EV + Toripalimab vs GC as Neoadjuvant Therapy in Locally Advanced/High-Risk MIBC
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-80
SponsorPeking University Third Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Voluntarily agree to participate in the study and sign the informed consent form (ICF).
Age ≥ 18 and ≤ 80 years at the time of signing the ICF.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Histologically confirmed muscle-invasive urothelial carcinoma of the bladder, with variant histology components comprising < 50%.
Disqualifiers
Prior systemic anti-tumor therapy for urothelial carcinoma, including radiotherapy, chemotherapy, targeted therapy, or biological therapy (except for intravesical instillation therapy).
Prior treatment with PD-1/PD-L1 inhibitors or antibody-drug conjugates (ADCs).
Active malignancies other than urothelial carcinoma within 3 years prior to the first dose, except for curatively treated malignancies (e.g., basal or squamous cell skin cancer, localized low-risk prostate cancer, papillary thyroid cancer, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast).
Active autoimmune disease requiring systemic treatment (e.g., use of disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years prior to the first dose; or received high-dose steroids (>10 mg/day prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose. (Physiological replacement therapies are permitted).
Trial design
Design model
Parallel
Treatments tested in this trial
enfortumab vedotin (EV)
DrugEnfortumab 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
DrugToripalimab is administered intravenously at a dose of 240 mg on Day 1 of each 21-day cycle for a total of 3 cycles.
Gemcitabine (Chemotherapy)
DrugGemcitabine 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
DrugCisplatin is administered intravenously at a dose of 70 mg/m² on Day 1 of each 21-day cycle for a total of 3 cycles.
Treatment groups
58 Participants
are divided into 2 treatment groupsGroup A: Experimental: Enfortumab Vedotin + ToripalimabExperimental treatment 2 interventions
Group B: Active Comparator: Gemcitabine + CisplatinActive comparator 2 interventions
Trial outcomes
Primary outcomes
1
1-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-surgerySecondary outcomes
1
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)2
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)3
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)4
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)Other outcomes
1
Patient-Reported Outcomes (PROs)
Patient-reported general cancer quality of life is assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). The EORTC QLQ-C30 is a validated 30-item questionnaire incorporating a Global Health Status/Quality of Life scale, 5 functional scales (physical, role, emotional, cognitive, and social), and multiple symptom scales. All scale scores are linearly transformed to range from 0 to 100. For the Global Health Status and functional scales, higher scores indicate better quality of life or higher functioning. For symptom scales and items, higher scores indicate greater symptom burden.
Time frame
From baseline up to study completion (Estimated up to 36 months)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Peking University Third Hospital
Lead sponsor
Jiangsu Provincial People's Hospital
Collaborator
Peking University Cancer Hospital & Institute
Collaborator
Source ClinicalTrials.gov