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Metastatic Urothelial Cancer and Other Malignant Solid TumorsPhase 1NCT02091999

A Study of Escalating Doses of ASG-22CE Given as Monotherapy in Subjects With Metastatic Urothelial Cancer and Other Malignant Solid Tumors That Express Nectin-4

A Phase 1 study testing enfortumab vedotin in people with Metastatic Urothelial Cancer and Other Malignant Solid Tumors, run by Astellas Pharma Global Development, Inc. at 21 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate the safety and pharmacokinetics of enfortumab vedotin as well as assess the immunogenicity and antitumor activity in subjects with metastatic urothelial cancer and other malignant solid tumors that express Nectin-4. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
enfortumab vedotin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
213 participants
Where
21 sitesin 2 countries
Study dates
14 May 2014to 7 Dec 2022
Phase
Phase 1
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

  • Dose Escalation, Renal insufficiency and CPI-Treated Expansion cohorts: Histologically confirmed Transitional Cell Carcinoma of the Urothelium (TCCU) (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with Urothelial Carcinoma with squamous differentiation or mixed cell types are eligible.
  • Ovarian Expansion Cohort: Subjects with recurrent disease or histologically or cytologically confirmed Stage III/IV diagnosis of epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal carcinoma who have previously progressed while receiving or within 6 months of completing a platinum-containing regimen.
  • NSCLC Expansion Cohort: Histologic or cytologic diagnosis of NSCLC (squamous or non-squamous or NSCLC-not specified)
  • Dose Escalation, Renal insufficiency, NSCLC and CPI-Treated Expansion Cohorts: For subjects with urothelial cancer and NSCLC: Subjects must submit a tumor tissue for Nectin-4 expression. Enrollment for these subjects is not dependent on the immunohistochemistry using the H-Score (IHC H-Score).
  • Ovarian Expansion Cohort: Subjects must have tumor tissue positive (IHC H-score ≥150) for Nectin-4 expression
  • For Dose Escalation, NSCLC and Ovarian Expansion Cohorts: Subject must have failed at least one prior chemotherapy regimen for metastatic disease (urothelial and bladder cancer subjects are not required to have failed prior chemotherapy regimen if considered unfit for cisplatin-based chemotherapy)
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  • For the CPI-Treated Expansion Cohort: Subject must have received prior treatment with a CPI in the metastatic setting.
  • Subjects must have measurable disease according to RECIST (version 1.1)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy of ≥ 3 months
  • Negative pregnancy test (women of childbearing potential)
  • Hematologic function, as follows (no red blood cell or platelet transfusions are allowed within 14 days of the first dose of enfortumab vedotin):
  • Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • Hemoglobin ≥ 9 g/dL
  • Renal function, as follows: Dose Escalation, NSCLC, Ovarian, and CPI Treated Expansion Cohorts: creatinine clearance of ≥ 30 mL/min by the Cockcroft-Gault equation or as measured by 24 hour urine collection. For the Renal Insufficiency Expansion Cohort: creatinine clearance estimate ≥15 ml/min and <30 ml/min by Cockcroft-Gault equation or as measured by 24 hour urine collection.
  • Total bilirubin ≤ 1.5 x ULN (upper limit of normal)
  • Serum albumin ≥2.5 g/dL
  • Aspartate aminotransferase (AST) ≤ 1.5 x ULN
  • Alanine aminotransferase (ALT) ≤ 1.5 x ULN
  • International normal ratio (INR) < 1.3 or ≤ institutional ULN (or ≤ 3.0 if on therapeutic anticoagulation)
  • Sexually active fertile subjects, and their partners, must agree to use medically accepted double-barrier methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the study and at least 6 months after termination of study therapy
  • Competent to comprehend, sign, and date an independent ethics committee/institutional review board/research ethics board (IEC/IRB/REB) approved informed consent form

Who cannot join

  • Preexisting sensory neuropathy Grade ≥ 2
  • Preexisting motor neuropathy Grade ≥ 2
  • Uncontrolled central nervous system metastases
  • Use of any investigational drug within 14 days prior to the first dose of study drug
  • Any anticancer therapy within 14 days prior to the first dose of study drug, including: small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy, radiotherapy or any other agents to treat cancer (anti-hormonal therapy given as adjuvant therapy for early-stage estrogen receptor (ER) positive breast cancer is not considered cancer therapy for the purpose of this protocol)
  • Subjects with immunotherapy related adverse events requiring high doses of steroids (≥ 40 mg/day of prednisone) are not eligible.
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  • Any P-glycoprotein (P-gp) inducers/inhibitors or strong cytochrome P4503A (CYP3A) inhibitors within 14 days prior to the first dose of study drug
  • Thromboembolic events and/or bleeding disorders ≤ 14 days (e.g., deep vein thrombosis (DVT) or pulmonary embolism (PE)) prior to the first dose of study drug
  • Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms (including congestive heart failure) consistent with New York Heart Association Class III-IV within 6 months prior to the first dose of enfortumab vedotin.
  • Known Human Immunodeficiency Virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS)
  • Subjects with a positive Hepatitis B surface antigen and/or antihepatitis B core antibody. Subjects with a negative polymerase chain reaction (PCR) assay are permitted with appropriate antiviral prophylaxis.
  • Active Hepatitis C infection. Subjects who have been treated for Hepatitis C infection can be included if they have documented sustained virologic response of ≥ 12 weeks.
  • Decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy
  • Known sensitivity to any of the ingredients of the investigational product enfortumab vedotin (ASG-22CE)
  • Major surgery within 28 days prior to first dose of study drug
  • History of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Subjects with nonmelanoma skin cancer, localized prostate cancer treated with curative intent with no evidence of progression, low-risk or very low risk localized prostate cancer under active surveillance/watchful waiting without intent to treat, or carcinoma in situ of any time (if complete resection was performed) are allowed.
  • History of uncontrolled diabetes mellitus or diabetic neuropathy within 3 months of the first dose of study drug. Uncontrolled diabetes is defined as hemoglobin A1C (HbA1c) ≥ 8% or HbA1c > 7 to < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
  • Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of first dose of enfortumab vedotin. Routine antimicrobial prophylaxis is permitted.
  • Condition or situation which may put the subject at significant risk, may confound the study results, or may interfere significantly with subject's participation in the study
  • Any medical, psychiatric, addictive or other kind of disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures
  • Has ocular conditions such as:
  • Active infection or corneal ulcer (e.g. keratitis)
  • Monocularity
  • History of corneal transplantation
  • Contact lens dependent (if using contact lens, must be able to switch to glasses during the entire study duration)
  • Uncontrolled glaucoma (topical medications allowed)
  • Uncontrolled or evolving retinopathy, wet macular degeneration, uveitis, papilledema, or optic disc disorder

Trial locations and contacts

21 sites in 2 countries.

21 sites in 2 countries

United States18 sites

  • Site US00005

    Ann Arbor, Michigan, 48109

  • Site US00017

    Aurora, Colorado, 80045

  • Site US00023

    Chapel Hill, North Carolina, 27599

  • Site US00003

    Detroit, Michigan, 48201

  • Site US00024

    Fairfax, Virginia, 22031

  • Site US00004

    Fairway, Kansas, 66205

  • Site US00021

    Las Vegas, Nevada, 89119

  • Site US00012

    Los Angeles, California, 90033

  • Site US00009

    Madison, Wisconsin, 53792

  • Site US00007

    Miami, Florida, 33136

  • Site US00015

    Milwaukee, Wisconsin, 53226

  • Site US00006

    New Haven, Connecticut, 06520

  • Site US00018

    New York, New York, 10029

  • Site US00002

    New York, New York, 10065

  • Site US00013

    Philadelphia, Pennsylvania, 19111

  • Site US00020

    Pittsburgh, Pennsylvania, 15232

  • Site US00019

    Stanford, California, 94305

  • Site US00008

    Tampa, Florida, 33612

Other trials in United States

Canada3 sites

  • Site CA00011

    Calgary, Alberta, T2N 4N2

  • Site CA00001

    Edmonton, Alberta, T6G 1Z2

  • Site CA00010

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Phase 1 Study of the Safety and Pharmacokinetics of Escalating Doses of ASG-22CE Given as Monotherapy in Subjects With Metastatic Urothelial Cancer and Other Malignant Solid Tumors That Express Nectin-4

The purpose of this study is to evaluate the safety and pharmacokinetics of enfortumab vedotin as well as assess the immunogenicity and antitumor activity in subjects with metastatic urothelial cancer and other malignant solid tumors that express Nectin-4.

Read the detailed description

All subjects will receive a single 30 minute IV infusion of enfortumab vedotin once weekly for the first 3 weeks of every 4 weeks (i.e., on Days 1, 8, and 15). A cycle is 4 weeks.

This is a 3 part study. Part A will evaluate enfortumab vedotin in subjects with histologically confirmed malignant solid tumors (excluding sarcomas) that are resistant or have recurred. Subjects will continue treatment until disease progression, intolerability of enfortumab vedotin, investigator decision or consent withdrawal. Part A will follow a modified Continual Reassessment Method (mCRM).

Part B, will evaluate enfortumab vedotin in 3 different expansion cohorts: 1) Urothelial cancer subjects with renal insufficiency defined as a Creatinine Clearance ≥ 15 ml/min and < 30 ml/min, 2) subjects with Metastatic Non Small Cell Lung Cancer (NSCLC) and 3) subjects with Metastatic Ovarian Cancer. With the exception of the renal insufficiency cohort, enrollment into Part B will occur at the recommended phase 2 dose (RP2D) established in Part A. Enrollment into the renal insufficiency cohort will begin at starting dose and escalated using a 3 + 3 dose escalation design. Subjects will continue treatment until disease progression, intolerability of enfortumab vedotin or consent withdrawal.

Part C will evaluate enfortumab vedotin at the RP2D (determined from Part A) in subjects who have been previously treated with immune checkpoint inhibitors (CPI) in the metastatic setting. Subjects will continue treatment until disease progression, intolerability of enfortumab vedotin, investigator decision or consent withdrawal.

All subjects will be followed post-treatment through the 30-day Safety Follow-up Visit.

Being tested
enfortumab vedotin
Keywords
enfortumab vedotin, Metastatic Urothelial Cancer, Safety, AGS-22C3E, EV-101, Nectin 4 protein, humans, Clinical Trial, Phase 1, ASG-22CE, ASG-22ME, Pharmacokinetics of ASG-22CE

What participants receive

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

  • enfortumab vedotinDrug

    Also called ASP7465, ASG-22CE, ASG-22ME

    intravenous (IV) infusion

Study groups in NCT02091999
Study groupRoleWhat they receive
Part A enfortumab vedotin Dose Escalation (Dose Levels 1-4)ExperimentalAll subjects will receive a single 30 minute intravenous (IV) infusion of enfortumab vedotin once weekly for the first 3 weeks of every 4 week cycle (i.e., on Days 1, 8 and 15).
Receives: Drug: enfortumab vedotin
Part B enfortumab vedotin Renal Insufficiency ExpansionExperimentalSubjects will receive a single 30 minute IV infusion of enfortumab vedotin at a dose level below and escalated up to the preliminary RP2D once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8 and 15) until disease progression, intolerability of the investigational product or consent withdrawal. A cycle is 4 weeks.
Receives: Drug: enfortumab vedotin
Part B enfortumab vedotin NSCLC ExpansionExperimentalSubjects will receive a single 30 minute IV infusion of enfortumab vedotin at the preliminary RP2D once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8 and 15) until disease progression, intolerability of the investigational product or consent withdrawal. A cycle is 4 weeks.
Receives: Drug: enfortumab vedotin
Part B enfortumab vedotin Ovarian Cancer ExpansionExperimentalSubjects will receive a single 30 minute IV infusion of enfortumab vedotin at the preliminary RP2D once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8 and 15) until disease progression, intolerability of the investigational product or consent withdrawal. A cycle is 4 weeks.
Receives: Drug: enfortumab vedotin
Part C enfortumab vedotin CPI Treated ExpansionExperimentalSubjects will receive a single 30 minute IV infusion of enfortumab vedotin at the preliminary RP2D once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8 and 15). A cycle is 4 weeks. Subjects will continue treatment until disease progression, intolerability of enfortumab vedotin, Investigator decision or consent withdrawal.
Receives: Drug: enfortumab vedotin

What is being measured

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

  1. Incidence of adverse events

    Measured: up to 36 months

  2. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Concentration at the end of infusion (CEOI)

    Measured: Days 1-4, 8, 15-18 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 months

  3. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Maximum observed concentration (Cmax)

    Measured: Days 1-4, 8, 15-18 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 months

  4. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Trough concentration (Ctrough)

    Measured: Days 1-4, 8, 15-18 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 months

  5. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Time to maximum concentration (Tmax)

    Measured: Days 1-4, 8, 15-18 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 months

  6. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-7)

    Measured: Days 1-4, 8, 15-18 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 months

  7. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Terminal or apparent terminal half-life (t1/2)

    Measured: Days 1-4, 8, 15-18 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 months

  8. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Systemic clearance (CL)

    Measured: Days 1-4, 8, 15-18 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 months

  9. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Volume of distribution at steady state (Vss)

    Measured: Days 1-4, 8, 15-18 of Cycle 1 and Days 1, 8, and 15 of Cycle 2 and Day 1 of subsequent cycles up to an average of 24 months

Secondary outcomes (7)

  1. Incidence of Anti-Drug Antibody (ADA)

    Measured: up to 24 months

  2. Tumor response

    Incidence of tumor response defined as either a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.1) that is confirmed ≥ 28 days later

    Measured: up to 24 months

  3. Objective response rate

    Defined as the percentage of subjects who experience a best response of either CR or PR in that cohort. CR and PR must be confirmed ≥ 28 days later.

    Measured: up to 24 months

  4. Disease control rate

    Defined as the percentage of subjects who experience a best response of CR, PR or stable disease (SD)

    Measured: up to 24 months

  5. Progression Free Survival (PFS)

    Time from the date of first infusion to the earliest date of documented disease progression per radiological evidence or death from any cause

    Measured: 36 months

  6. Overall Survival

    Time from the date of first infusion until the date of death from any cause.

    Measured: 36 months

  7. Duration of Response

    Time from the date of the first response complete response (CRC) or partial response (PR) to the earliest date of disease progression or death from any cause. DOR is only defined for subjects who have best overall response of CR or PR

    Measured: 36 months

Timeline

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

  1. First posted19 Mar 2014 (estimated)
  2. Study start14 May 2014
  3. Primary completion7 Dec 2022
  4. Study completion7 Dec 2022

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
213 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02091999
Sponsor's protocol ID
ASG-22CE-13-2
Status last verified
Jul 2026
First submitted
18 Mar 2014
Last updated
17 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/
Expanded access
Available

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing enfortumab vedotin in people with Metastatic Urothelial Cancer and Other Malignant Solid Tumors, run by Astellas Pharma Global Development, Inc. at 21 sites in 2 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 23 inclusion and 27 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: finished, as of the sponsor's last update on 17 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States, Canada. 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 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.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence of adverse events (time frame: up to 36 months). The study lists 9 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 NCT02091999.

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 17 Jul 2026; AzTrials last refreshed its copy on 26 Oct 2026.

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