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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 Dose-escalation and Dose-expansion Study of Enfortumab Vedotin (ASG-22CE) in Combination With Pembrolizumab and/or Chemotherapy for Treatment of Patients With Locally Advanced or Metastatic 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) with different combinations of pembrolizumab and/or chemotherapy. 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 that has spread to nearby tissues or to other areas of the body. This study will have different parts to look at the side effects of (1) enfortumab vedotin with pembrolizumab, (2) enfortumab vedotin with chemotherapy, and (3) enfortumab vedotin with pembrolizumab and chemotherapy. 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 in combination with pembrolizumab and/or chemotherapy 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 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).

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

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

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

Condition:

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

Eligibility

Criteria:
Inclusion Criteria:

- Histologically documented locally advanced or metastatic urothelial carcinoma
(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.

Exclusion Criteria:

- 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
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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
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
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
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
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