, Guangdong, China

Site Status RECRUITING

The fifth Affiliated Hospital of Guangzhou Medcial University

Guangzhou, Guangdong, China

Site Status RECRUITING

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

Wuhan, Hubei, China

Site Status RECRUITING

The Second Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Yanxia Shi, Doctor

Role: CONTACT

Phone: 86-020-87343486

Email: [email protected]

Haifeng Li, Doctor

Role: CONTACT

Phone: 86-020-87343486

Email: [email protected]

Facility Contacts

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Tao Qin, Doctor

Role: primary

Yanxia Shi, Doctor

Role: primary

Haifeng Li, Doctor

Role: backup

Guifang Yu, Doctor

Role: primary

Bo Liu, Doctor

Role: primary

Xuefen Lei, Doctor

Role: primary

Other Identifiers

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2025-FXY-281

Identifier Type: -

Identifier Source: org_study_id