Treatment Combination of Durvalumab, Tremelimumab and Enfortumab Vedotin or Durvalumab and Enfortumab Vedotin in Patients With Muscle Invasive Bladder Cancer Ineligible to Cisplatin

Official Title

A Phase III Randomized, Open-Label, Multicentre Study to Determine the Efficacy and Safety of Durvalumab in Combination With Tremelimumab and Enfortumab Vedotin or Durvalumab in Combination With Enfortumab Vedotin for Perioperative Treatment in Patients Ineligible for Cisplatin Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer

Summary:

A Global Study to Determine the Efficacy and Safety of Durvalumab in combination with Tremelimumab and Enfortumab Vedotin or Durvalumab in Combination With Enfortumab Vedotin for Perioperative Treatment in Patients Ineligible for Cisplatin Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer

Trial Description

Primary Outcome:

• Safety and Tolerability as evaluated by adverse events occurring throughout the study
• Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by vital signs (blood pressure in mmHg)
• Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed ssessed by vital signs (pulse rate) in beats per minute
• Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by vital signs (respiration rate) in breaths per minute
• Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by vital signs (temperature) in degrees Celsius
• Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by abnormality in clinical chemistry by liver function
• Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by abnormality in clinical chemistry by kidney function
• Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by abnormality in clinical chemistry by thyroid function
• Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by abnormality in haematology
• Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by ECG (pulse rate)
• Changes in WHO/ECOG performance status
• Compare efficacy of durvalumab + tremelimumab + EV relative to cystectomy alone on pCR rate
• Compare efficacy of durvalumab + tremelimumab + EV relative to cystectomy alone on EFS

• 1.Pathologic complete response (pCR) rates at time of cystectomy in Arm 2 vs Arm 3
• 2.Event-free survival (EFS) defined as time from randomization to event in Arm 2 vs Arm 3
• 3.Overall survival
• 4.EFS at 24 months (EFS24)
• 5.Overall survival rate at 5 years
• 6.Disease-free survival (DFS)
• 7.Pathologic downstaging (pDS) rate-to < pT2
• 8.Disease-specific survival (DSS)
• 9.EORTC QLQ-C30 European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire)
• 10.Immunogenicity of durvalumab when used in combination with Tremelimumab as measured by presence of antidrug antibodies (ADA)
• 11.Area under the Plasma Concentration versus Time Curve (AUCτ) of durvalumab and tremelimumab
• 11.Time to maximum observed serum concentration (tmax) of durvalumab and tremelimumab

View this trial on ClinicalTrials.gov