This study is being done to see how well two drugs (enfortumab vedotin and pembrolizumab) work together alone or with platinum chemotherapy 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.
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.
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.
Overal Status | Start Date | Phase | Study Type |
---|---|---|---|
Recruiting | March 30, 2020 | Phase 3 | Interventional |
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 - Time Frame: Up to approximately 5 years
Primary Outcome 2 - Measure: Duration of Overall survival (OS) (Arms and B only)
Primary Outcome 2 - Time Frame: Up to approximately 5 years
Criteria:
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
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Gender: All
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Christina Derleth, MD, MSCI
Role: Study Director
Affiliation: Seagen Inc.
Name: Seattle Genetics Trial Information Support
Phone: 866-333-7436
Email: clinicaltrials@seagen.com
Facility | Status | Contact |
---|---|---|
Ironwood Cancer & Research Centers - Chandler Chandler, Arizona 85224 United States |
Recruiting | |
Arizona Oncology Associates PD - HOPE Tucson, Arizona 85710 United States |
Completed | |
Providence St Joseph Medical Center Burbank, California 91505 United States |
Recruiting | |
City of Hope National Medical Center Duarte, California 91010 United States |
Recruiting | |
University of California Los Angeles Medical Center Los Angeles, California 90095 United States |
Recruiting | |
University of California Irvine - Newport Orange, California 92868 United States |
Recruiting | |
Rocky Mountain Cancer Centers - Aurora Aurora, Colorado 80012 United States |
Recruiting | |
University of Colorado Hospital / University of Colorado Aurora, Colorado 80045 United States |
Recruiting | |
Cancer Centers of Colorado - Denver Denver, Colorado 80218 United States |
Recruiting | |
Eastern CT Hematology and Oncology Associates Norwich, Connecticut 06360 United States |
Recruiting | |
Lombardi Cancer Center / Georgetown University Medical Center Washington, District of Columbia 20007 United States |
Recruiting | |
H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida 33612 United States |
Recruiting | |
Winship Cancer Institute / Emory University School of Medicine Atlanta, Georgia 30322 United States |
Recruiting | |
Georgia Cancer Specialists / Northside Hospital Cancer Institute Marietta, Georgia 30060 United States |
Recruiting | |
Louisiana State University/ East Jefferson General Hospital Metairie, Louisiana 70006 United States |
Recruiting | |
Maine Health Cancer Care Biddeford, Maine 04046 United States |
Recruiting | |
Johns Hopkins Medical Center Baltimore, Maryland 21231 United States |
Recruiting | |
Comprehensive Cancer Centers of Nevada Las Vegas, Nevada 89169 United States |
Recruiting | |
New Mexico Cancer Center Albuquerque, New Mexico 87109 United States |
Recruiting | |
Mount Sinai Medical Center New York, New York 10029 United States |
Recruiting | |
Memorial Sloan Kettering Cancer Center New York, New York 10065 United States |
Recruiting | |
Vidant Medical Center Greenville, North Carolina 27834 United States |
Recruiting | |
The Cleveland Clinic Cleveland, Ohio 44195 United States |
Recruiting | |
Toledo Clinic Cancer Center Toledo, Ohio 43623 United States |
Completed | |
Hillman Cancer Center / University of Pittsburgh Medical Center Pittsburgh, Pennsylvania 15232 United States |
Recruiting | |
Saint Francis Hospital / Bon Secours - South Carolina Greenville, South Carolina 29607 United States |
Completed | |
West Cancer Center & Research Institute Germantown, Tennessee 38138 United States |
Completed | |
University of Texas Southwestern Medical Center Dallas, Texas 75390 United States |
Recruiting | |
UT Health East Texas Hope Cancer Center Tyler, Texas 75701 United States |
Recruiting | |
Huntsman Cancer Institute Salt Lake City, Utah 84112 United States |
Recruiting | |
University of Virginia Charlottesville, Virginia 22908 United States |
Recruiting | |
Seattle Cancer Care Alliance / University of Washington Seattle, Washington 98109 United States |
Recruiting | |
Site CA11003 Edmonton, Alberta T6G 1Z2 Canada |
Recruiting | |
Site CA11009 London, Ontario N6A 5A5 Canada |
Recruiting | |
Site CA11001 Montreal, Quebec H3T 1E2 Canada |
Recruiting | |
Site SK82008 Hwasun, 519-763 Korea, Republic of |
Recruiting | |
Site ES34010 Barcelona, 08035 Spain |
Recruiting | |
Site ES34002 Madrid, 28034 Spain |
Recruiting | |
Site ES34004 Manresa, 08243 Spain |
Recruiting | |
Site ES34020 Pamplona, 31008 Spain |
Recruiting | |
Site ES34007 Sevilla, 41013 Spain |
Recruiting |