Muscle-invasive Bladder Urothelial CarcinomaPhase 2PRESERVENCT07822373
A Phase 2 Study Evaluating Bladder Preservation With Enfortumab Vedotin Plus Pembrolizumab in Patients With Muscle-Invasive Urothelial Cancer
A Phase 2 study testing Enfortumab vedotin and Pembrolizumab in people with Muscle-invasive Bladder Urothelial Carcinoma, run by University of Utah at 1 site in United States.
Trial summary
The purpose of this study is to evaluate whether Enfortumab Vedotin in combination with Pembrolizumab can achieve a clinical response that preserves the bladder and avoids the need for cystectomy or radiation therapy in patients with urothelial cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Muscle-invasive Bladder Urothelial Carcinoma
- What is being tested?
- Enfortumab vedotin and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2026to Nov 2035
- 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
- Participant aged ≥ 18 years.
- Disease criteria:
- Histologically confirmed muscle-invasive urothelial carcinoma (T2-T3N0M0) without small cell variant histology of bladder. Other variant histologies are allowed if urothelial histology is present.
- No evidence of local or distant metastasis on CT scans.
- Urothelial carcinomas not originating from the bladder (eg, upper tract [ureters, renal pelvis], urethra) are not eligible.
- Eligible to receive enfortumab vedotin and pembrolizumab.
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- ECOG Performance Status ≤ 2.
- Adequate organ function as defined as:
- Hematologic:
- Absolute neutrophil count ≥ 1500/mm3
- Platelet count ≥ 100,000/mm3
- Hemoglobin ≥ 10 g/dL
- Hepatic:
- Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN), ≤3× ULN for subjects with suspected Gilbert's syndrome with direct bilirubin ≤ ULN.
- ----AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN
- Renal:
- Estimated creatinine clearance ≥ 30 mL/min by Cockcroft-Gault formula (or measured by 24-hour urine collection).
- Participants must adhere to the following sex and contraceptive/barrier requirements:
- If participant is of childbearing potential, they must have a negative pregnancy test.
- For participants of non-childbearing potential: The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause or having undergone surgical sterilization (bilateral oophorectomy or hysterectomy). The following age-specific requirements apply:
- < 50 years of age:
- Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and
- Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution
- --≥ 50 years of age:
- Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or
- Had radiation-induced menopause with last menses >1 year ago; or
- Had chemotherapy-induced menopause with last menses >1 year ago
- Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution
- Participants of childbearing potential and participants with a sexual partner of childbearing potential must agree to use a highly effective method of contraception and lactation requirements as described in Sections 5.4.2 and 5.4.3.
- Clinically significant adverse effects from any prior oncologic treatment (e.g. prior surgery, radiotherapy, or other antineoplastic therapy) must have resolved or have been determined to be clinically stable per the Investigator.
- Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
- Participant has been counseled on standard of care treatment options available to them and has expressed they are interested in pursuing bladder preservation without cystectomy or radiation.
- The discussion regarding the choice of standard therapy offered, if available, and patient's choice to decline standard therapy should be documented clearly in the research chart.
Who cannot join
- Prior systemic therapy for urothelial cancer.
- Receiving other systemic investigational agents for urothelial cancer.
- Hemoglobin A1c > 8% or 7-8% with associated diabetes symptoms.
- Autoimmune disease requiring systemic steroids or immunosuppressive agents in the last 2 years.
- Neuropathy Grade ≥2.
- Prior radiotherapy for urothelial cancer.
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- Major surgery within 4 weeks prior to starting study therapy or participant has not fully recovered from major surgery per clinical investigator.
- The diagnosis of another malignancy which, in the opinion of the Investigator, is likely to negatively impact study objectives or the participant's safety or ability to participate in the study.
- Known metastatic disease.
- Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
- Cardiovascular disorders:
- Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious cardiac arrhythmias per clinical investigator.
- Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other significant ischemic events per clinical investigator, within 3 months before the first dose. Subjects with pulmonary embolism or deep vein thrombosis if adequately managed can be enrolled.
- Any other condition that would, in the Investigator's judgment, contraindicate the participant's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, social/ psychological issues, etc.)
- Active infection expected to interfere with study treatment in the opinion of the investigator.
- Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment.
- --Note: Participants on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial.
- Hepatitis B (known positive HBV surface antigen (HBsAg) result), or hepatitis C.
- Note: Participants with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Participants positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- Medical, psychiatric, cognitive, or other conditions that may compromise the participant's ability to understand the participant information, give informed consent, comply with the study protocol or complete the study.
- Known prior severe hypersensitivity to investigational product or any component in its formulations (CTCAE v6.0 Grade ≥ 3).
- Participants taking prohibited medications as described in Section 6.8.2.
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
Huntsman Cancer Institute at University of Utah
Salt Lake City, Utah, 84112
Kristen Jewkes, 801-585-1753, Kristen.Jewkes@hci.utah.edu
Umang Swami, MD, 801-585-0255, Umang.Swami@hci.utah.edu
About this study
Official title: PRESERVE: A Phase 2 Study Evaluating Bladder Preservation With Enfortumab Vedotin Plus Pembrolizumab in Patients With Muscle-Invasive Urothelial Cancer
The purpose of this study is to evaluate whether Enfortumab Vedotin in combination with Pembrolizumab can achieve a clinical response that preserves the bladder and avoids the need for cystectomy or radiation therapy in patients with urothelial cancer.
- Being tested
- Enfortumab vedotin, Pembrolizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enfortumab vedotinDrug
Enfortumab vedotin 1.25 mg/kg, IV on days 1 and 8 on a 21day cycle for 9 cycles
PembrolizumabDrug
Subjects will receive one year of treatment with pembrolizumab IV or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) SC. Treatment will be administered per institutional standards every 3 weeks or 6 weeks, at the physician's discretion.
| Study group | Role | What they receive |
|---|---|---|
| Treatment: All Patients | Experimental | All patients will be treated with enfortumab vedotin in combination with pembrolizumab. Receives: Drug: Enfortumab vedotin; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
cT0 or cTa low-grade disease as assessed by cystoscopy and bladder biopsy, including all visually abnormal sites in addition to reTURBT or biopsy of the known site of MIBC before neo- adjuvant therapy
To assess the proportion of patients who have achieved a clinical complete response and have maintained bladder preservation without undergoing definitive treatment of cystectomy or radiation after 4 cycles of study treatment.
Measured: 6 years
Negative tumor-informed ctDNA
To assess the proportion of patients who have achieved a clinical complete response and have maintained bladder preservation without undergoing definitive treatment of cystectomy or radiation after 4 cycles of study treatment.
Measured: 6 years
The absence of malignant cells on urine cytology
To assess the proportion of patients who have achieved a clinical complete response and have maintained bladder preservation without undergoing definitive treatment of cystectomy or radiation after 4 cycles of study treatment.
Measured: 6 years
No definitive evidence of new local or metastatic disease at cross-sectional imaging per investigator judgement
To assess the proportion of patients who have achieved a clinical complete response and have maintained bladder preservation without undergoing definitive treatment of cystectomy or radiation after 4 cycles of study treatment.
Measured: 6 years
Secondary outcomes (13)
The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type.
To assess the safety and tolerability of enfortumab vedotin in combination with pembrolizumab in the study population.
Measured: 6 years
The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by severity (as defined by the NIH CTCAE, version 6.0).
To assess the safety and tolerability of enfortumab vedotin in combination with pembrolizumab in the study population.
Measured: 6 years
The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by seriousness.
To assess the safety and tolerability of enfortumab vedotin in combination with pembrolizumab in the study population.
Measured: 6 years
The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by duration.
To assess the safety and tolerability of enfortumab vedotin in combination with pembrolizumab in the study population.
Measured: 6 years
The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by their relationship to the study treatment.
To assess the safety and tolerability of enfortumab vedotin in combination with pembrolizumab in the study population.
Measured: 6 years
Residual or recurrent MIBC, as assessed by biopsy
To assess bladder intact event-free survival (EFS), defined as the time from treatment initiation to the first occurrence of any of the following events:
- residual or recurrent MIBC, as assessed by biopsy;
- local or distant disease (N1, N2, N3 or M1) disease as confirmed histologically or as assessed by imaging if biopsy is not feasible due to safety concerns;
- cystectomy or radiation to bladder;
- death from any cause
Measured: 6 years
Local or distant disease (N1, N2, N3 or M1) disease as confirmed histologically or as assessed by imaging if biopsy is not feasible due to safety concerns.
To assess bladder intact event-free survival (EFS), defined as the time from treatment initiation to the first occurrence of any of the following events:
- residual or recurrent MIBC, as assessed by biopsy;
- local or distant disease (N1, N2, N3 or M1) disease as confirmed histologically or as assessed by imaging if biopsy is not feasible due to safety concerns;
- cystectomy or radiation to bladder;
- death from any cause
Measured: 6 years
Cystectomy or radiation to bladder
To assess bladder intact event-free survival (EFS), defined as the time from treatment initiation to the first occurrence of any of the following events:
- residual or recurrent MIBC, as assessed by biopsy;
- local or distant disease (N1, N2, N3 or M1) disease as confirmed histologically or as assessed by imaging if biopsy is not feasible due to safety concerns;
- cystectomy or radiation to bladder;
- death from any cause
Measured: 6 years
Death from any cause
To assess bladder intact event-free survival (EFS), defined as the time from treatment initiation to the first occurrence of any of the following events:
- residual or recurrent MIBC, as assessed by biopsy;
- local or distant disease (N1, N2, N3 or M1) disease as confirmed histologically or as assessed by imaging if biopsy is not feasible due to safety concerns;
- cystectomy or radiation to bladder;
- death from any cause
Measured: 6 years
The time to NMIBC defined as the time from treatment initiation to the first occurrence of NMIBC (cTa, cT1, or carcinoma in situ) as assessed by biopsy.
To assess time to non-muscle invasive bladder cancer (NMIBC) defined as the time from treatment initiation to the first occurrence of NMIBC (cTa, cT1, or carcinoma in situ) as assessed by biopsy.
Measured: 6 years
Local or distant disease (N1, N2, N3 or M1) disease as confirmed histologically or as assessed by imaging if biopsy is not feasible due to safety concerns.
To assess distant disease-free survival (DDFS) defined as the time from treatment initiation to the first occurrence of any of the following events:
- local or distant disease (N1, N2, N3 or M1) disease as confirmed histologically or as assessed by imaging if biopsy is not feasible due to safety concerns;
- death from any cause
Measured: 6 years
Death from any cause
To assess distant disease-free survival (DDFS) defined as the time from treatment initiation to the first occurrence of any of the following events:
- local or distant disease (N1, N2, N3 or M1) disease as confirmed histologically or as assessed by imaging if biopsy is not feasible due to safety concerns;
- death from any cause
Measured: 6 years
Overall survival (OS) as defined as the time from initiation of treatment until death from any cause.
To assess overall survival in this study population.
Measured: 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2026
- Study startNov 2026 (estimated)
- Primary completionNov 2034 (estimated)
- Study completionNov 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Muscle-invasive Bladder Urothelial CarcinomaStudies of the same condition, open and under way.
- 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
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07822373
- Sponsor's protocol ID
- HCI205161
- Acronym
- PRESERVE
- Status last verified
- Sep 2026
- First submitted
- 10 Sep 2026
- Last updated
- 16 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 16 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PRESERVE: A Phase 2 Study Evaluating Bladder Preservation With Enfortumab Vedotin Plus Pembrolizumab in Patients With Muscle-Invasive Urothelial Cancer
- ClinicalTrials.gov ID
- NCT07822373
- Acronym / sponsor ID
- PRESERVE / HCI205161
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- Nov 2026 (estimated)
- Primary completion
- Nov 2034 (estimated)
- Study completion
- Nov 2035 (estimated)
- First posted
- 16 Sep 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.
The purpose of this study is to evaluate whether Enfortumab Vedotin in combination with Pembrolizumab can achieve a clinical response that preserves the bladder and avoids the need for cystectomy or radiation therapy in patients with urothelial cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment: All Patients | Experimental | Drug: Enfortumab vedotin, Drug: PembrolizumabAll patients will be treated with enfortumab vedotin in combination with pembrolizumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (33 listed)
- Participant aged ≥ 18 years.
- Disease criteria:
- Eligible to receive enfortumab vedotin and pembrolizumab.
- ECOG Performance Status ≤ 2.
- Adequate organ function as defined as:
Key exclusion criteria (22 listed)
- Prior systemic therapy for urothelial cancer.
- Receiving other systemic investigational agents for urothelial cancer.
- Hemoglobin A1c > 8% or 7-8% with associated diabetes symptoms.
- Autoimmune disease requiring systemic steroids or immunosuppressive agents in the last 2 years.
- Neuropathy Grade ≥2.
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 vedotinEnfortumab vedotin 1.25 mg/kg, IV on days 1 and 8 on a 21day cycle for 9 cycles | Drug | Treatment: All Patients |
| PembrolizumabSubjects will receive one year of treatment with pembrolizumab IV or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) SC. Treatment will be administered per institutional standards every 3 weeks or 6 weeks, at the physician's discretion. | Drug | Treatment: All Patients |
Primary outcome
cT0 or cTa low-grade disease as assessed by cystoscopy and bladder biopsy, including all visually abnormal sites in addition to reTURBT or biopsy of the known site of MIBC before neo- adjuvant therapy
Time frame: 6 years
To assess the proportion of patients who have achieved a clinical complete response and have maintained bladder preservation without undergoing definitive treatment of cystectomy or radiation after 4 cycles of study treatment.
Negative tumor-informed ctDNA
Time frame: 6 years
To assess the proportion of patients who have achieved a clinical complete response and have maintained bladder preservation without undergoing definitive treatment of cystectomy or radiation after 4 cycles of study treatment.
The absence of malignant cells on urine cytology
Time frame: 6 years
To assess the proportion of patients who have achieved a clinical complete response and have maintained bladder preservation without undergoing definitive treatment of cystectomy or radiation after 4 cycles of study treatment.
No definitive evidence of new local or metastatic disease at cross-sectional imaging per investigator judgement
Time frame: 6 years
To assess the proportion of patients who have achieved a clinical complete response and have maintained bladder preservation without undergoing definitive treatment of cystectomy or radiation after 4 cycles of study treatment.
13 secondary outcomes
The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type.
Time frame: 6 years
The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by severity (as defined by the NIH CTCAE, version 6.0).
Time frame: 6 years
The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by seriousness.
Time frame: 6 years
The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by duration.
Time frame: 6 years
The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by their relationship to the study treatment.
Time frame: 6 years
Residual or recurrent MIBC, as assessed by biopsy
Time frame: 6 years
Local or distant disease (N1, N2, N3 or M1) disease as confirmed histologically or as assessed by imaging if biopsy is not feasible due to safety concerns.
Time frame: 6 years
Cystectomy or radiation to bladder
Time frame: 6 years
Death from any cause
Time frame: 6 years
The time to NMIBC defined as the time from treatment initiation to the first occurrence of NMIBC (cTa, cT1, or carcinoma in situ) as assessed by biopsy.
Time frame: 6 years
Local or distant disease (N1, N2, N3 or M1) disease as confirmed histologically or as assessed by imaging if biopsy is not feasible due to safety concerns.
Time frame: 6 years
Death from any cause
Time frame: 6 years
Overall survival (OS) as defined as the time from initiation of treatment until death from any cause.
Time frame: 6 years
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 16 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.
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 Enfortumab vedotin and Pembrolizumab in people with Muscle-invasive Bladder Urothelial Carcinoma, run by University of Utah 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 33 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: opening soon, as of the sponsor's last update on 16 Sep 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 Kristen Jewkes (801-585-1753, Kristen.Jewkes@hci.utah.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
cT0 or cTa low-grade disease as assessed by cystoscopy and bladder biopsy, including all visually abnormal sites in addition to reTURBT or biopsy of the known site of MIBC before neo- adjuvant therapy (time frame: 6 years). The study lists 4 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 16 Sep 2026; AzTrials last refreshed its copy on 28 Oct 2026.