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BRIEF TITLE: 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

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


  • Org Study ID: SGN22E-002
  • Secondary ID:
  • NCT ID: NCT03288545
  • NCT Alias:
  • Sponsor: Astellas Pharma Global Development, Inc. - Industry
  • Source: Astellas Pharma Inc

Brief 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). This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra. Some parts of the study will look at locally-advanced and metastatic urothelial cancer, 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 urothelial cancer, 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.

Detailed Description


This study will examine the safety and anticancer activity of enfortumab vedotin given
intravenously as monotherapy and in combination with other anticancer therapies to 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: dose escalation
(enfortumab vedotin + pembrolizumab) and dose expansion (cohorts of enfortumab vedotin +
pembrolizumab and/or chemotherapy) for locally advanced and metastatic urothelial cancer, and
enfortumab alone and combination with pembrolizumab in patients with earlier stage of the
disease (muscle invasive urothelial cancer).

Overal Status Start Date Phase Study Type
Recruiting October 11, 2017 Phase 1 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Type, incidence, severity, seriousness, and relatedness of adverse events (locally advanced/metastatic urothelial cancer [la/mUC] cohorts only)

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

Primary Outcome 2 - Measure: Type, incidence, and severity of laboratory abnormalities (la/mUC cohorts only)

Primary Outcome 2 - Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated.

Primary Outcome 3 - Measure: Pathological complete response (pCR) rate per local pathology review (muscle invasive urothelial cancer [MIUC] cohorts only)

Primary Outcome 3 - Time Frame: Up to approximately 5 months

Condition:

  • Carcinoma, Transitional Cell
  • Urinary Bladder Neoplasms
  • Urologic Neoplasms
  • Renal Pelvis Neoplasms
  • Urothelial Cancer
  • Ureteral Neoplasms
  • Urethral Neoplasms

Eligibility

Criteria:
Inclusion Criteria:

- Locally advanced or metastatic urothelial (la/mUC) - Cohorts A, B, D, E, F, and G

- 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.

- Eligible for pembrolizumab (Dose-escalation cohorts, Cohorts A, B, and G).

- 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.

- 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.

- Muscle Invasive Urothelial Cancer (MIUC) - Cohorts H and J

- Histologically confirmed muscle invasive urothelial cancer of the bladder at
clinical stage cT2-T4a.

- Medically fit (i.e. eligible for surgery) and scheduled for radical cystectomy.

- ECOG performance status of 0, 1, or 2.

- Cohort H and J: Ineligible for cisplatin-based chemotherapy and no prior systemic
treatment, chemoradiation, or radiation therapy for MIUC. May have received prior
intravesical Bacillus Calmette-Guerin (BCG) or intravesical chemotherapy for
non-muscle invasive urothelial cancer.

- Cohort J: Eligible for pembrolizumab.

Exclusion Criteria:

- la/mUC - Cohorts A, B, D, E, F, and G

- 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).

- 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.

- MIUC - Cohorts H and J

- Received prior systemic treatment, chemoradiation, and/or radiation therapy of
muscle invasive urothelial 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.

- Evidence of measurable nodal or metastatic disease.

- 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.

- History of another malignancy within 3 years before first dose of study drug.
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Anne-Sophie Carret, MD

Role: Study Director

Affiliation: Seattle Genetics, Inc.

Overall Contact

Name: Seattle Genetics Trial Information Support

Phone: 866-333-7436

Email: clinicaltrials@seagen.com

Locations

Facility Status Contact
Alaska Urological Institute
Anchorage, Alaska 99503
United States
Recruiting
Banner MD Anderson Cancer Center
Gilbert, Arizona 85234
United States
Recruiting
Highlands Oncology Group
Fayetteville, Arkansas 72703
United States
Recruiting
UC San Diego / Moores Cancer Center
La Jolla, California 92093
United States
Recruiting
University of California Irvine - Newport
Orange, California 92868
United States
Recruiting
University of California at San Francisco
San Francisco, California 94134
United States
Recruiting
Stanford Cancer Center / Blood & Marrow Transplant Program
Stanford, California 94305
United States
Recruiting
University of Colorado Hospital / University of Colorado
Aurora, Colorado 80045-0510
United States
Recruiting
Yale Cancer Center
New Haven, Connecticut 06520
United States
Recruiting
University of Miami
Miami, Florida 33136
United States
Recruiting
Winship Cancer Institute / Emory University School of Medicine
Atlanta, Georgia 30322
United States
Recruiting
Decatur Memorial Hospital - Illinois
Decatur, Illinois 62526
United States
Recruiting
Cardinal Bernardin Cancer Center / Loyola University Medical Center
Maywood, Illinois 60153
United States
Recruiting
University of Kansas Cancer Center
Westwood, Kansas 66205
United States
Recruiting
Tulane University Hospital and Clinic
New Orleans, Louisiana 70112
United States
Recruiting
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan 48109
United States
Recruiting
University of Minnesota
Minneapolis, Minnesota 55455
United States
Recruiting
Hackensack University Medical Center
Hackensack, New Jersey 07601
United States
Recruiting
Roswell Park Cancer Institute
Buffalo, New York 14263
United States
Recruiting
New York University (NYU) Cancer Institute
New York, New York 10016
United States
Recruiting
Weill Cornell Medical College
New York, New York 10065
United States
Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York 10087-9049
United States
Recruiting
UNC Lineberger Comprehensive Cancer Center / University of North Carolina
Chapel Hill, North Carolina 27599
United States
Recruiting
Levine Cancer Institute
Charlotte, North Carolina 28204
United States
Recruiting
Case Western Reserve University / University Hospitals Case Medical Center
Cleveland, Ohio 44106
United States
Recruiting
Medical University of South Carolina/Hollings Cancer Center
Charleston, South Carolina 29425
United States
Recruiting
Medical College of Wisconsin (Milwaukee)
Milwaukee, Wisconsin 53226
United States
Recruiting