A Phase 2 interventional study of enfortumab vedotin and pembrolizumab (EV/P) in Urothelial Carcinoma (UC), sponsored by University of Florida. Not yet recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-14.
Sponsored by University of Florida · Phase 2, Interventional, and Treatment
Radical cystectomy remains the standard curative-intent treatment for most patients with muscle-invasive bladder cancer, but it is associated with significant morbidity and long-term quality-of-life implications. Trimodality therapy is an accepted standard-of-care alternative for carefully selected patients who wish to preserve their bladder; however, optimal patient selection remains challenging.
The combination of enfortumab vedotin plus pembrolizumab (EV-P) has demonstrated remarkable activity in urothelial carcinoma, including in the perioperative setting, with pathologic complete response rates of approximately 50-60%. These results generate the hypothesis that a subset of patients may achieve sufficiently deep responses to allow selective deferral of cystectomy. Cohort A of this trial prospectively evaluates the use of multimodal response assessment (pelvic MRI and TURBT, ctDNA) to guide individualized decisions regarding cystectomy versus bladder preservation.
Radical nephroureterectomy (RNU) remains the standard curative-intent treatment for high-risk upper tract urothelial carcinoma (UTUC), but recurrence rates after surgery alone are high. Neoadjuvant cisplatin-based chemotherapy improves pathologic outcomes and is supported by phase II data, but its delivery is constrained by baseline renal dysfunction and the further decline in glomerular filtration that follows RNU - historically, only about 20% of patients remain cisplatin-eligible postoperatively, which is the principal rationale for delivering platinum in the neoadjuvant rather than adjuvant setting. A large fraction of patients with UTUC are cisplatin-ineligible at baseline, and no level 1 evidence supports a specific neoadjuvant regimen in this population.
EV-P is not constrained by renal function and has produced unprecedented activity in urothelial carcinoma. In the EV-302 upper tract subgroup, EV-P achieved an objective response rate of 67.7% and a complete response rate of 28.6%, with survival benefit preserved relative to platinum-based chemotherapy. In the perioperative bladder cancer setting, EV-P has yielded pathologic complete response rates of approximately 50-60%. However, available data on EV-P in UTUC are restricted to the metastatic setting, and prospective evaluation in the neoadjuvant setting is lacking. Cohort B of this trial addresses this gap by prospectively evaluating neoadjuvant EV-P followed by RNU in patients with high-risk UTUC, with pathologic complete response as the primary endpoint.
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This study's planned enrollment of 39 is below the median of 50 across 500 interventional studies indexed under Carcinoma, Transitional Cell.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
For Cohort B, a clinical or pathological diagnosis of upper tract urothelial carcinoma, with high-intermediate risk or higher per NCCN guidelines, planned for definitive surgery.
High: High grade + Multifocal or >1.5 cm or high-grade renal obstruction or invasion on axial imaging Any proportion of divergent differentiation is permitted across all histologies (except neuroendocrine - see exclusion criteria), as long as a urothelial component is identified.
Note: Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the regimen or primary endpoint (as determined by the treating physician) are eligible for this trial.
- Subjects of (SOCBP) must be using an adequate method of to avoid pregnancy throughout the study and for at least 4 months after the last dose of EV-P to minimize the risk of pregnancy. Prior to study enrollment, subjects of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.
SOCBP includes any subject who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who is not . Post-menopause is defined as:
For subjects with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Following neoadjuvant EV-P, participants in this cohort will have response-adapted management based on if they achieved a composite clinical complete response (cCR) to determine the next step in their treatment on this study. A participant has achieved cCR if ALL the following are met: 1. ctDNA is negative, 2. Imaging are negative for lymph nodes and distant metastases, and 3. TURBT shows T0 or Ta low-grade only, and a negative urinary cytology. If a participant achieves cCR, they will have a choice between: * receive 5 more cycles of EV-P, followed by pembrolizumab alone to complete 1 year of therapy. * Alternatively, if participant wishes, partial or radical cystectomy. If a participant does not achieve cCR, they will have cystectomy.
Drug: enfortumab vedotin and pembrolizumab (EV/P)
Drug: enfortumab vedotin and pembrolizumab (EV/P)
Participants in both cohorts will first receive neoadjuvant enfortumab vedotin + pembrolizumab (EV-P) for 4 cycles. Each cycle is 21 days. Participants will be given 1.25 mg/kg enfortumab vedotin intravenously on days 1 and 8 and 200 mg pembrolizumab intravenously on day 1 of each cycle. Participants in Cohort A may then choose to receive 5 more cycles of EV-P followed by pembrolizumab alone to complete 1 year of study therapy if they have a composite complete clinical response. Participants in Cohort B will then receive 5 more cycles of EV-P followed by pembrolizumab alone to complete 1 year of study therapy following their definitive surgery.
This study also gives Pembrolizumab, Enfortumab vedotin. No intervention listed here names it: that was found by reading the record.
Clinical complete response rate
Determine the percent of subjects in Cohort A that achieve a clinical complete response following completion of neoadjuvant EV-P. A clinical complete response is defined as having all three of the following: * A negative ctDNA result, * Imaging of the pelvis with negative lymph nodes and no distant metastasis on CT scans, AND * A TURBT showing T0 or low-grade Ta only, and a negative urinary cytology.
Time frame: 3 weeks following completion of neoadjuvant therapy
Pathologic complete response rate
Determine the percent of subjects in Cohort B who achieve a pathologic complete response at the time of surgery. A pathologic complete response is defined as having disease staging of pT0N0 at time of surgery.
Time frame: 8 weeks following completion of neoadjuvant therapy
Event-free survival
Determine the event-free survival of patients in Cohort A at 1 year from the start of EV-P
Time frame: 1 year from the start of EV-P
Event-free survival
Determine the event-free survival of patients in Cohort A at 2 years from the start of EV-P
Time frame: 2 years from the start of EV-P
Overall survival
Determine the overall survival of patients in Cohort A at 1 year from the start of EV-P
Time frame: 1 year from the start of EV-P
Overall survival
Determine the overall survival of patients in Cohort A at 2 years from the start of EV-P
Time frame: 2 years from the start of EV-P
Bladder-intact survival
Determine the bladder-intact survival of patients in Cohort A at 1 year from the start of EV-P
Time frame: 1 year from the start of EV-P
Bladder-intact survival
Determine the bladder intact survival of patients in Cohort A at 2 years from the start of EV-P
Time frame: 2 years from the start of EV-P
Pathological complete response
Determine number of subjects in cohort A who achieve a pathological complete response after first 4 cycles of EV-P.
Time frame: After completion of first 4 cycles of EV-P (each cycle of EV-P is 21 days)
Pathologic downstaging
Determine number of patients in cohort A who achieve pathological downstaging (disease staging \<pT2N0) after the first 4 cycles of EV-P
Time frame: At completion of first 4 cycles of EV-P (each cycle of EV-P is 21 days)
Event-free survival
Determine the event-free survival of patients in Cohort B at 2 years from the start of EV-P
Time frame: 2 years from the start of EV-P
Overall survival
Determine the overall survival of patients in Cohort B at 2 years from the start of EV-P
Time frame: 2 years from the start of EV-P
Pathologic downstaging
Determine number of patients in cohort B who achieve pathological downstaging (disease staging \<pT2N0) after the first 4 cycles of EV-P
Time frame: At completion of first 4 cycles of EV-P (each cycle of EV-P is 21 days)
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This study is not yet recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Pembrolizumab · Enfortumab vedotin
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