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BRIEF TITLE: Study of Enfortumab Vedotin in Combination With Pembrolizumab With or Without Chemotherapy, Versus Chemotherapy Alone in Previously Untreated Locally Advanced or Metastatic Urothelial Cancer

An Open-label, Randomized, Controlled Phase 3 Study of Enfortumab Vedotin in Combination With Pembrolizumab With or Without Chemotherapy, Versus Chemotherapy Alone in Previously Untreated Locally Advanced or Metastatic Urothelial Cancer


  • Org Study ID: SGN22E-003
  • Secondary ID: 2019-004542-15,MK-3475-A39
  • NCT ID: NCT04223856
  • NCT Alias:
  • Sponsor: Astellas Pharma Global Development, Inc. - Industry
  • Source: Astellas Pharma Inc

Description

​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.

Brief Summary

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.

Detailed Description


This study is being conducted to evaluate the combination of enfortumab vedotin +
pembrolizumab, with or without platinum-containing chemotherapy, 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, carboplatin, and/or 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 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)

Primary Outcome 1 - Time Frame: Up to approximately 5 years

Primary Outcome 2 - Measure: Duration of Overall survival (OS)

Primary Outcome 2 - Time Frame: Up to approximately 5 years

Condition:

  • Urothelial Cancer

Eligibility

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 judgement

- 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 history of 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 3 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

Official Information

Name: Christina Derleth, MD, MSCI

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
Arizona Oncology Associates PD - HOPE
Tucson, Arizona 85710
United States
Recruiting
City of Hope National Medical Center
Duarte, California 91010
United States
Recruiting
Rocky Mountain Cancer Centers - Aurora
Aurora, Colorado 80012
United States
Recruiting
Eastern CT Hematology and Oncology Associates
Norwich, Connecticut 06360
United States
Recruiting
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida 33612
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
Toledo Clinic Cancer Center
Toledo, Ohio 43623
United States
Recruiting
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
Recruiting
UT Health East Texas Hope Cancer Center
Tyler, Texas 75701
United States
Recruiting
University of Virginia
Charlottesville, Virginia 22908
United States
Recruiting