Adenocarcinoma of the BladderPhase 2NCT06041503
Enfortumab Vedotin With or Without Pembrolizumab in Rare Genitourinary Tumors (E-VIRTUE)
A Phase 2 study testing Pembrolizumab and Enfortumab vedotin in people with Adenocarcinoma of the Bladder and Squamous Cell Carcinoma of the Bladder, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Many cancers of the testicles and urinary tract are rare diseases; these are diseases that affect less than 200,000 people in the United States. It can be hard to study treatments for these diseases. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Adenocarcinoma of the Bladder, Squamous Cell Carcinoma of the Bladder, Testicular Germ Cell Tumors
- What is being tested?
- Pembrolizumab and Enfortumab vedotin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jan 2026to 1 Oct 2028
- 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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must have histologically confirmed locally advanced or metastatic pure adenocarcinoma of the urinary tract, pure squamous cell carcinoma of the urinary tract, or treatment-refractory testicular germ cell tumors. Note: For the purposes of enrollment, the urinary tract is defined as the renal pelvis, ureter, bladder, and urethra.
- Participants must have measurable disease, per RECIST 1.1.
- Participants must have locally advanced or metastatic disease defined as new or progressive lesions on cross sectional imaging.
- Participants in Cohorts A1, B1, and C1 must have received prior anti-PD-1/PD-L1 therapy in any setting.
- Participants in Cohorts A2, B2, and C2 must be immune checkpoint inhibitor naive.
- Participants may be systemic treatment naive except for participants with testicular germ cell tumors, who must have received and be refractory to all standard options of curative-intent treatment.
Show all 23Show fewer
- Age >= 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status <= 1 (Karnofsky >= 70%)
- Participants must have adequate organ and marrow function as defined below:
- Hemoglobin (Hgb) >= 9g/dL
- Absolute neutrophil count (ANC) >= 1,500/mcL
- Platelets >= 100,000/mcL
- Total bilirubin <= 1.5 x upper limit of normal (ULN) (<= 3 x ULN in participants with known/suspected Gilbert's disease)
- Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) <= 2.5 x institutional ULN
- Creatinine clearance (CrCl) >= 30 mL/min/1.73m^2 as estimated per institution standards.
- Pre-study treatment tissue availability (sufficient tissue for 25 unstained slides) is mandatory for enrollment. If tissue is determined to be insufficient/unsuitable, a fresh biopsy prior to study therapy will be required.
- Human immunodeficiency virus (HIV) positive participants are eligible if on stable dose of highly active antiretroviral therapy (HAART) for at least 3 months, CD4 counts are > 200 cells/mm^3 and viral load (VL) is undetectable.
- Hepatitis B virus (HBV) positive participants are eligible if they have been treated or are on an appropriate course of antivirals at study entry and with planned monitoring and management according to appropriate guidance. For previously treated participants or those with prior infection that has been cleared, prophylaxis is permitted, and hepatology consultation recommended.
- Hepatitis C virus (HCV) positive participants are eligible if participants are on active HCV therapy at study entry and on a stable dose of antivirals without documented clinically significant impaired liver function test or hematologic abnormalities and with planned monitoring and management according to appropriate labeling, or if they are post-treatment for HCV. Participants that are positive for hepatitis C must have a negative polymerase chain reaction (PCR).
- Women of child-bearing potential (WOCBP) must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence prior to study entry, for the duration of study participation, and for at least 4 months after the last dose of study drug(s).
- Men able to father children must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) for the duration of the study treatment and up to 4 months after the last dose of the study drug(s). We also will recommend men with female partners of childbearing potential to ask female partners to be on an effective birth control (hormonal, intrauterine device (IUD), surgical sterilization).
- Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 4 months after the last dose of the pembrolizumab and 3 weeks after the last dose of EV.
- Participants must be able to understand and willing to sign a written informed consent document.
Who cannot join
- Participants with prior investigational drug, chemotherapy, immunotherapy, or any prior radiotherapy (except for palliative bone directed therapy) within the past 2 weeks prior to the first study drug administration. Note: FDA-approved hormonal therapy for the treatment or prevention of other malignancies (e.g., breast cancer, prostate cancer) are allowed to be continued where in the opinion of the investigator stopping such therapies may increase the risk of disease progression. Potential drug-drug interactions with the hormonal agent will be assessed by the investigator prior to enrollment.
- Participants with prior treatment with EV or other MMAE-based ADCs.
- Participants with preexisting sensory or motor neuropathy Grade >= 2.
- History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to EV and/or pembrolizumab.
- Symptomatic or untreated central nervous system (CNS) metastases. Note: Participants with previously treated brain or CNS metastases are eligible if the participants have recovered from any acute effects of radiotherapy and not requiring steroids, and any whole brain radiation therapy or any stereotactic radiosurgery was completed at least 2 weeks prior to initiation of study therapy.
- Participants will be excluded if they have an active autoimmune disease that might deteriorate when receiving pembrolizumab except for:
Show all 16Show fewer
- Diabetes type I, eczema, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment.
- Participants requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses <= 10 mg of prednisone or equivalent per day.
- Administration of steroids for other conditions through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation).
- Participants on systemic intravenous or oral corticosteroid therapy with the exception of physiologic doses of corticosteroids (<= the equivalent of prednisone 10 mg/day) or other immunosuppressive agents such as azathioprine or cyclosporin A are excluded on the basis of potential immune suppression. For these participants these excluded treatments must be discontinued at least 1 week prior to treatment initiation for recent short course use (<= 14 days) or discontinued at least 4 weeks prior to treatment initiation for long term use (> 14 days). In addition, the use of corticosteroids as premedication for contrast-enhanced studies is allowed prior to treatment initiation and on study.
- History of uncontrolled diabetes mellitus within 3 months before the first dose of EV. Uncontrolled diabetes is defined as hemoglobin A1C (HbA1c) >= 8% or HbA1c between 7 and < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
- Active keratitis or corneal ulcerations.
- Participants who have received or will receive a live vaccine within 30 days prior to the first administration of study intervention. Seasonal flu vaccines that do not contain a live virus are permitted. Locally approved COVID-19 vaccines are permitted.
- Pregnant women as evaluated by a positive serum or urine beta-human chorionic gonadotropin (Beta-hCG) test at screening.
- Participants with severe uncontrolled intercurrent illness that would limit compliance with study requirements, as evaluated by history, physical exam, and chemistry panel.
- Participants with severe uncontrolled intercurrent illness that would limit compliance with study requirements, as evaluated by history, physical exam, and chemistry panel. Participants with a prior (within 2 years of study therapy initiation) 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 will be permitted to join the study.
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
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
National Cancer Institute Referral Office, 888-624-1937
About this study
Official title: A Phase II Multicenter Study of Enfortumab Vedotin With or Without Pembrolizumab in Rare Genitourinary Tumors (E-VIRTUE)
Background:
Many cancers of the testicles and urinary tract are rare diseases; these are diseases that affect less than 200,000 people in the United States. It can be hard to study treatments for these diseases. One combination of drugs-enfortumab vedotin (EV) and pembrolizumab-has already been approved to treat some urinary cancers. Researchers want to see if they can help people with other types of testicle and urinary cancers.
Read more
Objective:
To test EV, with or without pembrolizumab, in patients with rarer cancers of the testicles or urinary tract.
Eligibility:
People aged 18 and older with rarer cancers of the testicles or urinary tract.
Design:
Participants will be screened. They will have a physical exam with blood and urine tests. Their ability to perform normal daily activities will be tested. They will have exams of their skin and eyes. They will have imaging scans. A biopsy may be needed: A sample of tissue will be removed from the tumor.
The study drugs are both given through a tube attached to a needle inserted into a vein in the arm. Some participants will receive treatments 3 times during 28-week cycles; others will receive treatments 2 times during 21-day cycles.
All participants may continue to receive treatments for up to 5 years. Imaging scans and other tests will be repeated.
Participants who stop taking the drugs will have follow-up visits every 3 to 4 weeks until the disease gets worse. They will have imaging scans and blood tests.
After that, follow-up visits will continue by phone every 3 months for up to 5 years after study therapy is finished.
Read the detailed description
Background:
- Rare genitourinary (GU) tumors are tumors of aberrant histology occurring in the GU tract including kidney, bladder, ureters, testes, and penis. Due to their rarity, they are not systematically captured by currently available registries, treatment protocols or tissue banks.
- Large randomized clinical trials are logistically difficult in these small patient populations. Therefore, treatment information is obtained from case reports, retrospective studies, and small clinical trials, and is frequently extrapolated from trials on similar tumor types.
- Pembrolizumab is a potent and highly selective humanized monoclonal antibody that targets immune checkpoint programmed cell death protein 1 (PD-1) receptor.
- Nectin-4 is a type 1 transmembrane protein and member of a family of related immunoglobulinlike adhesion molecules implicated in cell-cell adhesion.
- Nectin-4 is highly expressed in cancer cells, particularly in urothelial carcinomas (UCs).
- Enfortumab vedotin (EV) is an antibody-drug conjugate consisting of a human monoclonal antibody to nectin-4 and monomethyl auristatin E (MMAE), a microtubule disrupting cytotoxic agent. EV has demonstrated a survival benefit in the setting of metastatic urothelial carcinoma, which has almost universally high nectin-4 expression.
- There is data in UC and bladder cancer variants showing co-existence of nectin-4 expression and programmed cell death 1 ligand 1 (PD-L1) expression and mismatch repair deficiency.
- There is currently very limited data on the level of nectin-4 expression in rare GU tumors and no evidence for the activity of EV in these tumors.
Objective:
-To assess the objective response rate (ORR) per RECIST v 1.1 in participants with rare genitourinary (GU) tumors treated with enfortumab vedotin (EV) with or without pembrolizumab.
Eligibility:
- Age >= 18 years
- Histologically confirmed diagnosis of locally advanced or metastatic pure adenocarcinoma of the urinary tract, pure squamous cell carcinoma of the urinary tract, or treatment-refractory testicular germ cell tumors.
- Participants may have received any number of prior anti-cancer treatments or be treatment na(SqrRoot) ve (with the exception of participants with testicular germ cell tumors, who must have exhausted all standard curative-intent options).
Design:
- This multisite study is a Phase II, open label, multicohort, nonrandomized study with two arms.
- Participants with:
- Adenocarcinoma of the urinary tract will be enrolled in Cohort A (Cohort A1: prior anti-1/PD-L1 therapy; Cohort A2: no prior anti-PD-1/PD-L1 therapy).
- Squamous cell carcinoma of the urinary tract will be enrolled in Cohort B (Cohort B1: prior anti-PD-1/PD-L1 therapy; Cohort B2: no prior anti-PD-1/PD-L1 therapy).
- Testicular germ cell tumors will be enrolled in Cohort C (Cohort C1: prior anti-PD-1/PDL1 therapy; Cohort C2: no prior anti-PD-1/PD-L1 therapy).
- All participants will receive EV.
- Participants without prior immune checkpoint inhibitor (ICI) exposure will be eligible to receive concurrent pembrolizumab.
- Arm 1: EV monotherapy will be given in 28-day cycles for a maximum of 5 years, or until disease progression or intolerable side effects. EV will be administered I.V. at 1.25 mg/kg on days 1, 8, and 15 of each cycle.
- Arm 2: EV and pembrolizumab will be given in 21-day cycles. EV will be administered I.V. at 1.25 mg/kg on days 1 and 8 of each cycle. Pembrolizumab will be administered I.V. at 200 mg on day 1.
- EV and pembrolizumab will be given for 35 cycles, or until a confirmed complete response, disease progression or intolerable side effects.
- After the 35th cycle, EV may be continued to be given for a maximum of 5 years, or until disease progression or intolerable side effects.
- Participants who have completed 35 cycles of pembrolizumab or stopped pembrolizumab for confirmed complete response may be eligible for up to additional 17 cycles of pembrolizumab if there is investigator-determined progressive disease by RECIST 1.1 after initial treatment.
- The accrual ceiling will be set at 68 participants to allow for inevaluable participants.
- Conditions
- Adenocarcinoma of the Bladder, Squamous Cell Carcinoma of the Bladder, Testicular Germ Cell Tumors
- Being tested
- Pembrolizumab, Enfortumab vedotin
- Keywords
- Immunotherapy, nectin 4, rare genitourinary cancers, programmed cell death 1 ligand 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Pembrolizumab is administered IV at 200 mg on day 1 of each 21-day cycle.
Enfortumab vedotinDrug
EV is administered IV at 1.25 mg/kg on days 1, 8, and 15 of each 28-day cycle (Arm 1) and on days 1 and 8 of each 21-day cycle (Arm 2).
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Treatment with enfortumab vedotin Receives: Drug: Enfortumab vedotin |
| Arm 2 | Experimental | Treatment with enfortumab vedotin and pembrolizumab Receives: Drug: Pembrolizumab; Drug: Enfortumab vedotin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR)
Percentage of participants by best overall response (e.g., CR, PR, SD, PD) to therapy
Measured: At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD
Secondary outcomes (6)
Second Objective response rate (ORR2) and second progression-free survival (PFS2) after second course of pembrolizumab
Percentage of participants with the best overall response of CR or PR to therapy and duration of time from start of treatment to time of progression or death, whichever occurs first.
Measured: At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD
Duration of response (DoR)
Time from start of treatment to disease progression or death in participants who achieve CR or PR
Measured: At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD
Overall survival (OS)
Time from the start of treatment that participants are still alive.
Measured: Day 1 of each cycle, at EoT, at the Safety visits, and every 90 days for up to a total of 5 years after the end of therapy.
Progression-free survival (PFS)
Duration of time from start of treatment to time of progression or death, whichever occurs first
Measured: At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD
Clinical benefit rate (CBR)
Percentage of participant who have achieved CR, PR, and SD while on treatment.
Measured: At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD
Safety of EV with or without pembrolizumab
Adverse events (AEs) will be reported by type and grade of toxicity
Measured: From first dose through 30 days after last treatment with EV and 90 days after last treatment with pembrolizumab
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2023
- Study start20 Jan 2026
- Primary completion1 Oct 2027 (estimated)
- Study completion1 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adenocarcinoma of the BladderStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Andrea B Apolo, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06041503
- Sponsor's protocol ID
- 10001533
- Other IDs
- 001533-C
- Status last verified
- 11 Aug 2026
- First submitted
- 15 Sep 2023
- Last updated
- 13 Aug 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All collected IPD will be shared
Publications
Chandran EBA, Atiq S, Simon N, Girardi D, Ley L, Cordes L, Patel R, Wang TF, Kydd AR, Redd B, Boudjadi S, Stukes I, Banday R, Smith E, Akbulut D, Niglio S, Gurram S, Steinberg S, Apolo AB. E-VIRTUE: a study of enfortumab vedotin with or without pembrolizumab in rare genitourinary tumors-design and rationale. Future Oncol. 2025 Jun;21(13):1625-1630. doi: 10.1080/14796694.2025.2497719. Epub 2025 May 27.
PubMed 40421891
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Multicenter Study of Enfortumab Vedotin With or Without Pembrolizumab in Rare Genitourinary Tumors (E-VIRTUE)
- ClinicalTrials.gov ID
- NCT06041503
- Acronym / sponsor ID
- 10001533
- Conditions
- Adenocarcinoma of the Bladder, Squamous Cell Carcinoma of the Bladder, Testicular Germ Cell Tumors
- Keywords
- Immunotherapy, nectin 4, rare genitourinary cancers, programmed cell death 1 ligand 1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 20 Jan 2026 (actual)
- Primary completion
- 1 Oct 2027 (estimated)
- Study completion
- 1 Oct 2028 (estimated)
- First posted
- 18 Sep 2023 (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.
Background:
Many cancers of the testicles and urinary tract are rare diseases; these are diseases that affect less than 200,000 people in the United States. It can be hard to study treatments for these diseases. One combination of drugs-enfortumab vedotin (EV) and pembrolizumab-has already been approved to treat some urinary cancers. Researchers want to see if they can help people with other types of testicle and urinary cancers.
Objective:
To test EV, with or without pembrolizumab, in patients with rarer cancers of the testicles or urinary tract.
Eligibility:
People aged 18 and older with rarer cancers of the testicles or urinary tract.
Design:
Participants will be screened. They will have a physical exam with blood and urine tests. Their ability to perform normal daily activities will be tested. They will have exams of their skin and eyes. They will have imaging scans. A biopsy may be needed: A sample of tissue will be removed from the tumor.
The study drugs are both given through a tube attached to a needle inserted into a vein in the arm. Some participants will receive treatments 3 times during 28-week cycles; others will receive treatments 2 times during 21-day cycles.
All participants may continue to receive treatments for up to 5 years. Imaging scans and other tests will be repeated.
Participants who stop taking the drugs will have follow-up visits every 3 to 4 weeks until the disease gets worse. They will have imaging scans and blood tests.
After that, follow-up visits will continue by phone every 3 months for up to 5 years after study therapy is finished.
Detailed description
Background:
- Rare genitourinary (GU) tumors are tumors of aberrant histology occurring in the GU tract including kidney, bladder, ureters, testes, and penis. Due to their rarity, they are not systematically captured by currently available registries, treatment protocols or tissue banks.
- Large randomized clinical trials are logistically difficult in these small patient populations. Therefore, treatment information is obtained from case reports, retrospective studies, and small clinical trials, and is frequently extrapolated from trials on similar tumor types.
- Pembrolizumab is a potent and highly selective humanized monoclonal antibody that targets immune checkpoint programmed cell death protein 1 (PD-1) receptor.
- Nectin-4 is a type 1 transmembrane protein and member of a family of related immunoglobulinlike adhesion molecules implicated in cell-cell adhesion.
- Nectin-4 is highly expressed in cancer cells, particularly in urothelial carcinomas (UCs).
- Enfortumab vedotin (EV) is an antibody-drug conjugate consisting of a human monoclonal antibody to nectin-4 and monomethyl auristatin E (MMAE), a microtubule disrupting cytotoxic agent. EV has demonstrated a survival benefit in the setting of metastatic urothelial carcinoma, which has almost universally high nectin-4 expression.
- There is data in UC and bladder cancer variants showing co-existence of nectin-4 expression and programmed cell death 1 ligand 1 (PD-L1) expression and mismatch repair deficiency.
- There is currently very limited data on the level of nectin-4 expression in rare GU tumors and no evidence for the activity of EV in these tumors.
Objective:
-To assess the objective response rate (ORR) per RECIST v 1.1 in participants with rare genitourinary (GU) tumors treated with enfortumab vedotin (EV) with or without pembrolizumab.
Eligibility:
- Age >= 18 years
- Histologically confirmed diagnosis of locally advanced or metastatic pure adenocarcinoma of the urinary tract, pure squamous cell carcinoma of the urinary tract, or treatment-refractory testicular germ cell tumors.
- Participants may have received any number of prior anti-cancer treatments or be treatment na(SqrRoot) ve (with the exception of participants with testicular germ cell tumors, who must have exhausted all standard curative-intent options).
Design:
- This multisite study is a Phase II, open label, multicohort, nonrandomized study with two arms.
- Participants with:
- Adenocarcinoma of the urinary tract will be enrolled in Cohort A (Cohort A1: prior anti-1/PD-L1 therapy; Cohort A2: no prior anti-PD-1/PD-L1 therapy).
- Squamous cell carcinoma of the urinary tract will be enrolled in Cohort B (Cohort B1: prior anti-PD-1/PD-L1 therapy; Cohort B2: no prior anti-PD-1/PD-L1 therapy).
- Testicular germ cell tumors will be enrolled in Cohort C (Cohort C1: prior anti-PD-1/PDL1 therapy; Cohort C2: no prior anti-PD-1/PD-L1 therapy).
- All participants will receive EV.
- Participants without prior immune checkpoint inhibitor (ICI) exposure will be eligible to receive concurrent pembrolizumab.
- Arm 1: EV monotherapy will be given in 28-day cycles for a maximum of 5 years, or until disease progression or intolerable side effects. EV will be administered I.V. at 1.25 mg/kg on days 1, 8, and 15 of each cycle.
- Arm 2: EV and pembrolizumab will be given in 21-day cycles. EV will be administered I.V. at 1.25 mg/kg on days 1 and 8 of each cycle. Pembrolizumab will be administered I.V. at 200 mg on day 1.
- EV and pembrolizumab will be given for 35 cycles, or until a confirmed complete response, disease progression or intolerable side effects.
- After the 35th cycle, EV may be continued to be given for a maximum of 5 years, or until disease progression or intolerable side effects.
- Participants who have completed 35 cycles of pembrolizumab or stopped pembrolizumab for confirmed complete response may be eligible for up to additional 17 cycles of pembrolizumab if there is investigator-determined progressive disease by RECIST 1.1 after initial treatment.
- The accrual ceiling will be set at 68 participants to allow for inevaluable participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Enfortumab vedotinTreatment with enfortumab vedotin |
| Arm 2 | Experimental | Drug: Pembrolizumab, Drug: Enfortumab vedotinTreatment with enfortumab vedotin and pembrolizumab |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Participants must have histologically confirmed locally advanced or metastatic pure adenocarcinoma of the urinary tract, pure squamous cell carcinoma of the urinary tract, or treatment-refractory testicular germ cell tumors. Note: For the purposes of enrollment, the urinary tract is defined as the renal pelvis, ureter, bladder, and urethra.
- Participants must have measurable disease, per RECIST 1.1.
- Participants must have locally advanced or metastatic disease defined as new or progressive lesions on cross sectional imaging.
- Participants in Cohorts A1, B1, and C1 must have received prior anti-PD-1/PD-L1 therapy in any setting.
- Participants in Cohorts A2, B2, and C2 must be immune checkpoint inhibitor naive.
Key exclusion criteria (16 listed)
- Participants with prior investigational drug, chemotherapy, immunotherapy, or any prior radiotherapy (except for palliative bone directed therapy) within the past 2 weeks prior to the first study drug administration. Note: FDA-approved hormonal therapy for the treatment or prevention of other malignancies (e.g., breast cancer, prostate cancer) are allowed to be continued where in the opinion of the investigator stopping such therapies may increase the risk of disease progression. Potential drug-drug interactions with the hormonal agent will be assessed by the investigator prior to enrollment.
- Participants with prior treatment with EV or other MMAE-based ADCs.
- Participants with preexisting sensory or motor neuropathy Grade >= 2.
- History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to EV and/or pembrolizumab.
- Symptomatic or untreated central nervous system (CNS) metastases. Note: Participants with previously treated brain or CNS metastases are eligible if the participants have recovered from any acute effects of radiotherapy and not requiring steroids, and any whole brain radiation therapy or any stereotactic radiosurgery was completed at least 2 weeks prior to initiation of study therapy.
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 |
|---|---|---|
| PembrolizumabPembrolizumab is administered IV at 200 mg on day 1 of each 21-day cycle. | Drug | Arm 2 |
| Enfortumab vedotinEV is administered IV at 1.25 mg/kg on days 1, 8, and 15 of each 28-day cycle (Arm 1) and on days 1 and 8 of each 21-day cycle (Arm 2). | Drug | Arm 1, Arm 2 |
Primary outcome
Objective response rate (ORR)
Time frame: At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD
Percentage of participants by best overall response (e.g., CR, PR, SD, PD) to therapy
6 secondary outcomes
Second Objective response rate (ORR2) and second progression-free survival (PFS2) after second course of pembrolizumab
Time frame: At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD
Duration of response (DoR)
Time frame: At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD
Overall survival (OS)
Time frame: Day 1 of each cycle, at EoT, at the Safety visits, and every 90 days for up to a total of 5 years after the end of therapy.
Progression-free survival (PFS)
Time frame: At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD
Clinical benefit rate (CBR)
Time frame: At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD
Safety of EV with or without pembrolizumab
Time frame: From first dose through 30 days after last treatment with EV and 90 days after last treatment with pembrolizumab
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 13 Aug 2026.
- Derived from this study: PubMed 40421891Chandran EBA, Atiq S, Simon N, Girardi D, Ley L, Cordes L, Patel R, Wang TF, Kydd AR, Redd B, Boudjadi S, Stukes I, Banday R, Smith E, Akbulut D, Niglio S, Gurram S, Steinberg S, Apolo AB. E-VIRTUE: a study of enfortumab vedotin with or without pembrolizumab in rare genitourinary tumors-design and rationale. Future Oncol. 2025 Jun;21(13):1625-1630. doi: 10.1080/14796694.2025.2497719. Epub 2025 May 27.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All collected IPD will be shared
Related trials for Adenocarcinoma of the Bladder
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer
RecruitingPhase 2
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
Bladder Adenocarcinoma, Bladder Clear Cell Adenocarcinoma
Active, not recruiting
Medtronic Hugo™ Robotic Assisted Surgery (RAS) System in Urologic Surgery (Expand URO)
Bladder Cancer, Prostate Cancer
Active, not recruitingPhase 1
Study of AB598 Monotherapy and Combination Therapy in Participants With Advanced Cancers
Advanced Cancer, Advanced Malignancies
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.
Andrea B Apolo, M.D. principal investigator
National Cancer Institute (NCI)
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 and Enfortumab vedotin in people with Adenocarcinoma of the Bladder and Squamous Cell Carcinoma of the Bladder, run by National Cancer Institute (NCI) 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 23 inclusion and 16 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 13 Aug 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 Tzu-Fang Wang, R.N. ((240) 858-3236, tzu-fang.wang@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) (time frame: At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06041503, which also lists 1 linked publication.
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 13 Aug 2026.