Urothelial Carcinoma (UC)Phase 2NCT07643519
Neoadjuvant Enfortumab Vedotin Plus Pembrolizumab in Muscle-Invasive Bladder Cancer and Upper Tract Urothelial Carcinoma
A Phase 2 study testing enfortumab vedotin and pembrolizumab (EV/P) in people with Urothelial Carcinoma (UC), run by University of Florida.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Carcinoma (UC)
- What is being tested?
- enfortumab vedotin and pembrolizumab (EV/P)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- No sites listed yet
- Study dates
- Dec 2026to Oct 2030
- 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
- Adults ≥ 18 years of age.
- ECOG Performance Status of 0-2
- For Cohort A, a clinical or pathological diagnosis consistent with muscle-invasive urothelial carcinoma of the bladder (locoregional), with a clinical staging of T2 or higher, N0 to N2, and M0.
- 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-intermediate: High grade + Unifocal <1.5 cm
- 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.
Show all 15Show fewer
- Eligible to receive enfortumab vedotin plus pembrolizumab (EV-P) in the opinion of the investigators.
- Written informed consent obtained from the subject and the subject agrees to comply with all the study-related procedures.
- Subjects must not have more than one active malignancy at the time of enrollment.
- 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 investigational regimen or primary endpoint (as determined by the treating physician) are eligible for this trial.
- Subjects of childbearing potential (SOCBP) must be using an adequate method of contraception 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-menopausal. Post-menopause is defined as:
- Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or
- 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.
- Subjects with partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 4 months following the last dose of EV-P.
Who cannot join
- Histology that contains any component of neuroendocrine carcinoma.
- Any known contraindications to enfortumab vedotin plus pembrolizumab.
- Subjects who are confirmed to be pregnant or breastfeeding.
- History of any other disease, metabolic dysfunction, clinical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician.
- Administration of a vaccine containing live virus within 30 days prior to the first dose of trial treatment. Note: Most flu vaccines are killed viruses, with the exception of the intra-nasal vainer (Flu-Mist) which is an attenuated live virus and therefore prohibited for 30 days prior to first dose.
- Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.
About this study
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.
Read more
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.
- Conditions
- Urothelial Carcinoma (UC)
- Being tested
- enfortumab vedotin and pembrolizumab (EV/P)
- Keywords
- bladder cancer, cystectomy, enfortumab vedotin, muscle invasive bladder cancer, pembrolizumab, urothelial carcinoma, upper tract urothelial carcinoma
- Medical subject headings
- Carcinoma, Transitional Cell, Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
enfortumab vedotin and pembrolizumab (EV/P)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A (neoadjuvant EV-P + response-adapted management) | Experimental | 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. Receives: Drug: enfortumab vedotin and pembrolizumab (EV/P) |
| Cohort B (neoadjuvant EV-P + surgery + adjuvant EV-P) | Experimental | Not described Receives: Drug: enfortumab vedotin and pembrolizumab (EV/P) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 8 weeks following completion of neoadjuvant therapy
Secondary outcomes (11)
Event-free survival
Determine the event-free survival of patients in Cohort A at 1 year from the start of EV-P
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: At completion of first 4 cycles of EV-P (each cycle of EV-P is 21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2026
- Study startDec 2026 (estimated)
- Primary completionFeb 2029 (estimated)
- Study completionOct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urothelial Carcinoma (UC)Studies of the same condition, open and under way.
- More trials run by University of FloridaThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 39 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Daniel Araujo, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07643519
- Sponsor's protocol ID
- UF-GU-014
- Status last verified
- Sep 2026
- First submitted
- 3 Jun 2026
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Enfortumab Vedotin Plus Pembrolizumab in Muscle-Invasive Bladder Cancer and Upper Tract Urothelial Carcinoma
- ClinicalTrials.gov ID
- NCT07643519
- Acronym / sponsor ID
- UF-GU-014
- Conditions
- Urothelial Carcinoma (UC)
- Keywords
- bladder cancer, cystectomy, enfortumab vedotin, muscle invasive bladder cancer, pembrolizumab, urothelial carcinoma, upper tract urothelial carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 39 participants (estimated)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- Dec 2026 (estimated)
- Primary completion
- Feb 2029 (estimated)
- Study completion
- Oct 2030 (estimated)
- First posted
- 11 Jun 2026 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A (neoadjuvant EV-P + response-adapted management) | Experimental | Drug: enfortumab vedotin and pembrolizumab (EV/P)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. |
| Cohort B (neoadjuvant EV-P + surgery + adjuvant EV-P) | Experimental | Drug: enfortumab vedotin and pembrolizumab (EV/P) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Adults ≥ 18 years of age.
- ECOG Performance Status of 0-2
- For Cohort A, a clinical or pathological diagnosis consistent with muscle-invasive urothelial carcinoma of the bladder (locoregional), with a clinical staging of T2 or higher, N0 to N2, and M0.
- 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-intermediate: High grade + Unifocal <1.5 cm
Key exclusion criteria (6 listed)
- Histology that contains any component of neuroendocrine carcinoma.
- Any known contraindications to enfortumab vedotin plus pembrolizumab.
- Subjects who are confirmed to be pregnant or breastfeeding.
- History of any other disease, metabolic dysfunction, clinical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician.
- Administration of a vaccine containing live virus within 30 days prior to the first dose of trial treatment. Note: Most flu vaccines are killed viruses, with the exception of the intra-nasal vainer (Flu-Mist) which is an attenuated live virus and therefore prohibited for 30 days prior to first dose.
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 |
|---|---|---|
| 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. | Drug | Cohort A (neoadjuvant EV-P + response-adapted management), Cohort B (neoadjuvant EV-P + surgery + adjuvant EV-P) |
Primary outcome
Clinical complete response rate
Time frame: 3 weeks following completion of neoadjuvant therapy
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.
Pathologic complete response rate
Time frame: 8 weeks following completion of neoadjuvant therapy
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.
11 secondary outcomes
Event-free survival
Time frame: 1 year from the start of EV-P
Event-free survival
Time frame: 2 years from the start of EV-P
Overall survival
Time frame: 1 year from the start of EV-P
Overall survival
Time frame: 2 years from the start of EV-P
Bladder-intact survival
Time frame: 1 year from the start of EV-P
Bladder-intact survival
Time frame: 2 years from the start of EV-P
Pathological complete response
Time frame: After completion of first 4 cycles of EV-P (each cycle of EV-P is 21 days)
Pathologic downstaging
Time frame: At completion of first 4 cycles of EV-P (each cycle of EV-P is 21 days)
Event-free survival
Time frame: 2 years from the start of EV-P
Overall survival
Time frame: 2 years from the start of EV-P
Pathologic downstaging
Time frame: At completion of first 4 cycles of EV-P (each cycle of EV-P is 21 days)
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 14 Sep 2026.
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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.
Daniel Araujo, MD principal investigator
University of Florida
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing enfortumab vedotin and pembrolizumab (EV/P) in people with Urothelial Carcinoma (UC), run by University of Florida.
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 15 inclusion and 6 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: opening soon, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical complete response rate (time frame: 3 weeks following completion of neoadjuvant therapy). 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 14 Sep 2026.