Study of Peripheral Neuropathy in Patients With Advanced Urothelial Cancer Treated With Enfortumab Vedotin and Pembrolizumab With Supportive Neuridase (ENDEAVOR) (ENDEAVOR)

ENDEAVOR Study: A Prospective Exploratory Study Describing the Course of Peripheral Neuropathy in Patients With Locally Advanced or Metastatic Urothelial Carcinoma Treated With Enfortumab Vedotin in Combination With Pembrolizumab and Supportive Neuridase

his prospective exploratory study aims to describe the course of peripheral neuropathy in patients with locally advanced or metastatic urothelial carcinoma treated with enfortumab vedotin in combination with pembrolizumab and receiving supportive Neuridase.

Peripheral neuropathy is a common adverse event associated with enfortumab vedotin and may negatively affect treatment tolerability, quality of life, and treatment continuation. Neuridase is a non-pharmacological supportive product intended to support peripheral nervous system function; however, its role in this clinical setting has not yet been established.

Participants enrolled in this single-arm study will receive standard-of-care treatment with enfortumab vedotin plus pembrolizumab, together with supportive Neuridase according to clinical practice. The study will prospectively assess neuropathy symptoms and severity using clinical evaluations and patient-reported outcome measures, including quality-of-life questionnaires, over the course of treatment.

The objective of the study is to explore neuropathy patterns and treatment tolerability in this patient population.

Study Overview

• Status: Not yet recruiting
• Conditions: Peripheral Nerve Disease; Urothelial Carcinoma (UC)
• Intervention / Treatment: Drug: enfortumab vedotin (EV); Drug: PEMBROLIZUMAB (alone or when added to a regimen above); Other: Neuridase

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lorenzo Antonuzzo, MD Phd, MD; Phone Number: 055-5465353; Email: lorenzo.antonuzzo@unifi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Age ≥18 years Histologically confirmed locally advanced or metastatic urothelial carcinoma Candidate for treatment with enfortumab vedotin in combination with pembrolizumab according to clinical practice Ability to provide written informed consent Adequate clinical conditions to participate in the study according to investigator judgment

Exclusion Criteria:

Pre-existing severe peripheral neuropathy that may interfere with study assessments Contraindications to enfortumab vedotin or pembrolizumab according to clinical practice Known hypersensitivity to components of Neuridase Pregnancy or breastfeeding Any medical, psychiatric, or social condition that, in the investigator's judgment, may interfere with study participation or interpretation of results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: arm label; Participants with locally advanced or metastatic urothelial carcinoma will receive standard-of-care enfortumab vedotin in combination with pembrolizumab together with supportive Neuridase according to the study protocol. Peripheral neuropathy symptoms, treatment tolerability, and patient-reported outcomes will be prospectively assessed during treatment.

Drug: enfortumab vedotin (EV); Standard-of-care enfortumab vedotin administered according to approved clinical practice.; Drug: PEMBROLIZUMAB (alone or when added to a regimen above); Standard-of-care pembrolizumab administered in combination with enfortumab vedotin according to approved clinical practice.; Other: Neuridase; Supportive non-pharmacological product administered during treatment with enfortumab vedotin and pembrolizumab to prospectively explore peripheral neuropathy trajectory, tolerability, and patient-reported outcomes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Peripheral Neuropathy	Incidence and severity of peripheral neuropathy will be prospectively assessed according to clinical evaluation and CTCAE criteria in patients receiving enfortumab vedotin plus pembrolizumab with supportive Neuridase.	From baseline to 6 months after treatment initiation

Collaborators and Investigators

• Sponsor: University of Florence
• Collaborators: Enfarma S.p.A.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: June 1, 2026
• First Submitted That Met QC Criteria: June 1, 2026
• First Posted (Actual): June 5, 2026

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Neuromuscular Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Peripheral Nervous System Diseases; Carcinoma, Transitional Cell; Socioeconomic Factors; Population Characteristics; Demography; Family Characteristics; Marital Status; pembrolizumab; enfortumab vedotin; Single Person
• Other Study ID Numbers: ENDEAVOR; CE 30693_spe (Registry Identifier: CE Careggi)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No