Resumen

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.

Descripción detallada

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.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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

Criterios de exclusión

Prior allogeneic stem cell or solid organ transplant
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
Received a live attenuated vaccine within 30 days prior to randomization

Intervenciones

drug

Enfortumab vedotin

Enfortumab vedotin administered as an IV infusion on Days 1 and 8 of every 3-week cycle

drug

Pembrolizumab

IV infusion on Day 1 of every 3-week cycle

drug

Cisplatin

administered as IV infusion on Day 1 of each 3-week cycle

drug

Carboplatin

Dosed according to local guidelines and will be administered as IV infusion on Day 1 of each 3-week cycle

drug

Gemcitabine

IV infusion on Days 1 and 8 of every 3 week cycle

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

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Enfortumab vedotin

Pembrolizumab

Cisplatin

Carboplatin

Gemcitabine

Ubicaciones

Site AR54008

Site AR54011

Site AR54005

Site AR54006

Site AR54004

Site AR54001

Site AR54002

Site AR54012

Site AR54003

Patrocinadores