A Biomarker Study to Predict Treatment Outcomes of Enfortumab Vedotin in Advanced Urothelial Carcinoma

NCT07063758 | Active Not Recruiting

• 1 other identifier: 202502065RINE
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to find biological markers that help predict how patients with advanced urothelial carcinoma respond to treatment with enfortumab vedotin (EV) or EV-based combination therapies. Since EV can cause significant side effects and is costly, identifying markers such as nectin-4 and related proteins in tumor tissue and blood may help doctors personalize treatment plans. The investigators will enroll about 100 patients receiving EV and compare them to another 100 patients treated with standard chemotherapy. By studying tissue samples and blood at different times, the investigators hope to discover which markers best indicate treatment success or risks. This research could lead to better, safer treatments tailored to each patient's biology.

Conditions

Advanced Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Proportion of patients achieving complete or partial tumor response according to RECIST 1.1 criteria after enfortumab vedotin treatment.

  Up to 12 months after treatment initiation

Secondary Outcomes (4)

• Progression-Free Survival (PFS)

  Up to 24 months

• Overall Survival (OS)

  Up to 36 months

• Treatment-Related Adverse Events

  Up to 36 months

• Association of Nectin-4, ADAM10/17 Expression and Serum Soluble Nectin-4 with Overall Survival, Progression-Free Survival, Objective Response Rate, and Adverse Events

  Assessed at baseline and up to 36 months

Study Arms (2)

EV Therapy Cohort

Patients with advanced urothelial carcinoma who receive enfortumab vedotin-based therapies. Tumor tissue and serum samples will be collected and analyzed for membranous Nectin-4, ADAM10/17, and soluble Nectin-4 (sNectin-4) to assess their association with treatment outcomes.

Other: Biomarker Analysis

Chemotherapy Cohort

Patients with advanced urothelial carcinoma who receive platinum-based chemotherapy. Tumor tissue and serum samples will be collected and analyzed for membranous Nectin-4, ADAM10/17, and soluble Nectin-4 (sNectin-4) to assess their association with treatment outcomes.

Other: Biomarker Analysis

Interventions

Biomarker Analysis OTHER

Tumor tissue and serum samples will be collected and analyzed to evaluate the expression of membranous Nectin-4, ADAM10/17, and levels of soluble Nectin-4 (sNectin-4) as predictive biomarkers in patients with advanced urothelial carcinoma receiving standard therapies.

Chemotherapy Cohort; EV Therapy Cohort

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with advanced urothelial carcinoma receiving enfortumab vedotin-based therapies or first-line platinum-based chemotherapy. Participants will be adults aged 20 years or older, of any sex, with available archival tumor tissue and serum samples for biomarker analyses. Patients must have adequate organ function and no prior treatment with enfortumab vedotin.

You may qualify if:

• Age ≥ 20 y/o
• Histologically confirmed urothelial carcinoma
• Radiologically documented locally advanced or metastatic disease
• Exposure to EV (as monotherapy or in combination with pembrolizumab) or first-line platinum-based chemotherapy
• Complete and identifiable medical records

You may not qualify if:

• Inadequate or insufficient tumor tissues for analyses
• Incomplete medical records

Sponsors & Collaborators

• National Taiwan University Clinical Trial Center: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, Taiwan

Location

Related Publications (1)

• Powles T, Valderrama BP, Gupta S, Bedke J, Kikuchi E, Hoffman-Censits J, Iyer G, Vulsteke C, Park SH, Shin SJ, Castellano D, Fornarini G, Li JR, Gumus M, Mar N, Loriot Y, Flechon A, Duran I, Drakaki A, Narayanan S, Yu X, Gorla S, Homet Moreno B, van der Heijden MS; EV-302 Trial Investigators. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer. N Engl J Med. 2024 Mar 7;390(10):875-888. doi: 10.1056/NEJMoa2312117.

  PMID: 38446675 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples and peripheral blood samples (serum) will be retained. Tumor tissues will be used for immunohistochemical analysis of membranous Nectin-4 and ADAM10/17 expression. Serum samples will be collected at predefined time points during treatment to measure soluble Nectin-4 (sNectin-4) levels. Samples may also be used in future biomarker studies, including DNA-based analyses.

Study Officials

• Fu-Jen Hsueh, M.D.

  Department of Medical Oncology, National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: National Taiwan University Hospital Clinical Trial Center

Study Record Dates

• First Submitted: June 24, 2025
• First Posted: July 14, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: July 16, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

TW (1)