Circulating Tumor DNA Response In Urothelial Cancer

NCT07183319 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: OU-SCC-CT-READ
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this clinical trial is to evaluate the effectiveness of pembrolizumab monotherapy following 24 weeks of frontline pembrolizumab \& Enfortumab Vedotin (PEV) in patients with metastatic urothelial cancer (mUC).

Conditions

Urothelial Carcinoma

Keywords

Metastatic; ctDNA; Pembrolizumab; De-escalation therapy

Outcome Measures

Primary Outcomes (2)

• 3 months of progression-free survival (PFS) while on Pembrolizumab Monotherapy.

  Number of patients who achieve PFS at the 3-month mark on pembrolizumab monotherapy. These patients will undergo radiographic assessments to evaluate progression-free survival (PFS).

  3 months

• 6 months of PFS while on Pembrolizumab Monotherapy

  Number of patients in the de-escalation phase who have reached 6-month PFS while on pembrolizumab monotherapy.

  6 months

Secondary Outcomes (4)

• Treatment Related Adverse Events (TRAEs) while on Pembrolizumab Monotherapy.

  1 year

• Pain Assessment In Patients While On Pembrolizumab Monotherapy.

  1 year

• Changes In Peripheral Neuropathy While on Pembrolizumab Monotherapy

  1 year

• Health Assessment In Patients While On Pembrolizumab Monotherapy

  1 year

Study Arms (1)

Pembrolizumab & Enfortumab Vedotin (PEV)

EXPERIMENTAL

Patients with metastatic urothelial carcinoma (mUC) will initiate first-line (1L) PEV therapy as the standard of care. At 24 weeks, radiographic imaging will be performed to evaluate disease status. Patients who exhibit either stable disease or ongoing radiographic response, accompanied by a ≥50% reduction in circulating tumor DNA (ctDNA) levels, will transition to pembrolizumab monotherapy as part of a treatment de-escalation strategy. Pembrolizumab will be continued until the occurrence of disease progression or unacceptable toxicity. In the event of progression or intolerance, patients will be re-challenged with first-line PEV therapy and continue treatment until completion of the study-defined treatment period.

Drug: Pembrolizumab & Enfortumab Vedotin (PEV); Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Patients will receive 400 mg of pembrolizumab every 42 days. During the de-escalation period from PEV.

Also known as: KEYTRUDA

Pembrolizumab & Enfortumab Vedotin (PEV)

Pembrolizumab & Enfortumab Vedotin (PEV) DRUG

Patients in the study will receive 1L PEV with 1.25 mg/kg of EV on day 1 and day 8 every 21 days, and 200 mg of pembrolizumab every 21 days.

Also known as: PADCEV

Pembrolizumab & Enfortumab Vedotin (PEV)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have histologically documented unresectable, locally advanced, or metastatic urothelial carcinoma.
• Measurable disease according to the New Response Evaluation Criteria in Solid Tumors (RECIST v1.1)38
• a. Participants with prior definitive radiation therapy must have measurable disease per RECIST v1.1 that is outside the radiation field or has demonstrated unequivocal progression since completion of radiation therapy.
• Must be considered eligible to receive cisplatin- or carboplatin-containing chemotherapy, in the investigator's judgment.
• Archival tumor tissue comprising muscle-invasive urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma must be available for tumor-informed ctDNA analysis.
• Meets Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2.
• Adequate hematologic and organ function (Hb ≥ 8.0 g/dL; ANC ≥ 1.5x109 cells/L; CrCl \~30 mL/min; total bilirubin ≤ 1.5 mg/dL; ALT and AST within normal limits).

You may not qualify if:

• Previously received enfortumab, vedotin, or other monomethyl auristatin E (MMAE)-based ADCs.
• Received prior treatment with a programmed cell death ligand-1 (PD-(L)-1) inhibitor for any malignancy, including earlier stage UC, defined as a PD-1 inhibitor or PD-L1 inhibitor within 12 months.
• Has uncontrolled diabetes or ≥ grade III peripheral neuropathy.
• Patient's estimated life expectancy is less than 12 weeks.
• Has untreated central nervous system metastases.
• Experiences ongoing clinically significant toxicity associated with prior treatment that has not resolved to ≤ Grade 1 or returned to baseline.
• Is currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal). Routine antimicrobial prophylaxis is permitted.
• Has known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection.
• Has history of another invasive malignancy requiring treatment within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy (excluding localized prostate cancer or basal cell carcinoma of skin or squamous cell carcinoma of the skin).
• Has documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class IV within 6 months.
• Received radiotherapy within 2 weeks.
• Received major surgery (defined as requiring general anesthesia and \>24-hour inpatient hospitalization) within 2 weeks.
• Known severe (≥ Grade 3) hypersensitivity to any EV excipient contained in the drug formulation of EV.
• Has active keratitis or corneal ulcerations.
• Has a history of autoimmune disease that has required systemic immunosupressive treatment in the past 2 years, or uncontrolled autoimmune disease.

Sponsors & Collaborators

• University of Oklahoma: lead
• Natera, Inc.: collaborator

Study Sites (1)

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, 73117, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Neoplasm Metastasis

Interventions

pembrolizumab; enfortumab vedotin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Adanma Ayanambakkam, MD

  University of Oklahoma

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lead Onco Nurse

CONTACT

405-271-8777; SCC-IIT-Office@ouhsc.edu

Adanma Ayanambakkam, MD

CONTACT

405-271-4022; Adanma-Ayanambakkam@ouhsc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a single-arm, open-label pilot trial evaluating de-escalation of therapy in patients with reduction in ctDNA following 1L Pembrolizumab \& Enfortumab Vedotin (PEV) for Metastatic Urothelial Carcinoma (mUC).

Study Record Dates

• First Submitted: September 2, 2025
• First Posted: September 19, 2025
• Study Start: January 19, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: February 2, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)