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

Condition(s) studied

Investigational drug(s) / intervention(s)

Durvalumab: Anti- PD-L1 Antibody

Tremelimumab: Human IgG2 mAb

Enfortumab Vedotin: Nectin-4-directed antibody and microtubule inhibitor conjugate

Radical Cystectomy: For cisplatin-ineligible or cisplatin-refusal patients

Study summary

A global phase 3, multicenter, randomized, trial, 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 or who refuse Cisplatin based chemotherapy Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer.

The goal of the study is to explore the triplet combination of Durvalumab, Tremelimumab and Enfortumab Vedotin or the duplet combination of Durvalumab and Enfortumab vedotin in terms of efficacy and safety compared to the current Standard Of Care (SOC).

VOLGA trial consists of two parts: Safety Run-In and Main Study. In total the study aims to enroll approximately 677 patients, who will receive triplet combination, duplet combination or currently approved SOC in the main study. In the main part of the trial there is two out of three chances of being on a treatment arm and the treatment is assigned at random by a computer system.

In this trial patients in the two treatment arms will receive either 3 cycles of neoadjuvant Durvalumab + Enfortumab Vedotin and 2 cycles of Tremelimumab or Durvalumab + Enfortumab vedotin and after surgery both treatment arms will receive either adjuvant Durvalumab or adjuvant Durvalumab and 1 cycle of Tremelimumab.

Eligibility

Primary outcome measure(s)

• To assess the safety and tolerability as evaluated by adverse events occurring throughout the study (Safety Run-In part) — At completion of study treatment by the last patient and at 3 months.
  Frequency of Adverse Events.
• To assess the 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 Run-In part) — Up to 84 months
• To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by vital signs (pulse rate) in beats per minute (Safety Run-In part) — Up to 84 months
• To assess the 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 Run-In part) — Up to 84 months
• To assess the 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 Run-In part) — Up to 84 months
• To assess the 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 Run-In part) — Up to 84 months
  Clinical chemistry will be assessed by liver function assessment (ALT, AST, albumin, total bilirubin measured in units per dL)
• Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin or who refuse cisplatin as assessed by abnormality in clinical chemistry by kidney function (Safety Run-In part) — Up to 84 months
  Clinical chemistry will be assessed by kidney function assessment in mg/dL
• To assess the 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 Run-In part) — Up to 84 months
  Clinical chemistry will be assessed by thyroid function assessment in units per mL.
• To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by abnormality in haematology (Safety Run-In part) — Up to 84 months
  Hematology will be assessed by white cell count, platelet count, absolute neutrophil count and absolute lymphocyte count.
• To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as as assessed by ECG (pulse rate) (Safety Run-In part) — Up to 84 months
• Changes in WHO/ECOG performance status (Safety Run-In part) — Up to 84 months
  Eastern Cooperative Oncology Group (ECOG) performance status scale range 0 to 5, where 0 is fully active, able to carry on all pre disease performance without restriction - best outcome and 5 -death - worst outcome.
• Compare efficacy of durvalumab + tremelimumab + EV (Arm 1) relative to cystectomy (Arm 3) and durvalumab + EV (Arm 2) relative to cystectomy (Arm 3) on EFS (Main Study) — Up to 3 years
  Event-free survival (EFS;) is defined as the time from randomization to the first occurrence of any of the following events: recurrence of disease post-radical cystectomy, the first documented progression in participants who did not receive radical cystectomy, failure to undergo radical cystectomy in participants with residual disease, or death due to any cause, up to 3 years.

Trial sites (196)

+ 156 more sites — see the full list on the official registry below.

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