What is the mechanism of action of this treatment?

The most common treatments for bladder cancer include immunotherapy and targeted therapy. Durvalumab, a PD-L1 inhibitor, enhances the immune response by blocking the interaction between PD-L1 on tumor cells and PD-1 on T-cells, allowing the immune system to better recognize and attack cancer cells. Olaparib, a PARP inhibitor, prevents cancer cells from repairing their DNA, leading to cell death, especially in cells already deficient in DNA repair mechanisms. These targeted approaches are significant for bladder cancer patients as they can improve treatment efficacy and reduce side effects compared to traditional chemotherapy.

What side effects are associated with this type of intervention?

Common side effects of Durvalumab, a PD-L1 inhibitor, include fatigue, decreased appetite, nausea, and immune-related adverse events such as pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Olaparib, a PARP inhibitor, is associated with side effects such as nausea, fatigue, anemia, vomiting, and more severe hematologic toxicities like thrombocytopenia and neutropenia. Both drugs can cause serious but less common side effects, and patients should be monitored closely during treatment.

What prior FDA approvals exist?

For the treatment of bladder cancer, the FDA has approved several PD-L1 inhibitors, including Atezolizumab and Pembrolizumab. Atezolizumab was approved for patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy. Pembrolizumab has been approved for similar indications, including as a first-line treatment for cisplatin-ineligible patients. While PARP inhibitors like Olaparib are being studied in clinical trials for bladder cancer, they have not yet received FDA approval specifically for this indication.

What other types of research exist?

Promising novel alternatives to Durvalumab and Olaparib for bladder cancer patients include: 1) Atezolizumab, another PD-L1 inhibitor, which has shown efficacy in platinum-treated advanced urothelial carcinoma. 2) Enfortumab Vedotin, an antibody-drug conjugate targeting Nectin-4, which has demonstrated significant activity in patients previously treated with PD-1/PD-L1 inhibitors. 3) Sacituzumab Govitecan, a Trop-2 directed antibody-drug conjugate, which has shown promising results in metastatic urothelial carcinoma after prior chemotherapy and checkpoint inhibitor therapy. These alternatives offer different mechanisms of action and have shown potential in recent clinical trials.

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Durvalumab + Olaparib for Bladder Cancer (BAYOU Trial)

Phase 2

Waitlist Available

Led By Jonathan Rosenberg, MD

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

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

Must have

Ineligibility for platinum-based chemotherapy as defined by specific criteria

Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients

Must not have

Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment

Active or prior documented autoimmune or inflammatory disorders

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Summary

This trial tests a combination of two drugs, durvalumab and olaparib, for patients with advanced bladder cancer who can't receive standard chemotherapy. Durvalumab helps the immune system attack cancer, while olaparib makes it harder for cancer cells to repair themselves. The goal is to see if this combination is more effective than using durvalumab alone.

Who is the study for?

This trial is for adults with advanced bladder cancer that can't be surgically removed and who haven't had systemic therapy. They must not qualify for platinum-based chemotherapy, have a certain performance status, and be able to take oral meds. Pregnant or breastfeeding individuals, those with autoimmune diseases, recent major surgery, uncontrolled illnesses, or prior treatments with similar drugs are excluded.

What is being tested?

The BAYOU study is testing the effectiveness of Durvalumab alone versus its combination with Olaparib against bladder cancer in patients ineligible for platinum chemo. It's a phase II trial where participants are randomly assigned to receive either both drugs or one drug plus a placebo without knowing which they're getting.

What are the potential side effects?

Durvalumab may cause immune-related issues like inflammation in various organs and infusion reactions. Olaparib could lead to blood cell count changes, nausea, fatigue among other side effects. The combination might increase these risks.

Eligibility Criteria

Inclusion Criteria

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

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I cannot receive platinum-based chemotherapy due to certain conditions.

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I am post-menopausal or not currently pregnant.

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My bladder cancer is advanced and hasn't been treated with systemic therapy.

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I can swallow pills.

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I can take care of myself and perform daily activities.

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I know my tumor's HRR mutation status.

Exclusion Criteria

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

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I am not currently on any cancer treatments like chemotherapy or hormone therapy.

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I have or had an autoimmune or inflammatory disorder.

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I do not have an active infection, including TB.

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I have not undergone radiation therapy, or I meet specific criteria for it.

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I haven't taken immunosuppressive drugs in the last 14 days.

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I have received an organ transplant from another person.

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I have not had major surgery in the last 28 days.

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I have previously been treated with a PARP inhibitor or immunotherapy.

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I do not have any unmanaged ongoing illnesses.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 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

Progression-free Survival (PFS)

Secondary study objectives

Duration of Response (DoR)

Objective Response Rate (ORR)

Overall Survival (OS)

Other study objectives

Changes in WHO/ECOG performance status

Number of Participants with Treatment-Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE)

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm 2: Durvalumab/OlaparibExperimental Treatment2 Interventions

Durvalumab 1500 mg IV q4w starting on week 1 day 1/Olaparib PO 300 mg BID adjusted based on patient's creatinine clearance.

Group II: Arm 1: Durvalumab/PlaceboExperimental Treatment2 Interventions

Durvalumab 1500 mg intravenous (IV) every 4 weeks (q4w) starting on week 1 day 1/Placebo orally (PO) twice a day (BID) starting on week 1 day 1.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Durvalumab

2017

Completed Phase 2

~3750

Olaparib

2007

Completed Phase 4

~2190

Placebo

1995

Completed Phase 3

~2670

0 / 15Eligibility 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

The most common treatments for bladder cancer include immunotherapy and targeted therapy. Durvalumab, a PD-L1 inhibitor, enhances the immune response by blocking the interaction between PD-L1 on tumor cells and PD-1 on T-cells, allowing the immune system to better recognize and attack cancer cells. Olaparib, a PARP inhibitor, prevents cancer cells from repairing their DNA, leading to cell death, especially in cells already deficient in DNA repair mechanisms. These targeted approaches are significant for bladder cancer patients as they can improve treatment efficacy and reduce side effects compared to traditional chemotherapy.

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