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).
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;
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);
Parallel
Adebrelimab
DrugAdebrelimab (1200 mg) every 3 weeks (Q3W).
Trastuzumab Rezetecan
DrugTrastuzumab Rezetecan (4.8 mg/kg) every 3 weeks (Q3W).
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.
Progression-free Survival (PFS)
Progression-Free Survival (PFS) is defined as the time from the first dose of study treatment to the first documented disease progression, as determined by RECIST v1.1, or death from any cause, whichever occurs first. Disease progression will be assessed by independent radiologic review. Patients without documented progression or death at the time of analysis will be censored at their last tumor assessment date.
Overall Survival (OS)
Overall Survival (OS) is defined as the time from the first dose of study treatment to death from any cause. Participants still alive at the time of analysis will be censored at the date of their last follow-up.
Disease Control Rate (DCR)
Disease Control Rate (DCR) is defined as the proportion of participants achieving a complete response (CR), partial response (PR), or stable disease (SD) for at least 6 weeks after treatment initiation, based on RECIST v1.1 criteria.
Time to Response (TTR)
Time to Response (TTR) is defined as the time from the first dose of study treatment to the first occurrence of a confirmed objective response (CR or PR) as determined by RECIST v1.1 criteria.
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Sun Yat-sen University
Lead sponsor
The fifth Affiliated Hospital of Guangzhou Medcial University
Collaborator
The Second Affiliated Hospital of Kunming Medical University
Collaborator
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Collaborator
Tongji Hospital
Collaborator
