The purpose of this Phase II, open-label, multicenter, randomized controlled study is to evaluate the efficacy and safety of Enfortumab Vedotin in combination with Toripalimab compared to Gemcitabine plus Cisplatin. This regimen is evaluated as a neoadjuvant treatment for patients with locally advanced or high-risk muscle-invasive bladder cancer. Participants will be randomly assigned in a 1:1 ratio to one of two cohorts. Cohort A will receive Enfortumab Vedotin and Toripalimab for 3 treatment cycles. Cohort B will receive Gemcitabine and Cisplatin for 3 treatment cycles. Following the neoadjuvant treatment phase, patients will undergo radical cystectomy and pelvic lymph node dissection. The primary endpoint of the study is the 1-year Event-Free Survival (EFS) rate. Secondary endpoints include pathological downstaging rate (pDR), pathological complete response (pCR), Disease-Free Survival (DFS), Overall Survival (OS), and the assessment of adverse events. Additionally, the study will evaluate the relationship between treatment efficacy and the expression of PD-L1 and Nectin-4 in tumor tissues.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
58
Enfortumab Vedotin is administered intravenously at a dose of 1.25 mg/kg on Day 1 and Day 8 of each 21-day cycle for a total of 3 cycles
Toripalimab is administered intravenously at a dose of 240 mg on Day 1 of each 21-day cycle for a total of 3 cycles.
Gemcitabine is administered intravenously at a dose of 1000 mg/m² on Day 1 and Day 8 of each 21-day cycle for a total of 3 cycles.
Cisplatin is administered intravenously at a dose of 70 mg/m² on Day 1 of each 21-day cycle for a total of 3 cycles.
Peking University Third Hospital
Beijing, Beijing Municipality, China
RECRUITING1-Year Event-Free Survival (EFS) Rate
The percentage of participants who remain free of an event at 1 year. An event is defined as the first occurrence of any of the following: 1) radiographically confirmed disease progression during neoadjuvant therapy (per RECIST v1.1); 2) unresectable tumor or extensive pelvic metastasis identified during surgical exploration; 3) any type of local recurrence or distant metastasis (confirmed radiologically or pathologically) after radical surgery; 4) death from any cause.
Time frame: Up to 1 year post-surgery
Pathological Complete Response (pCR) Rate
The percentage of participants achieving a pathological complete response, defined as the absence of residual tumor in the bladder and lymph nodes (ypT0N0) upon postoperative pathological evaluation.
Time frame: At the time of radical surgery (Expected to be within 4-6 weeks after the last cycle of neoadjuvant therapy)
Pathological Downstaging Rate (pDR)
The percentage of participants achieving pathological downstaging, defined as pathological stage ≤ ypT1N0 upon postoperative pathological evaluation.
Time frame: At the time of radical surgery (Expected to be within 4-6 weeks after the last cycle of neoadjuvant therapy)
Disease-Free Survival (DFS)
The time from the date of radical surgery to the first documented local recurrence or distant metastasis (identified radiologically or pathologically), or death from any cause, whichever occurs first.
Time frame: From the date of radical surgery up to study completion (Assessed every 12 weeks for the first 48 weeks, then every 24 weeks, estimated up to 3 years)
Overall Survival (OS)
The time from the date of randomization to death from any cause.
Time frame: From the date of randomization up to study completion (Assessed every 12 weeks, estimated up to 3 years)
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Safety will be evaluated by the incidence, severity, and causality of AEs and SAEs. The severity of adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
Time frame: From the first dose of study drug up to 28 days after the last dose (or before starting new anti-tumor therapy, whichever is earlier)
Biomarker Expression: Nectin-4 and PD-L1
To evaluate the expression levels of Nectin-4 and PD-L1 in tumor tissue samples (obtained at baseline and post-surgery) and to analyze the relationship between these biomarker expressions and clinical efficacy.
Time frame: Baseline (Screening) and at the time of radical surgery
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