Durvalumab + BCG for Bladder Cancer

(POTOMAC Trial)

Not currently recruiting at 150 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants, Anticancer vaccines

Disqualifiers: Autoimmune disorders, Muscle-invasive cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Induction phase followed by maintenance phase

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness and safety of combining two treatments, Durvalumab (an immunotherapy drug) and BCG (Bacillus Calmette-Guerin, a standard treatment for bladder cancer), for individuals with non-muscle-invasive bladder cancer. The trial compares the standard BCG treatment with the combination of Durvalumab and BCG to determine if the combination is more effective. Individuals with high-risk bladder cancer that has not spread deeper into the muscle or other areas might be suitable candidates, particularly if they have never received BCG treatment or had it more than three years ago. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants the opportunity to contribute to a treatment that could soon become widely available.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but you cannot use immunosuppressive medications within 14 days before starting the trial. Hormonal therapy for non-cancer conditions is allowed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that combining Durvalumab with BCG is generally safe, with side effects similar to those seen when each treatment is used alone. Studies have found that patients can tolerate this combination for up to a year, which reassures those considering joining a trial.

In a previous study, Durvalumab alone was not very effective. However, it has consistently shown safety when used with BCG. Researchers closely monitor treatments using checks like vital signs, lab tests, and heart tests (ECGs) to ensure safety for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Durvalumab and BCG for bladder cancer because it introduces a new way to boost the immune system against cancer cells. While BCG is a well-established treatment that uses weakened bacteria to trigger an immune response, Durvalumab adds another layer by blocking a protein called PD-L1, which cancer cells use to hide from the immune system. This dual approach aims to enhance the overall effectiveness of treatment by not only initiating but also sustaining a robust immune attack on the cancer. This could potentially lead to better outcomes for patients compared to using BCG alone.

What evidence suggests that this trial's treatments could be effective for non-muscle-invasive bladder cancer?

This trial will evaluate the effectiveness of combining Durvalumab with BCG (Bacillus Calmette-Guerin) for non-muscle-invasive bladder cancer. Research has shown that this combination can effectively treat the condition. Specifically, one study found it reduced the risk of cancer recurrence or death by 32% over more than five years and helped patients live longer without the cancer returning. Participants in this trial may receive either the standard BCG treatment alone or the combination of Durvalumab and BCG, which previous studies suggest could be a strong option for patients with this type of bladder cancer. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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).

Inclusion Criteria

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

I had surgery to remove bladder cancer not more than 4 months ago, and all visible cancer was removed.

I have not had radiation therapy for bladder cancer.

Exclusion Criteria

I am not on cancer treatment but can take hormones for other conditions.

I have an autoimmune or inflammatory disorder but it's controlled or I've been stable for the last 5 years.

I had cancer before, but it's either been treated, is low risk, or hasn't come back in over 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Durvalumab + BCG combination therapy or BCG alone as standard of care

Induction phase followed by maintenance phase

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Bacillus Calmette-Guerin (BCG)
• Durvalumab

Trial Overview 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.

How Is the Trial Designed?

Group I: Durvalumab plus BCG (induction only) Experimental Treatment 2 Interventions

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

Group II: Durvalumab plus BCG (induction + maintenance) Experimental Treatment 2 Interventions

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

Group III: BCG treatment (Standard of care therapy) Active Control 1 Intervention

Bacillus Calmette-Guerrin (BCG) standard of care treatment

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In a study of 114 patients with non-muscle invasive bladder cancer, the BCG Danish 1331 strain showed a significantly lower incidence of moderate to severe adverse events compared to the BCG Moscow-I strain, indicating it may be a safer option for treatment.

Both strains demonstrated similar efficacy in terms of 3-year recurrence-free survival (80.0% for Danish 1331 vs. 72.9% for Moscow-I) and progression-free survival (96.5% for Danish 1331 vs. 97.8% for Moscow-I), suggesting that while safety profiles differ, their effectiveness in preventing cancer recurrence is comparable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical bacillus Calmette-Guerin (BCG) in treating non-muscle invasive bladder cancer-analysis of adverse effects and effectiveness of two strains of BCG (Danish 1331 and Moscow-I). Thyavihally, YB., Dev, P., Waigankar, S., et al.[2022]

In a study of 123 patients receiving intravesical BCG treatment for bladder cancer, 95.9% experienced adverse drug reactions, but serious reactions leading to discontinuation were rare, indicating that BCG instillation is generally well tolerated.

The necessity for treatment of adverse effects was significantly influenced by the purpose of the instillation and the BCG dose, suggesting that closer monitoring may be required for patients receiving higher doses (80 mg) for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions of intravesical bacillus Calmette-Guerin instillation and risk factors of the development of adverse drug reactions in superficial cancer and carcinoma in situ of the bladder. Koga, H., Kuroda, M., Kudo, S., et al.[2006]

In a phase II study involving 17 patients with BCG-unresponsive carcinoma in situ of the bladder, durvalumab showed a low complete response rate of only 12% at 6 months, indicating minimal efficacy for this condition.

The treatment was associated with some immune-related adverse events in 41% of patients, and a potential mechanism for resistance was identified through elevated complement activation genes post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Durvalumab for Bacillus Calmette-Guerin (BCG) Unresponsive Urothelial Carcinoma In Situ of the Bladder. Li, R., Sexton, WJ., Dhillon, J., et al.[2023]

In a study of 36 patients undergoing Mycobacterium bovis bacillus Calmette-Guérin (BCG) maintenance therapy for high-risk non-muscle-invasive bladder cancer, 86.7% of those who completed the therapy experienced local adverse reactions, indicating that while the therapy is common, side effects are prevalent.

The analysis suggested that severe adverse reactions, such as gross hematuria and systemic effects during the initial induction therapy, may contribute to a higher rate of discontinuation of the maintenance therapy, highlighting the importance of monitoring and managing these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions related to treatment compliance during BCG maintenance therapy for non-muscle-invasive bladder cancer. Miyazaki, J., Hinotsu, S., Ishizuka, N., et al.[2013]

Immunotherapy with Bacillus Calmette Guerin (BCG) is an effective long-term treatment for high-grade superficial bladder cancer, with a 35% recurrence rate and 74% of patients alive after a median follow-up of 71 months.

The study suggests that BCG therapy is a viable conservative option, as only 9% of patients required cystectomy, indicating that aggressive surgical intervention may not be necessary as a first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High grade superficial (G3t1) transitional cell carcinoma of the bladder treated with intravesical Bacillus Calmette-Guerin (BCG). Pansadoro, V., Emiliozzi, P., depaula, F., et al.[2006]

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[2022]

The combination of intravesical Bacillus Calmette-Guérin (BCG) and systemic pembrolizumab was found to be safe in a phase I trial involving 18 patients with high-grade non-muscle-invasive bladder cancer, with 69% of treated patients showing no evidence of disease after 3 months.

Despite some treatment-related adverse events, including one severe case of adrenal insufficiency and several grade 3 adverse events, the overall safety profile supports further investigation, leading to the initiation of a phase III trial to evaluate the efficacy of this combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of intravesical Bacillus Calmette-Guérin combined with intravenous pembrolizumab in recurrent or persistent high-grade non-muscle-invasive bladder cancer after previous Bacillus Calmette-Guérin treatment. Alanee, S., Sana, S., El-Zawahry, A., et al.[2022]

This study aims to systematically evaluate the efficacy and safety of Bacillus Calmette-Guerin (BCG) treatment for bladder cancer by reviewing high-quality trials from various databases, ensuring a comprehensive analysis.

The findings will provide crucial evidence to determine the effectiveness of BCG in treating bladder cancer, potentially influencing treatment decisions for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Bacillus Calmette-Guerin for bladder cancer: A protocol of systematic review. Zhang, ZH., Yin, L., Zhang, LL., et al.[2023]

Citations

1. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/IMFINZI-durvalumab-regimen-reduced-the-risk-of-disease-recurrence-or-death-by-32-percent-in-high-risk-non-muscle-invasive-bladder-cancer-in-the-POTOMAC-Phase-III-trial.html

IMFINZI® (durvalumab) regimen reduced the risk of ... With a median follow-up of more than five years (60.7 months), the IMFINZI regimen showed a 32% reduction in the risk of high-risk disease ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12065394/

A Phase 2 Study of Durvalumab for Bacillus Calmette- ... Conclusions: Durvalumab monotherapy conferred minimal efficacy in treating BCG-unresponsive CIS of the bladder, with 6mo complete response of 12%. Complement ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03528694

Study Details | NCT03528694 | Assessment of Efficacy and ... Patients will be randomized in a 1:1:1 ratio to receive treatment with Durvalumab + BCG combination therapies, or Standard of Care (SoC) therapy. Official Title.

4. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)02015-X/fulltext?rss=yes

Front-line durvalumab and BCG in the treatment of non- ... Grade 3–4 treatment-related adverse events occurred in 71 (21%) of 336 patients in the durvalumab plus BCG induction and maintenance group, 52 ( ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0140673625018975

Durvalumab in combination with BCG for BCG-naive, high- ... The final analysis of the POTOMAC study showed a statistically significant and clinically meaningful improvement in disease-free survival with ...

6. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)01897-5/abstract

Durvalumab in combination with BCG for BCG-naive, high- ... The combination had a manageable safety profile, consistent with that of the individual therapies. These results support 1 year of durvalumab in ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.778

Feasibility and safety results from RAD-IO Recent phase 3 results with peri-operative durvalumab show a 25% reduction in the risk of death compared to standard of care. Methods: RADIO is ...

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)04349-7/fulltext

273MO DURANCE: A phase Ib/II study to assess the safety ... Co-administration of durvalumab and S-488210/S-488211 vaccine is safe and well tolerated. The encouraging response rate at the first cystoscopy assessment ...