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Brief Title: Enfortumab Vedotin and Pembrolizumab vs. Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer

An Open-label, Randomized, Controlled Phase 3 Study of Enfortumab Vedotin in Combination With Pembrolizumab Versus Chemotherapy Alone in Previously Untreated Locally Advanced or Metastatic Urothelial Cancer

INTRODUCTION

  • Org Study ID: SGN22E-003
  • Secondary ID: 2019-004542-15, MK-3475-A39, KEYNOTE KN-A39, jRCT2031200284
  • NTC ID: NCT04223856
  • Sponsor: Astellas Pharma Global Development, Inc.

DESCRIPTION

This clinical trial uses a drug called enfortumab vedotin. The Food and Drug Administration (FDA) has approved enfortumab vedotin for sale in the US. It’s approved for adults with bladder cancer and cancers of the urinary tract (renal pelvis, ureter, or urethra) that has been treated before and that has spread or cannot be removed by surgery. 

We are studying enfortumab vedotin to find out if it works for your type of cancer when given with other drugs. We want to see if this drug combination works better than the available approved treatments. We also want to learn more about the side effects. A side effect is anything the drug does to your body besides treating your disease. We don’t yet know if enfortumab vedotin works better or worse than other treatments when combined with other drugs. Learning how this drug combination works and about the side effects will help us understand if it works better or worse than other treatments.

The drug we are using in this study in combination with enfortumab vedotin is pembrolizumab (brand name KEYTRUDA®). Pembrolizumab is approved by the FDA to treat several types of cancer, including cancer of the urinary system, in some people. This clinical trial also uses chemotherapy drugs such as cisplatin, carboplatin, and gemcitabine. These chemotherapy drugs are approved by the FDA for treating various cancers.

 

BRIEF SUMMARY

This study is being done to see how well two drugs (enfortumab vedotin and pembrolizumab) work together to treat patients with urothelial cancer. The study will compare these drugs to other drugs that are usually used to treat this cancer (standard of care). The patients in this study will have cancer that has spread from their urinary system to other parts of their body.

DETAILED DESCRIPTION

Japan PMDA has approved enfortumab vedotin (Padcev) for the treatment of advanced urothelial cancer. The study will continue as a post marketing study in Japan.

This study is being conducted to evaluate the combination of enfortumab vedotin + pembrolizumab versus standard of care gemcitabine + platinum-containing chemotherapy, in subjects with previously untreated locally advanced or metastatic urothelial cancer.

Enfortumab vedotin may be administered for an unlimited number of cycles until a protocol defined reason for study discontinuation occurs. Pembrolizumab may be administered for a maximum of 35 cycles or a protocol-defined reason for study discontinuation occurs, whichever is first. Cisplatin or carboplatin plus gemcitabine may be administered for a maximum of 6 cycles or a protocol-defined reason for study discontinuation occurs, whichever is first.

  • Overall Status
    Recruiting
  • Start Date
    March 30, 2020
  • Phase
    Phase 3
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Duration of progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent central review (BICR) (Arms A and B only)

Primary Outcome 1 - Timeframe: Up to approximately 5 years

Primary Outcome 2 - Measure: Duration of Overall survival (OS) (Arms and B only)

Primary Outcome 2 - Timeframe: Up to approximately 5 years

CONDITION

  • Urothelial Cancer

ELIGIBILITY

Inclusion Criteria:
Histologically documented, unresectable locally advanced or metastatic urothelial carcinoma
Measurable disease by investigator assessment according to RECIST v1.1
Participants with prior definitive radiation therapy must have measurable disease per RECIST v1.1 that is outside the radiation field or has demonstrated unequivocal progression since completion of radiation therapy
Participants must not have received prior systemic therapy for locally advanced or metastatic urothelial carcinoma with the following exceptions:
Participants that received neoadjuvant chemotherapy with recurrence >12 months from completion of therapy are permitted

- Participants that received adjuvant chemotherapy following cystectomy with recurrence >12 months from completion of therapy are permitted

- Must be considered eligible to receive cisplatin- or carboplatin-containing chemotherapy, in the investigator's judgment

- Archival tumor tissue comprising muscle-invasive urothelial carcinoma or a biopsy of metastatic urothelial carcinoma must be provided for PD-L1 testing prior to randomization

- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2

- Adequate hematologic and organ function
Exclusion Criteria
Previously received enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugate (ADCs)

- Received prior treatment with a programmed cell death ligand-1 (PD-(L)-1) inhibitor for any malignancy, including earlier stage urothelial cancer (UC), defined as a PD-1 inhibitor or PD-L1 inhibitor

- Received prior treatment with an agent directed to another stimulatory or co inhibitory T-cell receptor

- Received anti-cancer treatment with chemotherapy, biologics, or investigational agents not otherwise prohibited by exclusion criterion 1-3 that is not completed 4 weeks prior to first dose of study treatment

- Uncontrolled diabetes

- Estimated life expectancy of less than 12 weeks

- Active central nervous system (CNS) metastases

- Ongoing clinically significant toxicity associated with prior treatment that has not resolved to ≤ Grade 1 or returned to baseline

- Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis is permitted.

- Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection.

- History of another invasive malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy

- Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class IV within 6 months prior to randomization

- Receipt of radiotherapy within 2 weeks prior to randomization

- Received major surgery (defined as requiring general anesthesia and >24 hour inpatient hospitalization) within 4 weeks prior to randomization

- Known severe (≥ Grade 3) hypersensitivity to any enfortumab vedotin excipient contained in the drug formulation of enfortumab vedotin

- Active keratitis or corneal ulcerations

- History of autoimmune disease that has required systemic treatment in the past 2 years

- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan

- Prior allogeneic stem cell or solid organ transplant

- Received a live attenuated vaccine within 30 days prior to randomization

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Dominic Lai, MD

Role: Study Director

Affiliation: Seagen Inc.

Overall Contact

Name: Dominic Lai, MD

Phone: 866-333-7436

Email: clinicaltrials@seagen.com

LOCATION

Facility Status Contact
Facility: Providence St Joseph Medical Center
Burbank, California 91505
United States
Status: Recruiting Contact: N/A
Facility: City of Hope National Medical Center
Duarte, California 91010
United States
Status: Recruiting Contact: N/A
Facility: University of California Los Angeles Medical Center
Los Angeles, California 90095
United States
Status: Recruiting Contact: N/A
Facility: University of California Irvine - Newport
Orange, California 92868
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
United States
Status: Recruiting Contact: N/A
Facility: Cancer Centers of Colorado - Denver
Denver, Colorado 80218
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: Lombardi Cancer Center / Georgetown University Medical Center
Washington, District of Columbia 20007
United States
Status: Recruiting Contact: N/A
Facility: H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida 33612
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: Louisiana State University/ East Jefferson General Hospital
Metairie, Louisiana 70006
United States
Status: Recruiting Contact: N/A
Facility: Maine Health Cancer Care
Biddeford, Maine 04046
United States
Status: Recruiting Contact: N/A
Facility: Johns Hopkins Medical Center
Baltimore, Maryland 21231
United States
Status: Recruiting Contact: N/A
Facility: Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada 89169
United States
Status: Recruiting Contact: N/A
Facility: New Mexico Cancer Center
Albuquerque, New Mexico 87109
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: Mount Sinai Medical Center
New York, New York 10029
United States
Status: Recruiting Contact: N/A
Facility: Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
Status: Recruiting Contact: N/A
Facility: Vidant Medical Center
Greenville, North Carolina 27834
United States
Status: Recruiting Contact: N/A
Facility: The Cleveland Clinic
Cleveland, Ohio 44195
United States
Status: Recruiting Contact: N/A
Facility: University of Texas Southwestern Medical Center
Dallas, Texas 75390
United States
Status: Recruiting Contact: N/A
Facility: UT Health East Texas Hope Cancer Center
Tyler, Texas 75701
United States
Status: Recruiting Contact: N/A
Facility: Huntsman Cancer Institute
Salt Lake City, Utah 84112
United States
Status: Recruiting Contact: N/A
Facility: University of Virginia
Charlottesville, Virginia 22908
United States
Status: Recruiting Contact: N/A
Facility: Seattle Cancer Care Alliance / University of Washington
Seattle, Washington 98109
United States
Status: Recruiting Contact: N/A
Facility: Site AU61003
Box Hill, Alberta 3128
Australia
Status: Recruiting Contact: N/A
Facility: Site AUS61001
Douglas, Alberta 4814
Australia
Status: Recruiting Contact: N/A
Facility: Site AUS61004
Heidelberg, British Columbia 3084
Australia
Status: Recruiting Contact: N/A
Facility: Site AUS61002
Macquarie Park, Ontario 2109
Australia
Status: Recruiting Contact: N/A
Facility: Site AUS61006
South Australia, Ontario 5112
Australia
Status: Recruiting Contact: N/A
Facility: Site BE32003
Brussels, Ontario 1200
Belgium
Status: Recruiting Contact: N/A
Facility: Site BE32002
Ghent, Ontario 9000
Belgium
Status: Recruiting Contact: N/A
Facility: Site BE 32001
Liege, Quebec 4000
Belgium
Status: Recruiting Contact: N/A
Facility: Site BE32006
Roeselare, Quebec 8800
Belgium
Status: Recruiting Contact: N/A
Facility: Site CA11004
Calgary, T2N 4N2
Canada
Status: Recruiting Contact: N/A
Facility: Site CA11003
Edmonton, T6G 1Z2
Canada
Status: Recruiting Contact: N/A
Facility: Site CA11006
Vancouver, V5Z 4E6
Canada
Status: Recruiting Contact: N/A
Facility: Site CA11002
Hamilton, L8V 1C3
Canada
Status: Recruiting Contact: N/A
Facility: Site CA11009
London, N6A 5A5
Canada
Status: Recruiting Contact: N/A
Facility: Site CA11011
Oshawa, L1G 2B9
Canada
Status: Recruiting Contact: N/A
Facility: Site CA11005
Toronto, M5G 2M9
Canada
Status: Recruiting Contact: N/A
Facility: Site CA11010
Montreal, H2X 0A9
Canada
Status: Recruiting Contact: N/A
Facility: Site CA11001
Montreal, H3T 1E2
Canada
Status: Recruiting Contact: N/A
Facility: Site CA11008
Quebec, G1R 2J6
Canada
Status: Recruiting Contact: N/A
Facility: Site CA11012
Toronto, M4N 3M5
Canada
Status: Recruiting Contact: N/A
Facility: Site CN86001
Beijing, 100036
China
Status: Recruiting Contact: N/A
Facility: Site DK45001
Aalborg, 9100
Denmark
Status: Recruiting Contact: N/A
Facility: Site FR33016
Lyon, 69373
France
Status: Recruiting Contact: N/A
Facility: Site FR33011
Villejuif-Cedex-France, 94805
France
Status: Recruiting Contact: N/A
Facility: Site DE49013
Bielefeld, 33611
Germany
Status: Recruiting Contact: N/A
Facility: Site DE49007
Frankfurt am Main, 60488
Germany
Status: Recruiting Contact: N/A
Facility: Site DE49004
Tübingen, 72076
Germany
Status: Recruiting Contact: N/A
Facility: Site HU36002
Budapest, 1122
Hungary
Status: Recruiting Contact: N/A
Facility: Site HU36001
Nyiregyhaza, 4400
Hungary
Status: Recruiting Contact: N/A
Facility: Site IT39005
Areezo, 52100
Italy
Status: Recruiting Contact: N/A
Facility: Site IT39008
Candiolo, 10060
Italy
Status: Recruiting Contact: N/A
Facility: Site IT39006
Genova, 16132
Italy
Status: Recruiting Contact: N/A
Facility: Site IT39004
Pisa, 56126
Italy
Status: Recruiting Contact: N/A
Facility: Site IT39002
Terni, 05100
Italy
Status: Recruiting Contact: N/A
Facility: Site IT39001
Verona, 37134
Italy
Status: Recruiting Contact: N/A
Facility: Site JP81002
Bunkyo City, 301-721
Japan
Status: Recruiting Contact: N/A
Facility: Site JP81009
Chiba, 10408
Japan
Status: Recruiting Contact: N/A
Facility: Site JP81006
Kawasaki-shi, 519-763
Japan
Status: Recruiting Contact: N/A
Facility: Site JP81001
Koto-ku, 13605
Japan
Status: Recruiting Contact: N/A
Facility: Site JP81005
Okayama, 03722
Japan
Status: Recruiting Contact: N/A
Facility: Site JP81003
Toyama, 05505
Japan
Status: Recruiting Contact: N/A
Facility: Site JP81004
Tsukuba, 135-710
Japan
Status: Recruiting Contact: N/A
Facility: Site KR82001
Daejeon, 137-701
Korea, Republic of
Status: Recruiting Contact: N/A
Facility: Site KR82002
Goyang-si, 1066 CX
Korea, Republic of
Status: Recruiting Contact: N/A
Facility: Site SK82008
Hwasun, 1066 CX
Korea, Republic of
Status: Recruiting Contact: N/A
Facility: Site KR82004
Seongnam-si, 8934 AD
Korea, Republic of
Status: Recruiting Contact: N/A
Facility: Site KR82003
Seoul, 3435 CM
Korea, Republic of
Status: Recruiting Contact: N/A
Facility: Site KR82005
Seoul, 3584 CX
Korea, Republic of
Status: Recruiting Contact: N/A
Facility: Site KR82007
Seoul, 163045
Korea, Republic of
Status: Recruiting Contact: N/A
Facility: Site KR82006
Seoul, 656049
Korea, Republic of
Status: Recruiting Contact: N/A
Facility: Site NL31005
Amsterdam, Noord-Holland, 660133
Netherlands
Status: Recruiting Contact: N/A
Facility: Site NL31002
Amsterdam, 188663
Netherlands
Status: Recruiting Contact: N/A
Facility: Site NL31007
Leeuwarden, 123056
Netherlands
Status: Recruiting Contact: N/A
Facility: Site NL31004
Nieuwegein, 125284
Netherlands
Status: Recruiting Contact: N/A
Facility: Site NL31006
Utrecht, 644013
Netherlands
Status: Recruiting Contact: N/A
Facility: Site RU70016
Arkhangelsk, 195271
Russian Federation
Status: Recruiting Contact: N/A
Facility: Site RU70013
Barnaul, 197082
Russian Federation
Status: Recruiting Contact: N/A
Facility: Site RU70014
Krasnoyarsk, 430032
Russian Federation
Status: Recruiting Contact: N/A
Facility: Site RU70006
Leningradskaya Oblast', 450000
Russian Federation
Status: Recruiting Contact: N/A
Facility: Site RU70011
Moscow, 08003
Russian Federation
Status: Recruiting Contact: N/A
Facility: Site RU70003
Moscow, 08035
Russian Federation
Status: Recruiting Contact: N/A
Facility: Site RU70002
Omsk, 08041
Russian Federation
Status: Recruiting Contact: N/A
Facility: Site RU70010
Saint Petersburg, 14004
Russian Federation
Status: Recruiting Contact: N/A
Facility: Site RU70007
Saint Petersburg, 27003
Russian Federation
Status: Recruiting Contact: N/A
Facility: Site RU70009
Saransk, 28034
Russian Federation
Status: Recruiting Contact: N/A
Facility: Site RU70005
Ufa, 08243
Russian Federation
Status: Recruiting Contact: N/A
Facility: Site SP34017
Barcelona, 31008
Spain
Status: Recruiting Contact: N/A
Facility: Site ES34010
Barcelona, 08208
Spain
Status: Recruiting Contact: N/A
Facility: Site SP34001
Barcelona, 39008
Spain
Status: Recruiting Contact: N/A
Facility: Site ES34013
Cordoba, 41013
Spain
Status: Recruiting Contact: N/A
Facility: Site ES34021
Lugo, 46009
Spain
Status: Recruiting Contact: N/A
Facility: Site ES34002
Madrid, 3010
Spain
Status: Recruiting Contact: N/A
Facility: Site ES34004
Manresa, 7000
Spain
Status: Recruiting Contact: N/A
Facility: Site ES34020
Pamplona, 8401
Spain
Status: Recruiting Contact: N/A
Facility: Site SP34016
Sabadell, 40447
Spain
Status: Recruiting Contact: N/A
Facility: Site SP34012
Santander, 40705
Spain
Status: Recruiting Contact: N/A
Facility: Site ES34007
Sevilla, 70403
Spain
Status: Recruiting Contact: N/A
Facility: Site ES34019
Valencia, 10002
Spain
Status: Recruiting Contact: N/A
Facility: Site CH41002
Bern, 11217
Switzerland
Status: Recruiting Contact: N/A
Facility: Site CH41001
Chur, EC1M 6BQ
Switzerland
Status: Recruiting Contact: N/A
Facility: Site CH41003
Winterthur, PR2 9HT
Switzerland
Status: Recruiting Contact: N/A
Facility: Site TW88607
Taichung,
Taiwan
Status: Recruiting Contact: N/A
Facility: Site TW88606
Taichung,
Taiwan
Status: Recruiting Contact: N/A
Facility: Site TW88604
Tainan,
Taiwan
Status: Recruiting Contact: N/A
Facility: Site TW88605
Taipei,
Taiwan
Status: Recruiting Contact: N/A
Facility: Site TW88601
Taipei,
Taiwan
Status: Recruiting Contact: N/A
Facility: Site UK44001
London,
United Kingdom
Status: Recruiting Contact: N/A
Facility: Site UK44002
Preston,
United Kingdom
Status: Recruiting Contact: N/A