Enfortumab Vedotin und Pembrolizumab im Vergleich zu Chemotherapie allein bei Patienten mit unbehandeltem lokal fortgeschrittenem oder metastasiertem Urothelkarzinom

Drug: Enfortumab vedotin;Drug: Pembrolizumab;Drug: Cisplatin;Drug: Carboplatin;Drug: Gemcitabine

Gender: All
Maximum age: N/A
Minimum age: 18 Years

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