A Prospective Study Assessing Neurological Function and Its Clinical Implications in Patients With Locally Advanced or Metastatic Urothelial Carcinoma Receiving Enfortumab Vedotin-Based Therapy
Conditions: Locally Advanced or Metastatic Urothelial Carcinoma
Sponsor: National Taiwan University Hospital

Official Study Title 
A Prospective Study Assessing Neurological Function and Its Clinical Implications in Patients 
With Locally Advanced or Metastatic Urothelial Carcinoma Receiving Enfortumab Vedotin-
Based Therapy 
 
ClinicalTrials.gov Identifier (NCT Number): Pending Assignment 
Document Date: June 27, 2025 
 
Confidentiality Notice: 
This document is intended for use in the ClinicalTrials.gov registration and results reporting 
process only. It does not contain any personal identifiers of study participants. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
1. Official Study Title 
A Prospective Study Assessing Neurological Function and Its Clinical Implications in Patients With 
Locally Advanced or Metastatic Urothelial Carcinoma Receiving Enfortumab Vedotin-Based Therapy 
 
2. Background and Rationale 
Locally advanced or metastatic urothelial carcinoma (la/mUC) remains a highly lethal disease despite 
advances in systemic therapy. While platinum-based chemotherapy (Plt-ChT) has long been the 
mainstay of first-line treatment, its survival benefit is limited by significant toxicity and a lack of 
durable response. Enfortumab vedotin (EV) is a NECTIN-4-directed antibody-drug conjugate (ADC) that 
has demonstrated robust antitumor activity in patients with la/mUC. In the phase III EV-301 study, EV 
significantly improved overall survival in patients who progressed following Plt-ChT and ICIs. More 
recently, the phase III EV-302 trial established EV in combination with pembrolizumab as a superior 
first-line therapy compared to Plt-ChT, regardless of cisplatin eligibility. Based on these data, EV has 
been approved in both first-line (in combination) and third-line (monotherapy) settings and is 
considered a standard of care in la/mUC. 
However, peripheral neuropathy (PN), a known adverse event associated with the payload 
monomethyl auristatin E (MMAE), remains a major dose-limiting toxicity of EV. PN occurs in 40–50% of 
patients, can be irreversible, and significantly impairs patients’ quality of life. Although the underlying 
mechanisms are not fully elucidated, they may include both on-target and off-target effects, such as 
MMAE-induced microtubule disruption, premature drug release, and neuroinflammatory processes. 
Notably, the lack of objective tools for early identification and quantitative monitoring of EV-induced 
PN poses a clinical challenge. 
This study aims to prospectively assess neurological function in patients receiving EV-based therapy for 
la/mUC. By correlating objective neurological assessments with patient-reported outcomes, we seek 
to improve the understanding of EV-related PN, identify high-risk individuals, and lay the groundwork 

for future preventive or mitigating strategies. The findings may ultimately contribute to optimizing EV-
based treatment by balancing efficacy with tolerability. 
 
3. Objectives 
3-1. Primary Objective 
(1) To investigate the correlation between neurological function and subjective symptoms of PN during 
EV-based therapy. 
3-2. Secondary Objectives 
(1) To evaluate the relationship between patient characteristics/neurological function changes and 
patient-reported PN in order to identify high risk patients for developing PN during EV-based 
therapy. 
(2) To investigate the correlation between neurological function changes and oncological outcomes of 
EV-based therapy, including objective response rate (ORR), progression-free survival (PFS), and 
overall survival (OS). 
 
4. Study Design 
4-1. Study Type: Observational 
4-2. Study Design: Prospective cohort study 
4-3. Study Center: Single-center (National Taiwan University Hospital, NTUH); may expand to  
multi-center in the future 
4-4. Enrollment Method: Consecutive enrollment of eligible patients 
4-5. Study Period: July, 2025 to December 31, 2031 

4-6. Estimated Sample Size: 100 patients receiving EV-based therapy 
 
5. Study Population 
5-1. Inclusion Criteria 
(1) Age ≥ 20 y/o 
(2) Histologically confirmed urothelial carcinoma 
(3) Radiologically documented locally advanced or metastatic disease 
(4) Prepare for receiving EV (as monotherapy or in combination with immune checkpoint inhibitors)  
(5) Complete and identifiable medical records 
   5-2. Exclusion Criteria 
(1) Do not agree to receive regular neurological examinations  
(2) Do not agree to provide complete medical records during treatment 
5-3. Sampling Method 
(1) Consecutive enrollment of eligible patients meeting the inclusion criteria 
 
6. Study Groups/Cohorts 
6-1. Group 1: EV-based Therapy Cohort 
(1) Population: Patients with locally advanced or metastatic urothelial carcinoma receiving  
EV-based therapy 
(2) Diagnostic test: Neurological evaluations including neurological examination (NE), nerve 
conduction study (NCS), quantitative sensory testing (QST), autonomic function testing (AFT), and 
the Toronto Clinical Neuropathy Score (TCNS) questionnaire. Assessments will be conducted at 
baseline and every three months until six months after completion of EV treatment.  

 
7. Endpoints / Outcome Measures 
7-1. Primary Outcome Measure 
(1) Correlation between neurological function and subjective PN symptoms: 
Correlation between objective neurological assessments (including NE, QST, AFS, and TCNS) and 
patient-reported PN symptoms.  
Time Frame: Baseline to 6 months post-treatment. 
7-2. Secondary Outcome Measure 
  (1)  Correlation between neurological function changes and oncological outcomes: To evaluate 
whether the degree or pattern of neurological function changes (e.g., worsening in NCS, QST) 
correlates with clinical efficacy measures such as ORR, PFS, and OS. 
Time Frame: From date of EV initiation to the date of death from any cause, assessed up to 36 
months 
 
8. Methods / Assessments 
8-1. Neurological assessment 
(1) NE 
(2) NCS 
(3) QST 
(4) AFT 
(5) TCNS  
    All of these neurological function assessment will be evaluated as baseline , every three month 
during treatment, up to 6 months after completion of treatment. 

8-2. Data Collection 
Demographic, clinical, and treatment-related data will be recorded, including age, sex, comorbidities, 
ECOG performance status, prior treatments, EV regimen details, and cumulative dose. Patient-
reported outcomes (PN symptoms) and oncological outcomes (ORR, PFS, OS) will also be collected.  
8-3. Statistical Analysis 
(1) Descriptive statistics will be used to summarize patient characteristics. 
(2) Survival analysis: 
o Kaplan–Meier method for estimating PFS and OS 
o Log-rank test for between-group comparisons 
(4) Multivariable analysis: 
o Cox proportional hazards model to assess the independent association of neurological function  
factors with survival outcomes 
o Logistic regression for associations with objective response 
 
9. Ethics / Regulatory Compliance 
9-1. The study protocol has been reviewed and approved by the Research Ethics Committee B of 
National Taiwan University Hospital. 
IRB Approval Number:202502005RINB 
Approval Date: 2025-03-13 
9-2. This study will be conducted in accordance with the principles of the Declaration of Helsinki, ICH 
Good Clinical Practice (GCP) guidelines, and applicable local regulatory requirements. 
9-3. Informed consent will be obtained from all participants before enrollment. The consent process will 
include information on study purpose, procedures, risks, benefits, data confidentiality, and the 
voluntary nature of participation. 

9-4. Confidentiality and data protection: 
(1) All personal identifying information will be coded and stored securely in password-protected 
databases. 
(2) Only authorized study personnel will have access to identifiable data. 
(3) Data will be reported in aggregate to prevent the identification of individual participants. 
 
10. Study Timeline 
 10-1. Planned Study Start Date: Jul, 2025 
 10-2. Planned Study End Date (Final Data Collection): December 31, 2031 
 10-3. Primary Completion Date: December 31, 2030 
 10-4. Study Completion Date: December 31, 2031