What is the mechanism of action of this treatment?

Bladder cancer treatments often include immune checkpoint inhibitors like Durvalumab and Tremelimumab, and targeted therapies such as Enfortumab Vedotin. Immune checkpoint inhibitors work by blocking proteins (PD-1, PD-L1, and CTLA-4) that prevent the immune system from attacking cancer cells, thereby enhancing the body's immune response against the tumor. Enfortumab Vedotin is an antibody-drug conjugate that targets Nectin-4, a protein commonly found on bladder cancer cells, delivering cytotoxic agents directly to the tumor. These treatments are crucial for bladder cancer patients as they offer targeted approaches that can improve survival rates and provide options for those who may not respond to traditional chemotherapy.

What side effects are associated with this type of intervention?

The combination of Durvalumab, Tremelimumab, and Enfortumab Vedotin for bladder cancer treatment can lead to a range of side effects. Immune checkpoint inhibitors like Durvalumab and Tremelimumab are associated with immune-related adverse events such as pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Enfortumab Vedotin, a targeted therapy, can cause peripheral neuropathy, rash, fatigue, and hyperglycemia. When these treatments are combined, there may be an increased risk and severity of these side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for bladder cancer that are similar to the combination of Durvalumab, Tremelimumab, and Enfortumab Vedotin. Immune checkpoint inhibitors such as Pembrolizumab and Atezolizumab have been approved for patients with advanced urothelial carcinoma, particularly those who have progressed after platinum-based chemotherapy. Additionally, Enfortumab Vedotin, an antibody-drug conjugate targeting Nectin-4, has been approved for patients who have previously received PD-1 or PD-L1 inhibitors and platinum-based chemotherapy. These treatments underscore the efficacy of immune checkpoint inhibition and targeted therapy in managing advanced bladder cancer.

What other types of research exist?

Promising novel alternatives for bladder cancer treatment in 2024 include: 1) Pembrolizumab combined with chemotherapy (e.g., paclitaxel, docetaxel, or vinflunine) as second-line therapy, 2) Atezolizumab as monotherapy or in combination with chemotherapy for platinum-treated patients, 3) Enfortumab Vedotin as monotherapy for patients previously treated with PD-1/PD-L1 inhibitors, and 4) Sacituzumab Govitecan for patients progressing after platinum-based chemotherapy and checkpoint inhibitors.

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Checkpoint Inhibitor

Durvalumab + Tremelimumab + Enfortumab Vedotin for Bladder Cancer (VOLGA Trial)

Phase 3

Recruiting

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients who have not received prior systemic chemotherapy or immunotherapy for treatment of MIBC

Participants with MIBC clinical tumor (T) stage T2-T4aN0/1M0 or UC of the bladder with clinical state T1N1M0

Must not have

Evidence of lymph node (N2+) or metastatic TCC/UC disease at the time of screening

Active infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at 5 years

Awards & highlights

Summary

This trial tests a new combination of cancer treatments for bladder cancer patients who can't use standard chemotherapy. It uses drugs that help the immune system fight cancer and a drug that targets and kills cancer cells directly.

Who is the study for?

This trial is for adults with muscle invasive bladder cancer who can't use or refuse cisplatin, haven't had chemo or immunotherapy for it, and are fit enough for cystectomy surgery. They must have a life expectancy of at least 12 weeks and be able to provide a tumor sample.

What is being tested?

The study tests Durvalumab combined with Tremelimumab and Enfortumab Vedotin versus Durvalumab with Enfortumab Vedotin alone in patients undergoing surgery. It's randomized, meaning treatment is assigned by chance, aiming to improve current treatments.

What are the potential side effects?

Possible side effects include immune-related reactions affecting organs, infusion-related symptoms like fever or chills, fatigue, skin issues, potential liver problems (hepatitis), and an increased risk of infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have not had chemotherapy or immunotherapy for my bladder cancer.

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My bladder cancer is at a specific stage but hasn't spread far.

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I have not had chemotherapy or immunotherapy for bladder cancer.

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I can take care of myself and am up and about more than half of my waking hours.

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My cancer is of a type that involves certain cells in the bladder or urinary tract.

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My bladder cancer is confirmed by lab tests and is invasive.

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I cannot take cisplatin or have chosen not to, as noted in my medical records.

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I am healthy enough for bladder removal surgery and can undergo treatment before surgery.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My cancer has spread to lymph nodes or is metastatic.

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I currently have an infection.

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I do not have any unmanaged ongoing illnesses.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and at 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Changes in WHO/ECOG performance status (Safety Run-In part)

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)

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)

+4 more

Secondary study objectives

1. To evaluate the efficacy of durvalumab + tremelimumab + EV on pCR rate (Safety Run-in part)

13. Metastasis-free survival (MFS) (Safety Run-in and Main Study part)

2. To evaluate the efficacy of durvalumab + tremelimumab + EV on EFS (Safety Run-in part)

+7 more

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Durvalumab + Tremelimumab + Enfortumab vedotinExperimental Treatment4 Interventions

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

Group II: Durvalumab + Enfortumab vedotinExperimental Treatment3 Interventions

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.

Group III: Cystectomy with or without approved Adjuvant Therapy.Active Control1 Intervention

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

First Studied

Drug Approval Stage

How many patients have taken this drug

Durvalumab

2017

Completed Phase 2

~3840

Tremelimumab

2017

Completed Phase 2

~3130

Radical Cystectomy

2006

Completed Phase 2

~140

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Bladder cancer treatments often include immune checkpoint inhibitors like Durvalumab and Tremelimumab, and targeted therapies such as Enfortumab Vedotin. Immune checkpoint inhibitors work by blocking proteins (PD-1, PD-L1, and CTLA-4) that prevent the immune system from attacking cancer cells, thereby enhancing the body's immune response against the tumor. Enfortumab Vedotin is an antibody-drug conjugate that targets Nectin-4, a protein commonly found on bladder cancer cells, delivering cytotoxic agents directly to the tumor. These treatments are crucial for bladder cancer patients as they offer targeted approaches that can improve survival rates and provide options for those who may not respond to traditional chemotherapy.

[The role of immunotherapy in the modern treatment of urothelial carcinoma].