Status:
RECRUITING
Circulating Tumor DNA Response In Urothelial Cancer
Lead Sponsor:
University of Oklahoma
Collaborating Sponsors:
Natera, Inc.
Conditions:
Urothelial Carcinoma
Eligibility:
All Genders
18+ years
Phase:
PHASE2
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 u...
Detailed Description
This study aims to evaluate the de-escalation of therapy in patients with metastatic urothelial carcinoma (mUC). Patients will begin treatment with first-line (1L) (PEV) per standard of care. After 24...
Eligibility Criteria
Inclusion
- 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).
Exclusion
- 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 received anti-cancer treatment with chemotherapy, biologics, or investigational agents not otherwise prohibited by exclusion criterion 1-3 that is not completed within 28 days prior to cycle 1 day 1.
- 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.
- Participants must not have received prior systemic therapy for locally advanced or metastatic urothelial carcinoma with the following exceptions:
- Participants that received neoadjuvant chemotherapy with recurrence \>12 months from completion of therapy are permitted.
- Participants that received adjuvant chemotherapy or ICPIs therapy following cystectomy with recurrence \>12 months from completion of therapy are permitted.
- Has a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
- Has received prior allogeneic stem cell or solid organ transplant.
- Received a live attenuated vaccine within 30 days.
Key Trial Info
Start Date :
December 1 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
March 1 2029
Estimated Enrollment :
30 Patients enrolled
Trial Details
Trial ID
NCT07183319
Start Date
December 1 2025
End Date
March 1 2029
Last Update
December 4 2025
Active Locations (1)
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1
OU Health Stephenson Cancer Center
Oklahoma City, Oklahoma, United States, 73117