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Bladder Squamous Cell CarcinomaPhase 2NCT05756569

Enfortumab Vedotin Plus Pembrolizumab for the Treatment of Locally Advanced or Metastatic Bladder Cancer of Variant Histology

A Phase 2 study testing Biospecimen Collection, Computed Tomography and Enfortumab Vedotin in people with Bladder Squamous Cell Carcinoma and Locally Advanced Bladder Carcinoma, run by Emory University at 4 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record

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Trial summary

This phase II trial tests how well enfortumab vedotin (EV) and pembrolizumab works in treating patients with bladder cancer of variant histology (a group of less common types of bladder cancer) that have spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Computed Tomography and Enfortumab Vedotin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
4 sitesUnited States
Study dates
26 Sep 2023to 16 Dec 2027
Phase
Phase 2

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

  • Male or Female
  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Metastatic disease or unresectable locally advanced disease
  • Histologically documented variant histology (nested, microcytic, micropapillary, lymphoepithelioma-like, plasmacytoid, giant cell, poorly differentiated, lipid-rich, clear cell, sarcomatoid) bladder cancer and non-urothelial bladder cancer of epithelial origin including squamous cell carcinoma and adenocarcinoma (urachal and non-urachal). Variant histology tumors and non-urothelial tumors of ureter, urethra, urachus, or renal pelvis are included. Patients with mixed cell type are eligible if the predominant histology (over 50%) is variant or non-urothelial. All histological classifications will follow the 2016 WHO Classifications.
  • Untreated or having received any number of lines of prior therapy
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  • Tumor tissue samples must be available for submission prior to initiation of study treatment. If not, agree to undergo biopsy
  • Patients must have measurable disease as defined by RECIST criteria 1.1 as at least one lesion that can be accurately measured in at least one dimension (longest diameter of >= 10 mm for non-nodal lesions or short axis of >= 15 mm for nodal lesions) on CT scan, MRI
  • Patients must have adequate organ and marrow function, within 28 days of cycle 1 day 1, at the discretion of the investigator
  • The effects of study drugs on the developing human fetus are unknown. For this reason, female of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy
  • FCBP and men treated or enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Additionally, FCBP and male subjects should use effective contraception for 6 months after the last dose. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Male subjects must not donate sperm and female subjects must not donate ova from screening to 6 months after the last dose
  • A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer >= 4 weeks before the start of study therapy
  • Life expectancy > 12 weeks as determined by the Investigator
  • Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions
  • Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation

Who cannot join

  • The neuroendocrine histology (small cell and large cell carcinomas) and non-epithelial bladder tumors (e.g. bladder sarcoma, carcinosarcoma, paraganglioma, melanoma, primary lymphoma, and lymphoepithelioma-like carcinoma) are excluded.
  • Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier [i.e. ongoing clinically significant toxicity (grade 2 or higher with the exception of alopecia) associated with prior treatment]
  • Patients who are receiving any other investigational agents or an investigational device within 21 days before administration of first dose of study drugs
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in study
  • Patients with ongoing sensory or motor neuropathy grade >= 2
  • Prior treatment or enrollment in a study with EV or PD1/PD-L1 immune checkpoint inhibitor (including maintenance therapy)
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  • Known uncontrolled diabetes mellitus with glycated hemoglobin (HbA1c) >= 8% or HbA1c 7% to < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained
  • Active central nervous system (CNS) metastases
  • Excluding the primary tumor leading to enrollment in this study, any other active malignancy (except for localized prostate cancer, definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the bladder or cervix) within the past 24 months
  • Currently receiving systemic antimicrobial treatment for active infection or high dose steroids (> 10mg of prednisone or equivalent)
  • A FCBP who has a positive urine pregnancy test at baseline or within 72 hours prior to receiving first study dose. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Breastfeeding females
  • History of active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs), known hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive), known active hepatitis C virus (defined as HCV ribonucleic acid [mRNA] [qualitative] is detected) or tuberculosis
  • History of active keratitis or corneal ulcerations
  • History of allogenic tissue/solid organ transplant
  • Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias within 6 months prior to first dose of EV/pembrolizumab
  • Other uncontrolled current illness including, but not limited to, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements

Trial locations and contacts

4 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Jacqueline Brown, MD contact

404-778-1900

jacqueline.theresa.brown@emory.edu

United States4 sites, 4 recruiting

  • Grady Health System

    Atlanta, Georgia, 30303

    Wilena Session, 404-778-4005, wsessio@emory.edu

    Jacqueline Brown, MD

    Recruiting

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

    Wilena Session, 404-778-4005, wsessio@emory.edu

    Jacqueline Brown, MD

    Recruiting

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

    Wilena Session, 404-778-4005, wsessio@emory.edu

    Jacqueline Brown, MD

    Recruiting

  • Emory Saint Joseph's Hospital

    Atlanta, Georgia, 30342

    Wilena Session, 404-778-4005, wsessio@emory.edu

    Jacqueline Brown, MD

    Recruiting

Other trials in United States

About this study

Official title: Phase II Single-Arm Study of Enfortumab Vedotin (EV) Plus Pembrolizumab in the Treatment of Locally Advanced or Metastatic Bladder Cancer of Variant Histology

This phase II trial tests how well enfortumab vedotin (EV) and pembrolizumab works in treating patients with bladder cancer of variant histology (a group of less common types of bladder cancer) that have spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. Enfortumab attaches to a protein called nectin-4 on cancer cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving enfortumab vedotin and pembrolizumab may kill more tumor cells in patients with locally advanced or metastatic bladder cancer of variant histology.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the anti-tumor activity of the combination of enfortumab vedotin (EV) plus pembrolizumab by assessing the overall response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

SECONDARY OBJECTIVES:

  1. To evaluate the efficacy of the combination as measured by progression free survival, overall survival, and duration of response.

II. To evaluate the safety as measured by incidence of adverse events assessed up to 2 years.

EXPLORATORY OBJECTIVE:

  1. To assess tissue-based assays in archival tissue and correlative changes in peripheral T-cell subsets, myeloid derived suppressor cells (MDSC), blood inflammatory markers and cytokines.

OUTLINE:

Patients receive enfortumab vedotin intravenously (IV) and pembrolizumab IV on study. Patients also undergo computed tomography (CT) scan or magnetic resonance imaging (MRI), and collection of blood throughout the trial.

Being tested
Biospecimen Collection, Computed Tomography, Enfortumab Vedotin, Magnetic Resonance Imaging, Pembrolizumab
Medical subject headings
Ureteral Neoplasms, Urinary Bladder Neoplasms, Urachal adenocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo collection of blood

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • Enfortumab VedotinDrug

    Also called AGS 22ME, AGS-22M6E, Anti-Nectin 4 ADC ASG-22CE, Anti-nectin-4 Monoclonal Antibody-Drug Conjugate AGS-22M6E

    Given IV

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR

    Undergo MRI

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT05756569
Study groupRoleWhat they receive
Treatment (enfortumab vedotin, pembrolizumab)ExperimentalPatients receive enfortumab vedotin IV and pembrolizumab IV on study. Patients also undergo CT scan or MRI, and collection of blood throughout the trial.
Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Enfortumab Vedotin; Procedure: Magnetic Resonance Imaging; Biological: Pembrolizumab; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall response rate

    Will be measured by Response Evaluation Criteria in Solid Tumors version 1.1, and estimated by the Clopper-Pearson method with 95% confidence intervals.

    Measured: Up to 2 years

Secondary outcomes (4)

  1. Progression free survival

    Kalan-Meier method will be used to estimate median event time and 2-year survival rate with 95% confidence interval.

    Measured: From treatment initiation until disease progression or death due to any cause, assessed up to 2 years

  2. Overall survival

    Kalan-Meier method will be used to estimate median event time and 2-year survival rate with 95% confidence interval.

    Measured: From treatment initiation until death due to any cause, assessed up to 2 years

  3. Duration of response

    Determined by occurrence of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.

    Measured: From response initiation to progression or death, whichever occurs first, assessed up to 2 years

  4. Incidence of adverse events

    Graded according to the Common Terminology Criteria for Adverse Events version 5.0, and will be tabulated using descriptive statistics (mean, median, minimum, maximum, standard deviation).

    Measured: Assessed up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Mar 2023
  2. Study start26 Sep 2023
  3. Primary completion16 Dec 2026 (estimated)
  4. Study completion16 Dec 2027 (estimated)

Resources

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)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05756569
Sponsor's protocol ID
STUDY00005143
Other IDs
NCI-2023-00104, STUDY00005143, WINSHIP5742-22, P30CA138292
Status last verified
Jul 2026
First submitted
20 Feb 2023
Last updated
29 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

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