Enfortumab Vedotin With or Without Pembrolizumab in Rare Genitourinary Tumors (E-VIRTUE)

NCT06041503 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10001533001533-C
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief 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. 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.

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

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  Percentage of participants by best overall response (e.g., CR, PR, SD, PD) to therapy

  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

  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)

  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)

  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)

  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)

  At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD

Study Arms (2)

Arm 1

EXPERIMENTAL

Treatment with enfortumab vedotin

Drug: Enfortumab vedotin

Arm 2

EXPERIMENTAL

Treatment with enfortumab vedotin and pembrolizumab

Drug: Pembrolizumab; Drug: Enfortumab vedotin

Interventions

Pembrolizumab DRUG

Pembrolizumab is administered IV at 200 mg on day 1 of each 21-day cycle.

Arm 2

Enfortumab vedotin DRUG

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).

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 40421891 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

pembrolizumab; enfortumab vedotin

Study Officials

• Andrea B Apolo, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lisa Ley, R.N.

CONTACT

(240) 858-3524; lisa.ley@nih.gov

Andrea B Apolo, M.D.

CONTACT

(301) 480-0536; apoloab@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2023
• First Posted: September 18, 2023
• Study Start: January 20, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: January 23, 2026

Record last verified: 2026-01-16

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data from this study may be requested from other researchers at least 1 year after the completion of the primary endpoint.
• Access Criteria: Data from this study may be requested by contacting the PI.

Locations

US (1)