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 (VOLGA)

AstraZeneca

Status and phase: Active, not recruiting; Phase 3

Conditions: Muscle Invasive Bladder Cancer

Treatments: Drug: Tremelimumab; Drug: Durvalumab; Procedure: Radical Cystectomy; Drug: Enfortumab Vedotin

Study type: Interventional

Funder types: Industry

Identifiers

NCT04960709

2020-005452-38 (EudraCT Number)

D910PC00001

Details and patient eligibility

About

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.

Full description

Not provided

Enrollment: 712 patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically documented muscle-invasive UC of the bladder.
• Participants with transitional cell and mixed transitional/non-transitional cell histologies;
• Participants with MIBC clinical tumor (T) stage T2-T4aN0/1M0 or UC of the bladder with clinical state T1N1M0 (participants with T1 stage are allowed only with N1 disease)
• Participants should also have not received prior systemic chemotherapy or immunotherapy for the treatment of MIBC or bladder UC.
• Medically fit for cystectomy and able to receive neoadjuvant therapy;
• Patients who have not received prior systemic chemotherapy or immunotherapy for treatment of MIBC;
• ECOG performance status of 0,1,2 at enrollment.
• Availability of tumor sample prior to study entry;
• Must have a life expectancy of at least 12 weeks at randomization.
• Cisplatin-ineligible, following criteria based on Galsky et al 2011 OR Refuse cisplatin based chemotherapy (must be documented in the medical records)

Exclusion criteria

• Evidence of lymph node (N2+) or metastatic TCC/UC disease at the time of screening.
• Active infection
• Uncontrolled intercurrent illness
• Prior exposure to immune-mediated therapy (with exclusion of Bacillus-Calmette Guerin [BCG]), including but not limited to other anti-CTLA-4, anti--PD-1, anti PD-L1, or anti-PD-L2 antibodies.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of IPs.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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712 participants in 3 patient groups

Durvalumab + Tremelimumab + Enfortumab Vedotin

Experimental group

Description:

Participants will receive 3 preoperative 21-day cycles of Durvalumab + Enfortumab Vedotin and 2 cycles of Tremelimumab, followed by radical cystectomy, followed by 1 cycle of postoperative Tremelimumab and 9 cycles of Durvalumab. Each postoperative cycle is 28 days.

Treatment:

Drug: Enfortumab Vedotin

Procedure: Radical Cystectomy

Drug: Durvalumab

Drug: Tremelimumab

Durvalumab + Enfortumab vedotin

Experimental group

Description:

Participants will receive 3 preoperative 21-day cycles of Durvalumab + Enfortumab Vedotin, followed by radical cystectomy, followed by 9 cycles of Durvalumab. Each postoperative cycle is 28 days.

Treatment:

Drug: Enfortumab Vedotin

Procedure: Radical Cystectomy

Drug: Durvalumab

Cystectomy with or without approved Adjuvant Therapy.

Active Comparator group

Description:

Participants may receive SoC (nivolumab approved as adjuvant treatment for MIBC based on high risk criteria) per approved label in the country OR Participants receive standard of care surgery (radical cystectomy) alone.

Treatment:

Procedure: Radical Cystectomy