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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 December 2023
• Main ID: NCT04223856
• Date of registration: 06/01/2020
• Prospective Registration: Yes
• Primary sponsor: Astellas Pharma Global Development, Inc.
• Public title: Enfortumab Vedotin and Pembrolizumab vs. Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer EV-302
• Scientific title: 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
• Date of first enrolment: March 30, 2020
• Target sample size: 990
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT04223856
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Belgium, Canada, China, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Russian Federation, Singapore, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: John Lu, MD
• Affiliation: Seagen Inc.

• Name: Zejing Wang, MD, PhD
• Affiliation: Seagen Inc.

• Name: Seagen Inc. Trial Information Support

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Urothelial Cancer

Intervention(s)

Drug: Gemcitabine

Drug: Pembrolizumab

Drug: Cisplatin

Drug: Enfortumab vedotin

Drug: Carboplatin

Primary Outcome(s)

Duration of Overall survival (OS) (Arms A and B only, global population) [Time Frame: Up to approximately 5 years]

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, global population) [Time Frame: Up to approximately 5 years]

Secondary Outcome(s)

Mean scores in patient reported outcome assessment measured by EORTC QLQ-C30 [Time Frame: Up to approximately 5 years]

DOR per RECIST v1.1 by investigator assessment (Arms A and B only) [Time Frame: Up to approximately 5 years]

Objective response rate (ORR) per RECIST v1.1 by BICR (Arms A and B only) [Time Frame: Up to approximately 5 years]

Incidence of adverse events (AEs) [Time Frame: Up to approximately 5 years]

ORR per RECIST v1.1 by investigator assessment (Arms A and B only) [Time Frame: Up to approximately 5 years]

DCR per RECIST v1.1 by investigator assessment (Arms A and B only) [Time Frame: Up to approximately 5 years]

Mean scores in patient reported outcome assessment measured by the EQ-5D-5L [Time Frame: Up to approximately 5 years]

Change from baseline in patient reported outcome assessment measured by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) [Time Frame: Up to approximately 5 years]

Disease control rate (DCR) per RECIST v1.1 by BICR (Arms A and B only) [Time Frame: Up to approximately 5 years]

Duration of response (DOR) per RECIST v1.1 by BICR (Arms A and B only) [Time Frame: Up to approximately 5 years]

Change from baseline in patient reported outcome assessment measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L) [Time Frame: Up to approximately 5 years]

Duration of PFS per RECIST v1.1 by investigator assessment (Arms A and B only) [Time Frame: Up to approximately 5 years]

Treatment discontinuation rate due to AEs [Time Frame: Up to approximately 5 years]

Incidence of laboratory abnormalities [Time Frame: Up to approximately 5 years]

Mean change from baseline in worst pain at Week 26 (Arms A and B only) [Time Frame: Up to approximately 6 months]

Time to pain progression (TTPP) (Arms A and B only) [Time Frame: Up to approximately 5 years]

Secondary ID(s)

KEYNOTE KN-A39

SGN22E-003

MK-3475-A39

2019-004542-15

CTR20220974

jRCT2031200284

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Merck Sharp & Dohme LLC

Seagen Inc.