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BRIEF TITLE: Enfortumab Vedotin (ASG-22CE) as Monotherapy or in Combination With Other Anticancer Therapies for the Treatment of 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: MK-3475-869,KEYNOTE KN-869
  • NCT ID: NCT03288545
  • NCT Alias:
  • Sponsor: Astellas Pharma Global Development, Inc. - Industry
  • Source: Astellas Pharma Inc

Description

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.

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 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.

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

Overal Status Start Date Phase Study Type
Recruiting October 11, 2017 Phase 1/Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Type, incidence, severity, seriousness, and relatedness of adverse events (Dose escalation and Expansion Parts 1 to 3; non-randomized 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 (Dose escalation and Expansion Parts 1 to 3; non-randomized 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 central pathology review (MIBC coohorts only)

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

Primary Outcome 4 - Measure: 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)

Primary Outcome 4 - Time Frame: Up to 3 years

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 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.

- 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.

- 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 radical cystectomy and pelvic lymph node
dissection.

Exclusion Criteria:

- 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).

- 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.

- Evidence of nodal or metastatic disease on imaging per local assessment.
Participants in Cohort L with pT1 disease may not have ≥N2 nodal disease on
imaging.

- 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: Seagen Inc.

Overall Contact

Name: Seagen, Inc. Trial Information Support

Phone: 866-333-7436

Email: clinicaltrials@seagen.com

Locations

Facility Status Contact
Alaska Urological Institute
Anchorage, Alaska 99503
United States
Completed
Banner MD Anderson Cancer Center
Gilbert, Arizona 85234
United States
Recruiting
Mayo Clinic Arizona
Phoenix, Arizona 85054
United States
Recruiting
Arizona Oncology Associates, PC - HOPE
Tucson, Arizona 85710
United States
Recruiting
Highlands Oncology Group
Fayetteville, Arkansas 72703
United States
Recruiting
Tower Hematology Oncology Medical Group
Beverly Hills, California 90211
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, Davis Comprehensive Cancer Center
Sacramento, California 95817
United States
Recruiting
University of California at San Francisco
San Francisco, California 94134
United States
Recruiting
Saint Joseph Heritage Medical Group
Santa Rosa, California 95403
United States
Recruiting
Stanford Cancer Center / Blood & Marrow Transplant Program
Stanford, California 94305
United States
Recruiting
Kaiser Permanente Southern California
Woodland Hills, California 91367
United States
Recruiting
Rocky Mountain Cancer Centers - Aurora
Aurora, Colorado 80012
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
Eastern CT Hematology and Oncology Associates
Norwich, Connecticut 06360
United States
Recruiting
Georgetown University Medical Center
Washington, District of Columbia 20007
United States
Recruiting
Boca Raton Regional Hospital / Lynn Cancer Institute
Boca Raton, Florida 33486
United States
Recruiting
Holy Cross Hospital - Michael and Dianne Bienes Comprehensive Cancer Center
Fort Lauderdale, Florida 33308
United States
Recruiting
Mayo Clinic Florida
Jacksonville, Florida 32224
United States
Recruiting
University of Miami
Miami, Florida 33136
United States
Recruiting
Piedmont Cancer Institute
Atlanta, Georgia 30309
United States
Recruiting
Winship Cancer Institute / Emory University School of Medicine
Atlanta, Georgia 30322
United States
Recruiting
University of Chicago Medical Center
Chicago, Illinois 60637-1470
United States
Recruiting
Decatur Memorial Hospital - Illinois
Decatur, Illinois 62526
United States
Recruiting
Northwestern Medicine Cancer Center - Kishwaukee / Kishwaukee Cancer Center
DeKalb, Illinois 60115
United States
Recruiting
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois 60134
United States
Recruiting
Cardinal Bernardin Cancer Center / Loyola University Medical Center
Maywood, Illinois 60153
United States
Recruiting
Northwestern Medicine Cancer Center - Warrenville / Central DuPage Hospital - Cancer Care
Warrenville, Illinois 60555
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
Ochsner Clinic Foundation
New Orleans, Louisiana 70121
United States
Recruiting
Southcoast Centers for Cancer Care - Fairhaven Site
Fairhaven, Massachusetts 02719
United States
Recruiting
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan 48109
United States
Recruiting
Henry Ford Health System
Detroit, Michigan 48202
United States
Recruiting
McLaren Greater Lansing Hospital
Lansing, Michigan 48910
United States
Recruiting
University of Minnesota
Minneapolis, Minnesota 55455
United States
Recruiting
University of Mississippi Medical Center
Jackson, Mississippi 39213
United States
Recruiting
Washington University School of Medicine - Siteman Cancer Center
Saint Louis, Missouri 63110
United States
Recruiting
Nebraska Hematology Oncology P.C.
Lincoln, Nebraska 68506
United States
Recruiting
OptumCare Cancer Center
Las Vegas, Nevada 89102
United States
Recruiting
Memorial Sloan Kettering Cancer Center - Basking Ridge
Basking Ridge, New Jersey 07920
United States
Recruiting
Hackensack University Medical Center
Hackensack, New Jersey 07601
United States
Recruiting
Memorial Sloan Kettering Cancer Center - Monmouth
Middletown, New Jersey 07748
United States
Recruiting
Memorial Sloan Kettering Cancer Center - Bergen
Montvale, New Jersey 07645
United States
Recruiting
University of New Mexico Cancer Center
Albuquerque, New Mexico 87106
United States
Recruiting
New York Oncology Hematology, P.C.
Albany, New York 12206
United States
Recruiting
Roswell Park Cancer Institute
Buffalo, New York 14263
United States
Recruiting
Memorial Sloan Kettering Cancer Center - Commack
Commack, New York 11725
United States
Recruiting
Memorial Sloan Kettering Cancer Center - Westchester
Harrison, New York 10604
United States
Recruiting
Northwell Cancer Center / Monter Cancer Center
Lake Success, New York 11042
United States
Recruiting
NYU Winthrop Hospital
Mineola, New York 11501
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
University of Rochester Medical Center
Rochester, New York 14642
United States
Recruiting
Memorial Sloan Kettering Cancer Center - Nassau
Uniondale, New York 11553
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
Vidant Medical Center
Greenville, North Carolina 27834
United States
Recruiting
Gabrail Cancer Center Research, LLC
Canton, Ohio 44718
United States
Recruiting
Case Western Reserve University / University Hospitals Case Medical Center
Cleveland, Ohio 44106
United States
Recruiting
Toledo Clinic Cancer Center
Toledo, Ohio 43623
United States
Recruiting
CMOH Broomall
Broomall, Pennsylvania 19008
United States
Recruiting
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania 17033
United States
Recruiting
Fox Chase Cancer Center
Philadelphia, Pennsylvania 19111
United States
Recruiting
Allegheny General Hospital
Pittsburgh, Pennsylvania 15212
United States
Recruiting
Medical University of South Carolina/Hollings Cancer Center
Charleston, South Carolina 29425
United States
Recruiting
Saint Francis Hospital Cancer Center
Greenville, South Carolina 29607
United States
Recruiting
Carolina Urologic Research Center
Myrtle Beach, South Carolina 29572
United States
Recruiting
Sarah Cannon Research Institute
Chattanooga, Tennessee 37404
United States
Recruiting
Tennessee Oncology / Sarah Cannon Research Institute
Nashville, Tennessee 37203
United States
Completed
Texas Oncology - Fort Worth Cancer Center
Fort Worth, Texas 76104
United States
Recruiting
University of Texas Health Science Center at San Antonio
San Antonio, Texas 78229
United States
Recruiting
Texas Oncology - Tyler
Tyler, Texas 75702
United States
Recruiting
Utah Cancer Specialists
Salt Lake City, Utah 84106
United States
Recruiting
University of Virginia
Charlottesville, Virginia 22903
United States
Recruiting
Medical Oncology Associates
Spokane, Washington 99208
United States
Recruiting
Medical College of Wisconsin (Milwaukee)
Milwaukee, Wisconsin 53226
United States
Recruiting
Site CA11011
Kingston, Ontario K7L 2V7
Canada
Recruiting
Site CA11005
Montreal, Quebec H3T1E2
Canada
Recruiting
Site CA11002
Sherbrooke, Quebec J1H 5N4
Canada
Recruiting