Urothelial CarcinomaPhase 2NCT07183319
Circulating Tumor DNA Response In Urothelial Cancer
A Phase 2 study testing Pembrolizumab & Enfortumab Vedotin (PEV) and Pembrolizumab in people with Urothelial Carcinoma, run by University of Oklahoma at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Carcinoma
- What is being tested?
- Pembrolizumab & Enfortumab Vedotin (PEV) and Pembrolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Jan 2026to Mar 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- 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).
Who cannot join
- 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.
Show all 22Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
OU Health Stephenson Cancer Center
Oklahoma City, Oklahoma, 73117
Adanma Ayanambakkam, MD, 405-271-4022, Adanma-Ayanambakkam@ouhsc.edu
About this study
Official title: Circulating Tumor DNA Response Adapted Treatment De-escalation Metastatic Urothelial Carcinoma (CT-READ)
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).
Read the 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 weeks, patients will be assessed for disease progression. Those who demonstrate stable disease or ongoing disease radiographic response and a ≥50% reduction in circulating tumor DNA (ctDNA) levels will enter the de-escalation phase. This phase consists of transitioning from PEV to pembrolizumab monotherapy. If, during the de-escalation period, patients exhibit disease progression or increased toxicity, they will be rechallenged with PEV.
- Conditions
- Urothelial Carcinoma
- Being tested
- Pembrolizumab & Enfortumab Vedotin (PEV), Pembrolizumab
- Keywords
- Metastatic, ctDNA, Pembrolizumab, De-escalation therapy
- Medical subject headings
- Carcinoma, Transitional Cell, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab & Enfortumab Vedotin (PEV)Drug
Also called PADCEV
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.
PembrolizumabDrug
Also called KEYTRUDA
Patients will receive 400 mg of pembrolizumab every 42 days. During the de-escalation period from PEV.
Pembrolizumab & Enfortumab Vedotin (PEV)Drug
Also called PADCEV
If patients experience radiographic progression on pembrolizumab monotherapy, they will undergo rechallenge with PEV.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Pembrolizumab & Enfortumab Vedotin (PEV); Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 6 months
Secondary outcomes (4)
Treatment Related Adverse Events (TRAEs) while on Pembrolizumab Monotherapy.
Number of patients who experience treatment-related adverse events (TRAEs) while in the de-escalation phase treated with pembrolizumab monotherapy following 1L PEV. Any adverse events (AEs) or TRAEs that do occur will be assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measured: 1 year
Pain Assessment In Patients While On Pembrolizumab Monotherapy.
The Brief Pain Inventory (BPI) questionnaire will be administered to assess participants' perceived pain levels. Pain intensity will be rated on a Likert scale ranging from 0, indicating no pain, to 10, representing the most severe and unimaginable pain.
Measured: 1 year
Changes In Peripheral Neuropathy While on Pembrolizumab Monotherapy
The Functional Assessment of Cancer Therapy-Neurotoxicity 12 (FACT-NTX-12) will be administered every 12 weeks to evaluate peripheral neuropathy. This tool measures quality of life in relation to neuropathy symptoms, vibration perception threshold, and extension strength testing. Responses are rated on a 5-point Likert scale, ranging from 0 ("not at all") to 4 ("very much").
Measured: 1 year
Health Assessment In Patients While On Pembrolizumab Monotherapy
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) will be administered to assess participants' quality of life, including physical, emotional, and social functioning, as well as cancer-related symptoms. Responses are measured on a Likert scale from 1 ("not at all") to 4 ("very much").
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2025
- Study start19 Jan 2026
- Primary completionMar 2028 (estimated)
- Study completionMar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by University of OklahomaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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).
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oklahoma
- Sponsor type
- University, hospital or other
- Collaborators
- Natera, Inc.
- Responsible party
- Sponsor
- Investigators
- Adanma Ayanambakkam, MD, Principal investigator, University of Oklahoma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07183319
- Sponsor's protocol ID
- OU-SCC-CT-READ
- Status last verified
- Jan 2026
- First submitted
- 2 Sep 2025
- Last updated
- 2 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Circulating Tumor DNA Response Adapted Treatment De-escalation Metastatic Urothelial Carcinoma (CT-READ)
- ClinicalTrials.gov ID
- NCT07183319
- Acronym / sponsor ID
- OU-SCC-CT-READ
- Conditions
- Urothelial Carcinoma
- Keywords
- Metastatic, ctDNA, Pembrolizumab, De-escalation therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of OklahomaUniversity, hospital or other
- Collaborators
- Natera, Inc.
- Study start
- 19 Jan 2026 (actual)
- Primary completion
- Mar 2028 (estimated)
- Study completion
- Mar 2029 (estimated)
- First posted
- 19 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 weeks, patients will be assessed for disease progression. Those who demonstrate stable disease or ongoing disease radiographic response and a ≥50% reduction in circulating tumor DNA (ctDNA) levels will enter the de-escalation phase. This phase consists of transitioning from PEV to pembrolizumab monotherapy. If, during the de-escalation period, patients exhibit disease progression or increased toxicity, they will be rechallenged with PEV.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab & Enfortumab Vedotin (PEV) | Experimental | Drug: Pembrolizumab & Enfortumab Vedotin (PEV), Drug: PembrolizumabPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
- 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.
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pembrolizumab & Enfortumab Vedotin (PEV)Also: PADCEVPatients 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. | Drug | Pembrolizumab & Enfortumab Vedotin (PEV) |
| PembrolizumabAlso: KEYTRUDAPatients will receive 400 mg of pembrolizumab every 42 days. During the de-escalation period from PEV. | Drug | Pembrolizumab & Enfortumab Vedotin (PEV) |
| Pembrolizumab & Enfortumab Vedotin (PEV)Also: PADCEVIf patients experience radiographic progression on pembrolizumab monotherapy, they will undergo rechallenge with PEV. | Drug | Pembrolizumab & Enfortumab Vedotin (PEV) |
Primary outcome
3 months of progression-free survival (PFS) while on Pembrolizumab Monotherapy.
Time frame: 3 months
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).
6 months of PFS while on Pembrolizumab Monotherapy
Time frame: 6 months
Number of patients in the de-escalation phase who have reached 6-month PFS while on pembrolizumab monotherapy.
4 secondary outcomes
Treatment Related Adverse Events (TRAEs) while on Pembrolizumab Monotherapy.
Time frame: 1 year
Pain Assessment In Patients While On Pembrolizumab Monotherapy.
Time frame: 1 year
Changes In Peripheral Neuropathy While on Pembrolizumab Monotherapy
Time frame: 1 year
Health Assessment In Patients While On Pembrolizumab Monotherapy
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Adanma Ayanambakkam, MD principal investigator
University of Oklahoma
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab & Enfortumab Vedotin (PEV) and Pembrolizumab in people with Urothelial Carcinoma, run by University of Oklahoma at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lead Onco Nurse (405-271-8777, SCC-IIT-Office@ouhsc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3 months of progression-free survival (PFS) while on Pembrolizumab Monotherapy. (time frame: 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2026.