eligibility_summary
Eligible: adults ≥18 with histologically confirmed metastatic or unresectable locally advanced urothelial carcinoma, no prior systemic therapy for laUC/mUC, and able to receive enfortumab vedotin plus pembrolizumab. Exclude: contraindications to either drug, any prior systemic treatment for laUC/mUC, prior EV, other MMAE-ADCs, or PD-(L)1 inhibitors, neoadjuvant/adjuvant platinum within 12 months.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
P-EVOLUTION (NCT06657157) is a prospective, multicenter, non-interventional study in treatment‑naïve metastatic/locally advanced urothelial carcinoma patients receiving first-line enfortumab vedotin (EV) plus pembrolizumab, assessing incidence/severity of peripheral neuropathy, quality of life, and treatment modifications (~80 patients, Germany). Drugs/mechanisms: Enfortumab vedotin is a Nectin-4–directed antibody-drug conjugate (IgG1 mAb linked to MMAE), delivering a microtubule inhibitor that disrupts tubulin, causing cell-cycle arrest and apoptosis, MMAE exposure is associated with peripheral neuropathy. Pembrolizumab is an anti–PD-1 IgG4 checkpoint inhibitor mAb that blocks PD-1/PD-L1/PD-L2 interactions, restoring T-cell activation. Targets: Nectin-4–expressing tumor cells, microtubules/tubulin, PD-1–positive T cells and the PD-1/PD-L1 pathway in the tumor microenvironment.