What side effects are associated with this type of intervention?

Common treatments for bladder cancer, particularly those involving PD-L1 inhibitors like Durvalumab and immune system stimulants like BCG, can have several side effects. Durvalumab, a PD-L1 inhibitor, may cause immune-related adverse events such as skin reactions, endocrine disorders, and pneumonitis. BCG therapy, which stimulates the immune system, can lead to local side effects like cystitis, hematuria, and systemic symptoms such as fever and malaise. Combining these treatments may increase the risk of immune-related side effects, necessitating close monitoring and management.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of bladder cancer that involve PD-L1 inhibition and immune system stimulation. Notably, Atezolizumab and Pembrolizumab are immune checkpoint inhibitors targeting PD-L1 and PD-1, respectively. These drugs enhance the immune system's ability to fight cancer by blocking the proteins that prevent T-cells from attacking cancer cells. Atezolizumab was approved for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin chemotherapy, while Pembrolizumab has been approved for similar indications, including as a second-line treatment after chemotherapy. These approvals highlight the growing role of immunotherapy in bladder cancer treatment, similar to the investigational combination of Durvalumab (another PD-L1 inhibitor) and BCG.

What other types of research exist?

Promising novel alternatives to Durvalumab + BCG for bladder cancer patients include: 1) Pembrolizumab (PD-1 inhibitor) as second-line therapy for advanced urothelial carcinoma, which has shown efficacy in the KEYNOTE-045 trial. 2) Nivolumab (PD-1 inhibitor) monotherapy, which has demonstrated positive outcomes in the CheckMate 032 and CheckMate 275 trials. 3) Atezolizumab (PD-L1 inhibitor) as an alternative, supported by long-term survival data from the IMvigor211 trial. 4) Enfortumab Vedotin, an antibody-drug conjugate targeting Nectin-4, which has shown promising results in patients previously treated with PD-1/PD-L1 inhibitors.

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Cancer Vaccine

Durvalumab + BCG for Bladder Cancer (POTOMAC Trial)

Phase 3

Waitlist Available

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

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

Must have

Aged at least 18 years

Local histological confirmation (based on pathology report) of high-risk transitional cell carcinoma of the urothelium of the urinary bladder confined to the mucosa or submucosa. A high risk tumor is defined as one of the following: T1 tumor, High grade/ G3 tumor, CIS, Multiple and recurrent and large (with diameter of largest tumor ≥3 cm) tumors (all conditions must be met in this point)

Must not have

Concurrent extravesical (ie, urethra, ureter, or renal pelvis), non-muscle-invasive transitional cell carcinoma of the urothelium

Evidence of muscle-invasive, locally advanced, metastatic, and/or extra vesical bladder cancer (ie, T2, T3, T4, and / or stage IV)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 4 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a new treatment that combines two therapies to help the immune system fight bladder cancer. It targets patients whose cancer has not spread into the muscle layer of the bladder. The treatment works by helping the body's defense system recognize and destroy cancer cells more effectively.

Who is the study for?

This trial is for adults with high-risk non-muscle-invasive bladder cancer who haven't had immune therapy or BCG for bladder cancer, and no recent immunosuppressants. It's not for those with muscle-invasive or advanced cancer, certain autoimmune diseases, or a history of other cancers (with some exceptions).

What is being tested?

The study tests Durvalumab combined with BCG against standard BCG treatment alone in patients with bladder cancer that hasn't invaded the muscle layer. The goal is to see if adding Durvalumab improves outcomes.

What are the potential side effects?

Durvalumab may cause immune-related side effects like inflammation in various organs, skin reactions, hormone gland problems (like thyroid issues), and could worsen pre-existing autoimmune conditions.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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My bladder cancer is high-risk but hasn't spread beyond the inner layers.

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I have not had radiation therapy for bladder cancer.

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I have not received any immune therapy for cancer, including vaccines.

Exclusion Criteria

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

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I have bladder cancer that has not spread to my muscles but may be in my urethra, ureter, or kidney.

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My bladder cancer is advanced or has spread beyond the bladder.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 4 years for reporting.

Treatment Details

Study Objectives

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

Secondary study objectives

Disease-related symptoms and HRQoL in patients with NMIBC treated with Durvalumab + BCG combination therapies compared to SoC and compared to each other using the EORTC QLQ-C30 questionnaire

Disease-related symptoms and HRQoL in patients with NMIBC treated with Durvalumab + BCG combination therapies compared to SoC and compared to each other using the the EORTC QLQ NMIBC24 questionnaire

The efficacy of durvalumab + BCG combination therapy compared to SoC in terms of CRR for patients with CIS prior to study entry or at baseline cystoscopy

+1 more

Other study objectives

Number of treatment-related adverse events as assessed by CTCAE v4.0 in patients receiving Durvalumab + BCG combination therapies compared to SoC

Side effects data

From 2022 Phase 2 trial • 20 Patients • NCT04507126

25%

Post Lumbar Puncture Headache

19%

Back pain

13%

Fatigue

13%

Intermittent headache

Increased stress

Removal of squamous cell carcinoma

Hematoma at blood draw site

Contact dermatitis

100%

80%

60%

40%

20%

Study treatment Arm

BCG Immunization

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Durvalumab plus BCG (induction only)Experimental Treatment2 Interventions

Durvalumab (MEDI4736) plus Bacillus Calmette-Guerrin (BCG) combination therapy

Group II: Durvalumab plus BCG (induction + maintenance)Experimental Treatment2 Interventions

Durvalumab (MEDI4736) plus Bacillus Calmette-Guerrin (BCG) combination therapy

Group III: BCG treatment (Standard of care therapy)Active Control1 Intervention

Bacillus Calmette-Guerrin (BCG) standard of care treatment

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Durvalumab (MEDI4736)

2018

Completed Phase 2

~50

Bacillus Calmette-Guerin (BCG)

2021

Completed Phase 2

~50

0 / 6Eligibility 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, such as Durvalumab and BCG, work by leveraging the body's immune system to fight cancer cells. Durvalumab is a PD-L1 inhibitor that blocks the interaction between PD-L1 on tumor cells and PD-1 on T-cells, thereby preventing the tumor from evading the immune response. BCG, on the other hand, is an intravesical therapy that stimulates a local immune response in the bladder, leading to the activation of immune cells that attack cancer cells. These mechanisms are crucial for bladder cancer patients as they offer a targeted approach to enhance the body's natural defenses against cancer, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.

[Mechanism of action of intravesical BCG. Biological bases and clinical applicability.][The role of immunotherapy in the modern treatment of urothelial carcinoma].