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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

INTRODUCTION

  • Org Study ID: SGN22E-002
  • Secondary ID: MK-3475-869, KEYNOTE KN-869
  • NTC ID: NCT03288545
  • Sponsor: Astellas Pharma Global Development, 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. For more information about this trial, please click here.

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 or metastatic urothelial cancer (la/mUC), 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

  • Overall Status
    Recruiting
  • Start Date
    October 11, 2017
  • Phase
    Phase 1, Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Type, incidence, severity, seriousness, and relatedness of adverse events (Dose escalation and Expansion Parts 1 to 3 cohorts only)

Primary Outcome 1 - Timeframe: 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 cohorts only)

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

Primary Outcome 3 - 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 3 - Timeframe: Up to 3 years

Primary Outcome 4 - Measure: Pathological complete response (pCR) rate per central pathology review (MIBC cohorts only)

Primary Outcome 4 - Timeframe: Up to approximately 5 months

CONDITION

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

ELIGIBILITY

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. Urothelial tumors not originating in the bladder (eg, upper tract tumors, urethral tumors) are ineligible.

- 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 RC+PLND.
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.

- For participants in Cohort H, evidence of nodal disease on imaging. For participants in Cohort L, ≥N2 nodal disease on imaging.

- Participant has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC.

- 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.

- Participants with a history of another invasive malignancy within 3 years before first dose of study drug.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Anne-Sophie Carret, MD, Sujata Narayanan, MD

Role: Study Director, Study Director

Affiliation: Seagen Inc., Seagen Inc.

Overall Contact

Name: Anne-Sophie Carret, MD, Sujata Narayanan, MD

Phone: 866-333-7436

Email: clinicaltrials@seagen.com

LOCATION

Facility Status Contact
Facility: Banner MD Anderson Cancer Center
Gilbert, Arizona 85234
United States
Status: Recruiting Contact: N/A
Facility: Mayo Clinic Arizona
Phoenix, Arizona 85054
United States
Status: Recruiting Contact: N/A
Facility: Arizona Oncology Associates, PC - HOPE
Tucson, Arizona 85710
United States
Status: Recruiting Contact: N/A
Facility: Highlands Oncology Group
Fayetteville, Arkansas 72703
United States
Status: Recruiting Contact: N/A
Facility: Tower Hematology Oncology Medical Group
Beverly Hills, California 90211
United States
Status: Recruiting Contact: N/A
Facility: UC San Diego / Moores Cancer Center
La Jolla, California 92093
United States
Status: Recruiting Contact: N/A
Facility: University of California Irvine - Newport
Orange, California 92868
United States
Status: Recruiting Contact: N/A
Facility: University of California, Davis Comprehensive Cancer Center
Sacramento, California 95817
United States
Status: Recruiting Contact: N/A
Facility: University of California at San Francisco
San Francisco, California 94134
United States
Status: Recruiting Contact: N/A
Facility: Saint Joseph Heritage Medical Group
Santa Rosa, California 95403
United States
Status: Recruiting Contact: N/A
Facility: Stanford Cancer Center / Blood & Marrow Transplant Program
Stanford, California 94305
United States
Status: Recruiting Contact: N/A
Facility: Kaiser Permanente Southern California
Woodland Hills, California 91367
United States
Status: Recruiting Contact: N/A
Facility: Rocky Mountain Cancer Centers - Aurora
Aurora, Colorado 80012
United States
Status: Recruiting Contact: N/A
Facility: University of Colorado Hospital / University of Colorado
Aurora, Colorado 80045-0510
United States
Status: Recruiting Contact: N/A
Facility: Yale Cancer Center
New Haven, Connecticut 06520
United States
Status: Recruiting Contact: N/A
Facility: Eastern CT Hematology and Oncology Associates
Norwich, Connecticut 06360
United States
Status: Recruiting Contact: N/A
Facility: Georgetown University Medical Center
Washington, District of Columbia 20007
United States
Status: Recruiting Contact: N/A
Facility: Boca Raton Regional Hospital / Lynn Cancer Institute
Boca Raton, Florida 33486
United States
Status: Recruiting Contact: N/A
Facility: Holy Cross Hospital - Michael and Dianne Bienes Comprehensive Cancer Center
Fort Lauderdale, Florida 33308
United States
Status: Recruiting Contact: N/A
Facility: Mayo Clinic Florida
Jacksonville, Florida 32224
United States
Status: Recruiting Contact: N/A
Facility: University of Miami
Miami, Florida 33136
United States
Status: Recruiting Contact: N/A
Facility: Piedmont Cancer Institute
Atlanta, Georgia 30309
United States
Status: Recruiting Contact: N/A
Facility: Winship Cancer Institute / Emory University School of Medicine
Atlanta, Georgia 30322
United States
Status: Recruiting Contact: N/A
Facility: University of Chicago Medical Center
Chicago, Illinois 60637-1470
United States
Status: Recruiting Contact: N/A
Facility: Decatur Memorial Hospital - Illinois
Decatur, Illinois 62526
United States
Status: Recruiting Contact: N/A
Facility: Northwestern Medicine Cancer Center - Kishwaukee / Kishwaukee Cancer Center
DeKalb, Illinois 60115
United States
Status: Recruiting Contact: N/A
Facility: Northwestern Medicine Cancer Center Delnor
Geneva, Illinois 60134
United States
Status: Recruiting Contact: N/A
Facility: Cardinal Bernardin Cancer Center / Loyola University Medical Center
Maywood, Illinois 60153
United States
Status: Recruiting Contact: N/A
Facility: Northwestern Medicine Cancer Center - Warrenville / Central DuPage Hospital - Cancer Care
Warrenville, Illinois 60555
United States
Status: Recruiting Contact: N/A
Facility: University of Kansas Cancer Center
Westwood, Kansas 66205
United States
Status: Recruiting Contact: N/A
Facility: Tulane University Hospital and Clinic
New Orleans, Louisiana 70112
United States
Status: Recruiting Contact: N/A
Facility: Ochsner Clinic Foundation
New Orleans, Louisiana 70121
United States
Status: Recruiting Contact: N/A
Facility: Maryland Oncology Hematology, P.A.
Silver Spring, Maryland 20904
United States
Status: Recruiting Contact: N/A
Facility: Southcoast Centers for Cancer Care - Fairhaven Site
Fairhaven, Massachusetts 02719
United States
Status: Recruiting Contact: N/A
Facility: University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan 48109
United States
Status: Recruiting Contact: N/A
Facility: Henry Ford Health System
Detroit, Michigan 48202
United States
Status: Recruiting Contact: N/A
Facility: McLaren Greater Lansing Hospital
Lansing, Michigan 48910
United States
Status: Recruiting Contact: N/A
Facility: University of Minnesota
Minneapolis, Minnesota 55455
United States
Status: Recruiting Contact: N/A
Facility: University of Mississippi Medical Center
Jackson, Mississippi 39213
United States
Status: Recruiting Contact: N/A
Facility: Washington University School of Medicine - Siteman Cancer Center
Saint Louis, Missouri 63110
United States
Status: Recruiting Contact: N/A
Facility: Nebraska Hematology Oncology P.C.
Lincoln, Nebraska 68506
United States
Status: Recruiting Contact: N/A
Facility: OptumCare Cancer Center
Las Vegas, Nevada 89102
United States
Status: Recruiting Contact: N/A
Facility: Memorial Sloan Kettering Cancer Center - Basking Ridge
Basking Ridge, New Jersey 07920
United States
Status: Recruiting Contact: N/A
Facility: Hackensack University Medical Center
Hackensack, New Jersey 07601
United States
Status: Recruiting Contact: N/A
Facility: Memorial Sloan Kettering Cancer Center - Monmouth
Middletown, New Jersey 07748
United States
Status: Recruiting Contact: N/A
Facility: Memorial Sloan Kettering Cancer Center - Bergen
Montvale, New Jersey 07645
United States
Status: Recruiting Contact: N/A
Facility: University of New Mexico Cancer Center
Albuquerque, New Mexico 87106
United States
Status: Recruiting Contact: N/A
Facility: New York Oncology Hematology, P.C.
Albany, New York 12206
United States
Status: Recruiting Contact: N/A
Facility: Roswell Park Cancer Institute
Buffalo, New York 14263
United States
Status: Recruiting Contact: N/A
Facility: Memorial Sloan Kettering Cancer Center - Commack
Commack, New York 11725
United States
Status: Recruiting Contact: N/A
Facility: Memorial Sloan Kettering Cancer Center - Westchester
Harrison, New York 10604
United States
Status: Recruiting Contact: N/A
Facility: Northwell Cancer Center / Monter Cancer Center
Lake Success, New York 11042
United States
Status: Recruiting Contact: N/A
Facility: NYU Winthrop Hospital
Mineola, New York 11501
United States
Status: Recruiting Contact: N/A
Facility: New York University (NYU) Cancer Institute
New York, New York 10016
United States
Status: Recruiting Contact: N/A
Facility: Weill Cornell Medical College
New York, New York 10065
United States
Status: Recruiting Contact: N/A
Facility: Memorial Sloan Kettering Cancer Center
New York, New York 10087-9049
United States
Status: Recruiting Contact: N/A
Facility: University of Rochester Medical Center
Rochester, New York 14642
United States
Status: Recruiting Contact: N/A
Facility: Memorial Sloan Kettering Cancer Center - Nassau
Uniondale, New York 11553
United States
Status: Recruiting Contact: N/A
Facility: UNC Lineberger Comprehensive Cancer Center / University of North Carolina
Chapel Hill, North Carolina 27599
United States
Status: Recruiting Contact: N/A
Facility: Levine Cancer Institute
Charlotte, North Carolina 28204
United States
Status: Recruiting Contact: N/A
Facility: Duke University Medical Center
Durham, North Carolina 27710
United States
Status: Recruiting Contact: N/A
Facility: Vidant Medical Center
Greenville, North Carolina 27834
United States
Status: Recruiting Contact: N/A
Facility: Gabrail Cancer Center Research, LLC
Canton, Ohio 44718
United States
Status: Recruiting Contact: N/A
Facility: Case Western Reserve University / University Hospitals Case Medical Center
Cleveland, Ohio 44106
United States
Status: Recruiting Contact: N/A
Facility: Toledo Clinic Cancer Center
Toledo, Ohio 43623
United States
Status: Recruiting Contact: N/A
Facility: CMOH Broomall
Broomall, Pennsylvania 19008
United States
Status: Recruiting Contact: N/A
Facility: Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania 17033
United States
Status: Recruiting Contact: N/A
Facility: Fox Chase Cancer Center
Philadelphia, Pennsylvania 19111
United States
Status: Recruiting Contact: N/A
Facility: Allegheny General Hospital
Pittsburgh, Pennsylvania 15212
United States
Status: Recruiting Contact: N/A
Facility: Medical University of South Carolina/Hollings Cancer Center
Charleston, South Carolina 29425
United States
Status: Recruiting Contact: N/A
Facility: Saint Francis Hospital Cancer Center
Greenville, South Carolina 29607
United States
Status: Recruiting Contact: N/A
Facility: Carolina Urologic Research Center
Myrtle Beach, South Carolina 29572
United States
Status: Recruiting Contact: N/A
Facility: Sarah Cannon Research Institute
Chattanooga, Tennessee 37404
United States
Status: Recruiting Contact: N/A
Facility: Texas Oncology - Fort Worth Cancer Center
Fort Worth, Texas 76104
United States
Status: Recruiting Contact: N/A
Facility: University of Texas Health Science Center at San Antonio
San Antonio, Texas 78229
United States
Status: Recruiting Contact: N/A
Facility: Texas Oncology - Tyler
Tyler, Texas 75702
United States
Status: Recruiting Contact: N/A
Facility: Utah Cancer Specialists
Salt Lake City, Utah 84106
United States
Status: Recruiting Contact: N/A
Facility: University of Virginia
Charlottesville, Virginia 22903
United States
Status: Recruiting Contact: N/A
Facility: Virginia Oncology Associates - Norfolk
Norfolk, Virginia 23502
United States
Status: Recruiting Contact: N/A
Facility: Medical Oncology Associates
Spokane, Washington 99208
United States
Status: Recruiting Contact: N/A
Facility: Medical College of Wisconsin (Milwaukee)
Milwaukee, Wisconsin 53226
United States
Status: Recruiting Contact: N/A
Facility: Site CA11008
East Brampton, Ontario L6R 3J7
Canada
Status: Recruiting Contact: N/A
Facility: Site CA11011
Kingston, Ontario K7L 2V7
Canada
Status: Recruiting Contact: N/A
Facility: Site CA11001
Toronto, Ontario M5G 2M9
Canada
Status: Recruiting Contact: N/A
Facility: Site CA11005
Montreal, Quebec H3T1E2
Canada
Status: Recruiting Contact: N/A
Facility: Site CA11013
Montreal, Quebec H4A3J1
Canada
Status: Recruiting Contact: N/A
Facility: Site CA11002
Sherbrooke, Quebec J1H 5N4
Canada
Status: Recruiting Contact: N/A
Facility: Site FR33008
Bordeaux, 33000
France
Status: Recruiting Contact: N/A
Facility: Site FR33003
Lyon, 69008
France
Status: Recruiting Contact: N/A
Facility: Site FR33002
Nice Cedex, 06189
France
Status: Recruiting Contact: N/A
Facility: Site FR33001
Strasbourg, 67200
France
Status: Recruiting Contact: N/A
Facility: Site PR78701
Rio Piedras, 00935
Puerto Rico
Status: Recruiting Contact: N/A