ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 3 of 13 for:    Recruiting, Not yet recruiting, Available Studies | "Urethral Neoplasms"

A Safety Study of Enfortumab Vedotin Plus Immune Checkpoint Inhibitor Therapy for Patients With Urothelial Bladder Cancer (EV-103)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03288545
Recruitment Status : Recruiting
First Posted : September 20, 2017
Last Update Posted : May 24, 2018
Sponsor:
Collaborator:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Brief Summary:

This is a study that will test how an experimental drug (enfortumab vedotin) combined with a kind of anticancer drug called an immune checkpoint inhibitor (CPI) affects patients with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra that has spread to nearby tissues or to other areas of the body.

Patients will get the drugs twice every 21-day cycle. Patients will get enfortumab vedotin plus the CPI on day 1. Patients will get enfortumab vedotin only on day 8.

This study will look at the side effects of giving the two drugs with each other. 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 treatment.


Condition or disease Intervention/treatment Phase
Carcinoma, Transitional Cell Urinary Bladder Neoplasms Urologic Neoplasms Renal Pelvis Neoplasms Urothelial Cancer Ureteral Neoplasms Urethral Neoplasms Drug: enfortumab vedotin Drug: pembrolizumab Drug: atezolizumab Phase 1

Detailed Description:

This study will examine the safety and anticancer activity of enfortumab vedotin given intravenously in combination with CPI therapy to patients with locally advanced or metastatic urothelial cancer. The primary goal of the study is to determine the safety and tolerability of enfortumab vedotin in combination with CPI therapy.

The study will be conducted in 2 parts: dose escalation (enfortumab vedotin + pembrolizumab) and dose expansion (cohorts of enfortumab vedotin + CPI [either pembrolizumab or atezolizumab]).


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 85 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: single-arm, open-label, multicenter study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Dose-escalation and Dose-expansion Study of Enfortumab Vedotin (ASG-22CE) in Combination With Immune Checkpoint Inhibitor (CPI) Therapy for Treatment of Patients With Locally Advanced or Metastatic Urothelial Cancer
Actual Study Start Date : October 11, 2017
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Enfortumab Vedotin + CPI
Enfortumab vedotin on days 1 and 8 plus CPI therapy (either pembrolizumab or atezolizumab) on day 1 every 21 days
Drug: enfortumab vedotin
Intravenous (IV) infusion on days 1 and 8 every 21 days
Other Names:
  • ASG-22CE
  • ASG-22ME

Drug: pembrolizumab
IV infusion on day 1 every 21 days
Other Name: Keytruda

Drug: atezolizumab
IV infusion on day 1 every 21 days
Other Name: Tecentriq




Primary Outcome Measures :
  1. Incidence of dose-limiting toxicity (DLT) [ Time Frame: 21 days ]
    Incidence of DLTs that are considered related to enfortumab vedotin and/or enfortumab vedotin + CPI, and are not attributed to CPI alone

  2. Type, incidence, severity, seriousness, and relatedness of adverse events [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 22 months ]
    Descriptive statistics will be used to summarize results

  3. Type, incidence, and severity of laboratory abnormalities [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 22 months ]
    Descriptive statistics will be used to summarize results


Secondary Outcome Measures :
  1. Objective response rate (ORR) by investigator assessment according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) [ Time Frame: Up to 34 months ]
    The proportion of patients with confirmed complete response (CR) or partial response (PR) according to RECIST 1.1

  2. Disease control rate (DCR) by investigator assessment according to RECIST 1.1 [ Time Frame: Up to 34 months ]
    Proportion of patients with CR, PR, or stable disease (SD) according to RECIST 1.1

  3. Duration of response (DOR) by investigator assessment according to RECIST 1.1 [ Time Frame: Up to 34 months ]
    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

  4. Progression free survival (PFS) by investigator assessment according to RECIST 1.1 [ Time Frame: Up to 34 months ]
    The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first

  5. Overall survival (OS) [ Time Frame: Up to 34 months ]
    The time from start of study treatment to date of death due to any cause

  6. Pharmacokinetics (PK) parameter for enfortumab vedotin: Maximum concentration (Cmax) [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    Cmax will be derived from the PK blood samples collected

  7. PK parameter for monomethyl auristatin E (MMAE): Cmax [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    Cmax will be derived from the PK blood samples collected

  8. PK parameter for enfortumab vedotin: Time to maximum concentration (Tmax) [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    Tmax will be derived from the PK blood samples collected

  9. PK parameter for MMAE: Tmax [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    Tmax will be derived from the PK blood samples collected

  10. PK parameter for enfortumab vedotin: Area under the concentration-time curve (AUC) [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    AUC will be derived from the PK blood samples collected

  11. PK parameter for MMAE: AUC [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    AUC will be derived from the PK blood samples collected

  12. PK parameter for enfortumab vedotin: Half-life (t1/2) [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    t1/2 will be derived from the PK blood samples collected

  13. PK parameter for MMAE: t1/2 [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    t1/2 will be derived from the PK blood samples collected

  14. Incidence of antitherapeutic antibodies (ATA) to enfortumab vedotin [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 22 months ]
    Blood samples for ATA analysis will be collected



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically documented transitional cell carcinoma of the urothelium (squamous differentiation or mixed cell types allowed).
  • Locally advanced disease that is not resectable or metastatic disease.
  • Eligible to receive treatment with a CPI.
  • Either ineligible for first-line cisplatin-based chemotherapy or have disease progression during or following treatment with at least one platinum-containing regimen.
  • An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2.

Exclusion Criteria:

  • Received any prior treatment with a CPI.
  • Received any prior treatment with CD137 agonists or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors.
  • 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).
  • Patients with conditions requiring high doses of steroids or other immunosuppressive medications are excluded.
  • Prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03288545


Contacts
Contact: Seattle Genetics Trial Information Support 866-333-7436 clinicaltrials@seagen.com

Locations
United States, California
Stanford Cancer Center / Blood & Marrow Transplant Program Recruiting
Stanford, California, United States, 94305
United States, Colorado
University of Colorado Hospital / University of Colorado Recruiting
Aurora, Colorado, United States, 80045-0510
United States, Connecticut
Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06520
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
United States, Georgia
Winship Cancer Institute / Emory University School of Medicine Recruiting
Atlanta, Georgia, United States, 30322
United States, Kansas
University of Kansas Cancer Center Recruiting
Westwood, Kansas, United States, 66205
United States, Michigan
University of Michigan Comprehensive Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Weill Cornell Medical College Recruiting
New York, New York, United States, 10065
United States, North Carolina
UNC Lineberger Comprehensive Cancer Center / University of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27599
Levine Cancer Institute Recruiting
Charlotte, North Carolina, United States, 28204
United States, Ohio
Case Western Reserve University / University Hospitals Case Medical Center Recruiting
Cleveland, Ohio, United States, 44106
United States, South Carolina
Medical University of South Carolina/Hollings Cancer Center Recruiting
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Seattle Genetics, Inc.
Investigators
Study Director: Anne-Sophie Carret, MD Seattle Genetics, Inc.

Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT03288545     History of Changes
Other Study ID Numbers: SGN22E-002
First Posted: September 20, 2017    Key Record Dates
Last Update Posted: May 24, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
ASG-22ME
ASG-22CE
Antibody-drug conjugate
Antineoplastic agents
CPI
Enfortumab vedotin
Locally advanced urothelial cancer
Drug therapy
Metastatic urothelial cancer
Nectin-4
Atezolizumab
Checkpoint Inhibitors
Pembrolizumab

Additional relevant MeSH terms:
Urethral Neoplasms
Neoplasms
Urinary Bladder Neoplasms
Urologic Neoplasms
Carcinoma, Transitional Cell
Ureteral Neoplasms
Pelvic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Ureteral Diseases
Urethral Diseases
Pembrolizumab
Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs