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AzTrials

Carcinoma, Transitional CellPhase 1/2EV-103NCT03288545

A Study of Enfortumab Vedotin Alone or With Other Therapies for Treatment of Urothelial Cancer

A Phase 1/2 study testing enfortumab vedotin (EV), pembrolizumab and cisplatin in people with Carcinoma, Transitional Cell and Urinary Bladder Neoplasms, run by Astellas Pharma Global Development, Inc. at 106 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study will test an experimental drug (enfortumab vedotin) alone and with different combinations of anticancer therapies. Pembrolizumab is an immune checkpoint inhibitor (CPI) that is used to treat patients with cancer of the urinary system (urothelial cancer). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
enfortumab vedotin (EV), pembrolizumab and cisplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
348 participants
Where
106 sitesin 6 countries
Study dates
11 Oct 2017to 20 Feb 2026
Phase
Phase 1/2
Are there results?
None posted in the registry

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

  • Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K.
  • Histologically documented la/mUC, including squamous differentiation or mixed cell types.
  • An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2: Participants with ECOG performance status of 2 must meet the following additional criteria: hemoglobin ≥10 g/dL, GFR ≥50 mL/min, may not have NYHA Class III heart failure.
  • Eligible for pembrolizumab (Dose-escalation cohorts, Cohorts A, B, G and K Combination Arm).
  • Dose-escalation cohorts: Ineligible for first-line cisplatin-based chemotherapy and no prior treatment for la/mUC, or have disease progression following at least 1 platinum-containing treatment.
  • Cohort A: Ineligible for cisplatin-based chemotherapy and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
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  • Cohort B: Must have disease progression during/following treatment with at least 1 platinum-containing regimen for la/mUC or disease recurrence.
  • Cohort D: Eligible for cisplatin-based chemotherapy and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
  • Cohort E: Ineligible for cisplatin-based chemotherapy, eligible for carboplatin, and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
  • Cohort F: Ineligible for platinum-based chemotherapy, or disease progression during/following at least 1 prior treatment for la/mUC. Eligible for gemcitabine.
  • Cohort G: Eligible for platinum-based chemotherapy (either cisplatin or carboplatin) and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
  • Cohort K: Ineligible for cisplatin-based chemotherapy due to at least 1 of the following: Glomerular filtration rate (GFR) <60 mL/min and ≥30 mL/min, ECOG performance status of 2, NCI CTCAE Version 4.03 Grade ≥2 hearing loss, New York Heart Association (NYHA) Class III heart failure. No prior systemic treatment for locally advanced or metastatic disease. No adjuvant/neoadjuvant platinum-based therapy within 12 months prior to randomization.
  • Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.
  • Histologically confirmed MIBC with predominant >50% urothelial histology: Cohorts H and J: Clinical stage cT2-T4aN0M0; Cohort L: Clinical stage cT2-T4aN0M0 or cT1-T4aN1M0: Participants with pT1 disease are eligible only if they have N1 disease on imaging. Mixed cell types are eligible if urothelial cancer is predominant (>50%); Participants with plasmacytoid and/or neuroendocrine tumors are ineligible regardless of component percentage. Urothelial tumors not originating in the bladder (eg, upper tract tumors, urethral tumors) are ineligible.
  • Must be cisplatin-ineligible.
  • Cohort-specific eligibility: Cohort J, H, and L: No prior systemic treatment, chemoradiation, or radiation therapy for MIBC. May have received prior intravesical Bacillus Calmette-Guerin (BCG) or intravesical chemotherapy for non-MIBC; Cohort J: Eligible for pembrolizumab.
  • ECOG performance status of 0, 1, or 2.
  • Anticipated life expectancy of ≥3 months.
  • Tumor samples with an associated pathology report from the diagnostic transurethral resection of a bladder tumor done 90 days prior to the first dose of study treatment must be available prior to enrollment and determined to be sufficient for pathology review and biomarker analysis.
  • Participants must be deemed eligible for RC+PLND.

Who cannot join

  • la/mUC - Cohorts A, B, D, E, F, G, and K
  • Received any prior treatment with a PD-1 inhibitor, PD-L1 inhibitor, or PD-L2 inhibitor, except Cohort F.
  • Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, OX-40 agonists, or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors (except Cohort F).
  • Ongoing sensory or motor neuropathy Grade 2 or higher.
  • Active central nervous system (CNS) metastases.
  • Ongoing clinically significant toxicity (Grade 2 or greater) associated with prior treatment (including radiotherapy or surgery).
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  • Conditions requiring high doses of steroids or other immunosuppressive medications.
  • Prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
  • Uncontrolled diabetes mellitus.
  • MIBC - Cohorts H, J, and L
  • Received prior systemic treatment, chemoradiation, and/or radiation therapy of muscle invasive bladder cancer.
  • Received any prior treatment with a CPI.
  • Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, CTLA-4 inhibitors, or OX-40 agonists.
  • For participants in Cohort H, evidence of nodal disease on imaging. For participants in Cohort L, ≥N2 nodal disease on imaging.
  • Participant has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC.
  • Ongoing sensory or motor neuropathy Grade 2 or higher.
  • Conditions requiring high doses of steroids or other immunosuppressive medications.
  • Prior treatment with enfortumab vedotin or other MMAE-based ADCs for urothelial cancer.
  • Participants with a history of another invasive malignancy within 3 years before first dose of study drug.

Trial locations and contacts

106 sites in 6 countries.

106 sites in 6 countries

United States83 sites

  • New York Oncology Hematology, P.C.

    Albany, New York, 12206

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • Alaska Urological Institute

    Anchorage, Alaska, 99503

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • Piedmont Cancer Institute

    Atlanta, Georgia, 30309

  • Winship Cancer Institute / Emory University School of Medicine

    Atlanta, Georgia, 30322

  • Rocky Mountain Cancer Centers - Aurora

    Aurora, Colorado, 80012

  • University of Colorado Hospital / University of Colorado

    Aurora, Colorado, 80045-0510

  • Memorial Sloan Kettering Cancer Center - Basking Ridge

    Basking Ridge, New Jersey, 07920

  • Tower Hematology Oncology Medical Group

    Beverly Hills, California, 90211

  • Boca Raton Regional Hospital / Lynn Cancer Institute

    Boca Raton, Florida, 33486

  • CMOH Broomall

    Broomall, Pennsylvania, 19008

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Gabrail Cancer Center Research, LLC

    Canton, Ohio, 44718

  • UNC Lineberger Comprehensive Cancer Center / University of North Carolina

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina/Hollings Cancer Center

    Charleston, South Carolina, 29425

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

  • University of Virginia

    Charlottesville, Virginia, 22903

  • Sarah Cannon Research Institute

    Chattanooga, Tennessee, 37404

  • University of Chicago Medical Center

    Chicago, Illinois, 60637-1470

  • Case Western Reserve University / University Hospitals Case Medical Center

    Cleveland, Ohio, 44106

  • Memorial Sloan Kettering Cancer Center - Commack

    Commack, New York, 11725

  • Decatur Memorial Hospital - Illinois

    Decatur, Illinois, 62526

  • Northwestern Medicine Cancer Center - Kishwaukee / Kishwaukee Cancer Center

    DeKalb, Illinois, 60115

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Southcoast Centers for Cancer Care - Fairhaven Site

    Fairhaven, Massachusetts, 02719

  • Highlands Oncology Group

    Fayetteville, Arkansas, 72703

  • Holy Cross Hospital - Michael and Dianne Bienes Comprehensive Cancer Center

    Fort Lauderdale, Florida, 33308

  • Texas Oncology - Fort Worth Cancer Center

    Fort Worth, Texas, 76104

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • Vidant Medical Center

    Greenville, North Carolina, 27834

  • Saint Francis Hospital Cancer Center

    Greenville, South Carolina, 29607

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Memorial Sloan Kettering Cancer Center - Westchester

    Harrison, New York, 10604

  • Penn State Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39213

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

  • UC San Diego / Moores Cancer Center

    La Jolla, California, 92093

  • Northwell Cancer Center / Monter Cancer Center

    Lake Success, New York, 11042

  • McLaren Greater Lansing Hospital

    Lansing, Michigan, 48910

  • OptumCare Cancer Center

    Las Vegas, Nevada, 89102

  • Nebraska Hematology Oncology P.C.

    Lincoln, Nebraska, 68506

  • Cardinal Bernardin Cancer Center / Loyola University Medical Center

    Maywood, Illinois, 60153

  • University of Miami

    Miami, Florida, 33136

  • Memorial Sloan Kettering Cancer Center - Monmouth

    Middletown, New Jersey, 07748

  • Medical College of Wisconsin (Milwaukee)

    Milwaukee, Wisconsin, 53226

  • NYU Winthrop Hospital

    Mineola, New York, 11501

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Memorial Sloan Kettering Cancer Center - Bergen

    Montvale, New Jersey, 07645

  • Carolina Urologic Research Center

    Myrtle Beach, South Carolina, 29572

  • Tennessee Oncology / Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Yale Cancer Center

    New Haven, Connecticut, 06520

  • Tulane University Hospital and Clinic

    New Orleans, Louisiana, 70112

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

  • New York University (NYU) Cancer Institute

    New York, New York, 10016

  • Weill Cornell Medical College

    New York, New York, 10065

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10087-9049

  • Virginia Oncology Associates - Norfolk

    Norfolk, Virginia, 23502

  • Eastern CT Hematology and Oncology Associates

    Norwich, Connecticut, 06360

  • University of California Irvine - Newport

    Orange, California, 92868

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Mayo Clinic Arizona

    Phoenix, Arizona, 85054

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • University of Rochester Medical Center

    Rochester, New York, 14642

  • University of California, Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Utah Cancer Specialists

    Salt Lake City, Utah, 84106

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • University of California at San Francisco

    San Francisco, California, 94134

  • Saint Joseph Heritage Medical Group

    Santa Rosa, California, 95403

  • Maryland Oncology Hematology, P.A.

    Silver Spring, Maryland, 20904

  • Medical Oncology Associates

    Spokane, Washington, 99208

  • Washington University School of Medicine - Siteman Cancer Center

    St Louis, Missouri, 63110

  • Stanford Cancer Center / Blood & Marrow Transplant Program

    Stanford, California, 94305

  • Toledo Clinic Cancer Center

    Toledo, Ohio, 43623

  • Arizona Oncology Associates, PC - HOPE

    Tucson, Arizona, 85710

  • Texas Oncology - Tyler

    Tyler, Texas, 75702

  • Memorial Sloan Kettering Cancer Center - Nassau

    Uniondale, New York, 11553

  • Northwestern Medicine Cancer Center - Warrenville / Central DuPage Hospital - Cancer Care

    Warrenville, Illinois, 60555

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

  • University of Kansas Cancer Center

    Westwood, Kansas, 66205

  • Kaiser Permanente Southern California

    Woodland Hills, California, 91367

Other trials in United States

France8 sites

  • Site FR33008

    Bordeaux, 33000

  • Site FR33005

    Dijon, 21000

  • Site FR33003

    Lyon, 69008

  • Site FR33004

    Marseille, 13273

  • Site FR33010

    Moselle, 54519

  • Site FR33002

    Nice, 06189

  • Site FR33006

    Pierre-Bénite, 69310

  • Site FR33001

    Strasbourg, 67200

Other trials in France

Spain7 sites

  • Site ES34006

    Barcelona, 08041

  • Site ES34008

    Madrid, 28033

  • Site ES34001

    Madrid, 28034

  • Site ES34012

    Madrid, 28041

  • Site ES34007

    Pamplona, 31008

  • Site ES34005

    Sabadell, 08208

  • Site ES34004

    Santander, 39008

Other trials in Spain

Canada6 sites

  • Site CA11008

    East Brampton, Ontario, L6R 3J7

  • Site CA11011

    Kingston, Ontario, K7L 2V7

  • Site CA11005

    Montreal, Quebec, H3T1E2

  • Site CA11013

    Montreal, Quebec, H4A3J1

  • Site CA11002

    Sherbrooke, Quebec, J1H 5N4

  • Site CA11001

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Italy1 site

  • Site IT39002

    Terni, 05100

Other trials in Italy

Puerto Rico1 site

  • Site PR78701

    Rio Piedras, 00935

Other trials in Puerto Rico

About this study

Official title: A Study of Enfortumab Vedotin (ASG-22CE) as Monotherapy or in Combination With Other Anticancer Therapies for the Treatment of Urothelial Cancer

This study will test an experimental drug (enfortumab vedotin) alone and with different combinations of anticancer therapies. Pembrolizumab is an immune checkpoint inhibitor (CPI) that is used to treat patients with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra. Some parts of the study will look at locally advanced or metastatic urothelial cancer (la/mUC), which means the cancer has spread to nearby tissues or to other areas of the body. Other parts of the study will look at muscle-invasive bladder cancer (MIBC), which is cancer at an earlier stage that has spread into the muscle wall of the bladder. This study will look at the side effects of enfortumab vedotin alone and with other anticancer therapies. A side effect is a response to a drug that is not part of the treatment effect. This study will also test if the cancer shrinks with the different treatment combinations.

Read the detailed description

This study will examine the safety and anticancer activity of enfortumab vedotin (EV) given intravenously as monotherapy and in combination with other anticancer therapies as first line (1L) and second line (2L) treatment for patients with urothelial cancer. The primary goal of the study is to determine the safety, tolerability, and efficacy of enfortumab vedotin alone and in combination with pembrolizumab and/or chemotherapy. The study will be conducted in multiple parts:

Locally advanced or metastatic urothelial cancer:

  • Dose escalation
  • Expansion
  • Part 1: Cohorts A and Optional B
  • Part 2: Cohorts D, E, and Optional F
  • Part 3: Cohort G.
  • Randomized Cohort K
  • EV Monotherapy Arm
  • EV Combination Arm

Muscle invasive bladder cancer:

  • Cohort H
  • Optional Cohort J
  • Cohort L
Being tested
enfortumab vedotin (EV), pembrolizumab, cisplatin, carboplatin, gemcitabine
Keywords
ASG-22ME, ASG-22CE, Antibody-drug conjugate, Antineoplastic agents, CPI, Enfortumab vedotin, MIBC, Locally advanced urothelial cancer, Cisplatin, Drug therapy, Carboplatin, Metastatic urothelial cancer, Nectin-4, Gemcitabine, Muscle invasive bladder cancer, Checkpoint Inhibitors, Pembrolizumab, PD-1 inhibitor
Medical subject headings
Carcinoma, Transitional Cell, Urinary Bladder Neoplasms, Urologic Neoplasms, Ureteral Neoplasms, Urethral Neoplasms

What participants receive

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

  • enfortumab vedotin (EV)Drug

    Also called ASG-22CE, ASG-22ME, PADCEV

    Intravenous (IV) infusion on days 1 and 8 every 21 days

  • pembrolizumabDrug

    Also called Keytruda

    IV infusion on day 1 every 21 days

  • cisplatinDrug

    IV infusion on day 1 every 21 days

  • carboplatinDrug

    IV infusion on day 1 every 21 days

  • gemcitabineDrug

    IV infusion on days 1 and 8 every 21 days

Study groups in NCT03288545
Study groupRoleWhat they receive
EV + Pembrolizumab in cisplatin-ineligible 1L and in 2LExperimentalDose Escalation: Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
Receives: Drug: enfortumab vedotin (EV); Drug: pembrolizumab
Cohort A: EV + Pembrolizumab in cisplatin-ineligible 1LExperimentalEnfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
Receives: Drug: enfortumab vedotin (EV); Drug: pembrolizumab
Optional Cohort B: Enfortumab Vedotin + Pembrolizumab in 2LExperimentalEnfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
Receives: Drug: enfortumab vedotin (EV); Drug: pembrolizumab
Cohort D: Enfortumab Vedotin + Cisplatin in 1LExperimentalEnfortumab vedotin on days 1 and 8 plus cisplatin on day 1 every 21 days
Receives: Drug: enfortumab vedotin (EV); Drug: cisplatin
Cohort E: Enfortumab Vedotin + Carboplatin in 1LExperimentalEnfortumab vedotin on days 1 and 8 plus carboplatin on day 1 every 21 days
Receives: Drug: enfortumab vedotin (EV); Drug: carboplatin
Optional Cohort F: Enfortumab Vedotin+Gemcitabine in 1L and 2LExperimentalEnfortumab vedotin and gemcitabine on days 1 and 8 every 21 days
Receives: Drug: enfortumab vedotin (EV); Drug: gemcitabine
Cohort G: Enfortumab Vedotin + Platinum + Pembrolizumab in 1LExperimentalEnfortumab vedotin on days 1 and 8 plus cisplatin or carboplatin on day 1 plus pembrolizumab on day 1 every 21 days
Receives: Drug: enfortumab vedotin (EV); Drug: pembrolizumab; Drug: cisplatin; Drug: carboplatin
Cohort H: Enfortumab vedotin in MIBC neoadjuvant settingExperimentalEnfortumab vedotin on days 1 and 8 every 21 days
Receives: Drug: enfortumab vedotin (EV)
Optional Cohort J:EV+Pembrolizumab in MIBC neoadjuvant settingExperimentalEnfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
Receives: Drug: enfortumab vedotin (EV); Drug: pembrolizumab
Randomized Cohort K: Enfortumab Vedotin MonotherapyExperimentalEnfortumab vedotin on days 1 and 8 every 21 days
Receives: Drug: enfortumab vedotin (EV)
Randomized Cohort K: Enfortumab Vedotin + PembrolizumabExperimentalEnfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
Receives: Drug: enfortumab vedotin (EV); Drug: pembrolizumab
Cohort L: Enfortumab vedotin in MIBC in perioperative settingExperimentalEnfortumab vedotin on days 1 and 8 and every 21 days
Receives: Drug: enfortumab vedotin (EV)

What is being measured

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

  1. Type, incidence, severity, seriousness, and relatedness of adverse events (Dose escalation and Expansion Parts 1 to 3 cohorts only)

    Descriptive statistics will be used to summarize results.

    Measured: Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated.

  2. Type, incidence, and severity of laboratory abnormalities (Dose escalation and Expansion Parts 1 to 3 cohorts only)

    Descriptive statistics will be used to summarize results.

    Measured: Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated.

  3. Confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR) (Cohort K only)

    The proportion of patients with confirmed complete response (CR) or partial response (PR) according to RECIST 1.1

    Measured: Up to 3 years

  4. Pathological complete response (pCR) rate per central pathology review (MIBC cohorts only)

    The proportion of patients with absence of viable tumor tissue at the time of radical cystectomy.

    Measured: Up to approximately 5 months

Secondary outcomes (32)

  1. Incidence of dose-limiting toxicity (DLT)

    Incidence of DLTs (dose-escalation expansion Cohorts D, E, F, and the first 6 patients of Cohort G).

    Measured: 21 days

  2. Confirmed ORR by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)

    The proportion of patients with confirmed CR or PR according to RECIST 1.1.

    Measured: Up to 3 years

  3. Confirmed ORR by BICR according to RECIST 1.1 (Dose escalation and Cohort A only)

    The proportion of patients with confirmed CR or PR according to RECIST 1.1

    Measured: Up to 3 years

  4. Confirmed ORR by investigator assessment per the modified RECIST 1.1 for immune-based therapeutics (iRECIST) (Dose escalation and Part 1-3 cohorts with pembrolizumab only)

    The proportion of patients with confirmed CR or PR according to iRECIST.

    Measured: Up to 3 years

  5. Disease control rate (DCR) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)

    Proportion of patients with CR, PR, or stable disease (SD) according to RECIST 1.1.

    Measured: Up to 5 years

  6. DCR by BICR according to RECIST 1.1 (Dose escalation, Cohort A, and randomized Cohort K only)

    Proportion of patients with CR, PR, or stable disease (SD) according to RECIST 1.1

    Measured: Up to 3 years

  7. DCR by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts using pembrolizumab only)

    Proportion of patients with CR, PR, or SD according to iRECIST.

    Measured: Up to 3 years

  8. Duration of response (DOR) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)

    The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease (PD per RECIST 1.1) or to death due to any cause, whichever comes first.

    Measured: Up to 5 years

  9. DOR by BICR according to RECIST 1.1 (Dose escalation, Cohort A, and randomized Cohort K only)

    The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD per RECIST 1.1 or to death due to any cause, whichever comes first

    Measured: Up to 5 years

  10. DOR by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts with pembrolizumab only)

    The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD per iRECIST or to death due to any cause, whichever comes first.

    Measured: Up to 5 years

  11. Progression free survival on study therapy (PFS) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)

    The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1) on or following study therapy, or to death due to any cause, whichever comes first.

    Measured: Up to 5 years

  12. PFS by BICR according to RECIST 1.1 (Dose escalation, Cohort A, and randomized Cohort K only)

    The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1) on or following study therapy, or to death due to any cause, whichever comes first

    Measured: Up to 5 years

  13. PFS by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts with pembrolizumab only)

    The time from start of study treatment to first documentation of objective tumor progression (PD per iRECIST) on or following study therapy, or to death due to any cause, whichever comes first.

    Measured: Up to 5 years

  14. Event-free (EFS) on study therapy by BICR (Cohort L only)

    The time from the start of study treatment to the first occurrence of any of the following events: (1) Radiographic disease progression precluding a curative intent surgery as assessed by BICR prior to RC+PLND. (2) Failure to undergo RC+PLND for participants with residual muscle-invasive disease and/or any radiographic disease present. (3) Gross residual disease left behind at time of RC+PLND. (4) Local or distant recurrence post-RC as assessed by CT or MRI and/or biopsy. (5) Death from any cause.

    Measured: Up to 3 years

  15. Event-free (EFS) on study therapy by investigator assessment (MIBC cohorts only)

    The time from the start of study treatment to the first occurrence of any of the following events: (1) Radiographic disease progression precluding a curative intent surgery as assessed by BICR prior to RC+PLND. (2) Failure to undergo RC+PLND for participants with residual muscle-invasive disease and/or any radiographic disease present. (3) Gross residual disease left behind at time of RC+PLND. (4) Local or distant recurrence post-RC as assessed by CT or MRI and/or biopsy. (5) Death from any cause.

    Measured: Up to 3 years

  16. Overall survival (OS) (all cohorts)

    The time from start of study treatment to date of death due to any cause.

    Measured: Up to 5 years

  17. Pharmacokinetics (PK) parameter for enfortumab vedotin: Maximum concentration (Cmax) (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)

    Cmax will be derived from the PK blood samples collected.

    Measured: Through 2 cycles of treatment, up to 42 days

  18. PK parameter for monomethyl auristatin E (MMAE): Cmax (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)

    Cmax will be derived from the PK blood samples collected.

    Measured: Through 2 cycles of treatment, up to 42 days

  19. PK parameter for total antibody (Tab): Cmax (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)

    Cmax will be derived from the PK blood samples collected.

    Measured: Through 2 cycles of treatment, up to 42 days

  20. Incidence of antitherapeutic antibodies (ATA) to enfortumab vedotin (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)

    Blood samples for ATA analysis will be collected.

    Measured: Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated.

  21. PK parameter for enfortumab vedotin: Time to maximum concentration (Tmax) (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)

    Tmax will be derived from the PK blood samples collected.

    Measured: Through 2 cycles of treatment, up to 42 days

  22. PK parameter for MMAE: Tmax (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)

    Tmax will be derived from the PK blood samples collected.

    Measured: Through 2 cycles of treatment, up to 42 days

  23. PK parameter for Tab: Tmax (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)

    Tmax will be derived from the PK blood samples collected.

    Measured: Through 2 cycles of treatment, up to 42 days

  24. PK parameter for enfortumab vedotin: Area under the concentration-time curve (AUC) (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)

    AUC will be derived from the PK blood samples collected.

    Measured: Through 2 cycles of treatment, up to 42 days

  25. PK parameter for MMAE: AUC (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)

    AUC will be derived from the PK blood samples collected.

    Measured: Through 2 cycles of treatment, up to 42 days

  26. PK parameter for Tab: AUC (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)

    AUC will be derived from the PK blood samples collected.

    Measured: Through 2 cycles of treatment, up to 42 days

  27. Pathologic downstaging (pDS) rate by central pathology review (MIBC cohorts only)

    The pDS rate is defined as patients with tumors <pT2 and N0 in examined tissue from radical cystectomy (RC) and pelvic lymph node dissection (PLND).

    Measured: Up to approximately 5 months

  28. Disease-free survival (DFS) by investigator assessment (MIBC cohorts only)

    DFS is defined as the time from RC to the time of first occurrence of a DFS event, including local recurrence of urothelial cancer (UC), urinary tract recurrence of UC, distant metastasis of UC, or death from any cause.

    Measured: Up to approximately 5 years

  29. DFS by BICR (Cohort L only)

    DFS is defined as the time from RC to the time of first occurrence of a DFS event

    Measured: Up to 3 years

  30. Type, incidence, severity, seriousness, and relatedness of AEs (Randomized Cohort K and MIBC cohorts only)

    Descriptive statistics will be used to summarize results.

    Measured: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to approximately 3 years

  31. Type, incidence, and severity of laboratory abnormalities (Randomized Cohort K and MIBC cohorts only)

    Descriptive statistics will be used to summarize results.

    Measured: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to approximately 3 years

  32. Percentage of planned radical cystectomy and pelvic lymph node dissections (RC+PLND) delayed due to treatment-related AEs (MIBC cohorts only)

    Delayed is defined as greater than 12 weeks after the last dose of treatment.

    Measured: Up to approximately 5 months

Timeline

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

  1. First posted20 Sep 2017
  2. Study start11 Oct 2017
  3. Primary completion20 Feb 2026
  4. Study completion20 Feb 2026

Why it stopped: Sponsor stopped the study after meeting enrollment targets and primary objectives, and after collecting sufficient data for planned regulatory filings. The decision was not due to safety concerns, futility, or any regulatory request.

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
multi-cohort, open-label, multicenter study, global
Masking
None (open label)
Enrolment
348 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03288545
Sponsor's protocol ID
SGN22E-002
Other IDs
MK-3475-869, KEYNOTE KN-869
Acronym
EV-103
Status last verified
Mar 2026
First submitted
18 Sep 2017
Last updated
24 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided
Expanded access
Available

Publications

  • Milowsky MI, O'Donnell PH, Hoimes CJ, Petrylak DP, Flaig TW, Moon HH, Friedlander TW, Mar N, McKay RR, Srinivas S, Gravis G, Ramamurthy C, Bupathi M, Bracarda S, Wright P, Hepp Z, Carret AS, Yu Y, Dillon R, Kataria R, Beaumont JL, Purnajo I, Rosenberg JE. Patient-Reported Outcomes in Patients With Advanced Urothelial Cancer Who Are Ineligible for Cisplatin and Treated With First-Line Enfortumab Vedotin Alone or With Pembrolizumab. J Clin Oncol. 2024 Apr 20;42(12):1403-1414. doi: 10.1200/JCO.23.01547. Epub 2024 Jan 12.

    PubMed 38215355

  • O'Donnell PH, Milowsky MI, Petrylak DP, Hoimes CJ, Flaig TW, Mar N, Moon HH, Friedlander TW, McKay RR, Bilen MA, Srinivas S, Burgess EF, Ramamurthy C, George S, Geynisman DM, Bracarda S, Borchiellini D, Geoffrois L, Maroto Rey JP, Ferrario C, Carret AS, Yu Y, Guseva M, Homet Moreno B, Rosenberg JE. Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. J Clin Oncol. 2023 Sep 1;41(25):4107-4117. doi: 10.1200/JCO.22.02887. Epub 2023 Jun 27.

    PubMed 37369081

  • Hoimes CJ, Flaig TW, Milowsky MI, Friedlander TW, Bilen MA, Gupta S, Srinivas S, Merchan JR, McKay RR, Petrylak DP, Sasse C, Moreno BH, Yu Y, Carret AS, Rosenberg JE. Enfortumab Vedotin Plus Pembrolizumab in Previously Untreated Advanced Urothelial Cancer. J Clin Oncol. 2023 Jan 1;41(1):22-31. doi: 10.1200/JCO.22.01643. Epub 2022 Aug 30.

    PubMed 36041086

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing enfortumab vedotin (EV), pembrolizumab and cisplatin in people with Carcinoma, Transitional Cell and Urinary Bladder Neoplasms, run by Astellas Pharma Global Development, Inc. at 106 sites in 6 countries.

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 20 inclusion and 19 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: stopped early, as of the sponsor's last update on 24 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 106 sites in United States, France, Spain, Canada, Italy and 1 more country. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The study was stopped early (reason given: Sponsor stopped the study after meeting enrollment targets and primary objectives, and after collecting sufficient data for planned regulatory filings. The decision was not due to safety concerns, futility, or any regulatory request.). Results are not available in the source record.

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?

Type, incidence, severity, seriousness, and relatedness of adverse events (Dose escalation and Expansion Parts 1 to 3 cohorts only) (time frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated.). 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?

On the ClinicalTrials.gov record for NCT03288545, which also lists 3 linked publications.

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 24 Mar 2026.

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