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

Official 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

Summary:

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.

Trial Description

Primary Outcome:

• Duration of progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 by blinded independent central review (BICR) (Arms A and B only)
• Duration of Overall survival (OS) (Arms A and B only)

Secondary Outcome:

• Objective response rate (ORR) per RECIST v1.1 by BICR (Arms A and B only)
• Time to pain progression (TTPP) (Arms A and B only)
• Mean change from baseline in worst pain at Week 24 (Arms A and B only)
• Duration of PFS per RECIST v1.1 by investigator assessment (Arms A and B only)
• ORR per RECIST v1.1 by investigator assessment (Arms A and B only)
• Duration of response (DOR) per RECIST v1.1 by BICR (Arms A and B only)
• DOR per RECIST v1.1 by investigator assessment (Arms A and B only)
• Disease control rate (DCR) per RECIST v1.1 by BICR (Arms A and B only)
• DCR per RECIST v1.1 by investigator assessment (Arms A and B only)
• Change from baseline in patient reported outcome assessment measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L)
• Mean scores in patient reported outcome assessment measured by the EQ-5D-5L
• 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)
• Mean scores in patient reported outcome assessment measured by EORTC QLQ-C30
• Incidence of adverse events (AEs)
• Incidence of laboratory abnormalities
• Treatment discontinuation rate due to AEs

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.

View this trial on ClinicalTrials.gov