Durvalumab +/- Tremelimumab for Bladder Cancer

Not currently recruiting at 247 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Autoimmune disorders, Brain metastases, Active infection, 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: 11

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for individuals with stage IV bladder cancer who have not received first-line chemotherapy. Researchers aim to determine whether Durvalumab (an immunotherapy drug) alone or combined with Tremelimumab (another immunotherapy drug) is more effective than standard chemotherapy options. The trial includes three groups: one receiving Durvalumab, another receiving Durvalumab with Tremelimumab, and a third receiving standard chemotherapy. Suitable candidates for this trial are those with stage IV bladder cancer who have not yet begun chemotherapy treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants access to potentially groundbreaking treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use immunosuppressive medications within 14 days before starting the trial. Some exceptions include certain steroids and premedications for allergies.

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

Research has shown that durvalumab generally has a manageable safety profile. In studies, 30% of patients experienced serious side effects when combined with certain chemotherapy drugs. Common issues included immune system problems, though these were infrequent.

For the combination of durvalumab and tremelimumab, research found that serious side effects occurred in about 31% of patients. The most common issues were diarrhea and kidney problems, each affecting around 6% of participants. Overall, this combination was generally well tolerated.

These numbers can help prospective trial participants understand the frequency of serious side effects. It's important to weigh these risks against potential benefits. Always consult a healthcare provider for personalized advice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard chemotherapy options like carboplatin, cisplatin, and gemcitabine, which attack cancer cells directly, the investigational treatments involving Durvalumab and the combination of Durvalumab with Tremelimumab offer a different approach. These drugs are part of a class called immune checkpoint inhibitors. They work by blocking proteins that prevent the immune system from attacking cancer cells, essentially enabling the body's own defenses to fight the cancer more effectively. Researchers are excited about these treatments because they have the potential to enhance the immune response against bladder cancer, possibly leading to more durable and long-lasting effects than traditional chemotherapy.

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

Research has shown that durvalumab, which participants in this trial may receive as monotherapy, may help treat bladder cancer. In patients with PD-L1-positive urothelial bladder cancer, it has effectively slowed the disease. Additionally, another group in this trial will receive a combination of durvalumab with tremelimumab. This combination has shown strong results in other studies, helping to preserve the bladder. Early results suggest that this combination can be safe and effective for some patients with muscle-invasive bladder cancer. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with Stage IV bladder cancer who haven't had first-line chemotherapy. They must know their tumor PD-L1 status and can be eligible or ineligible for cisplatin-based chemo due to certain health conditions. People with prior immune therapy, autoimmune/inflammatory disorders, brain metastases not stable off steroids, active infections like TB/HIV, recent live vaccines, or current immunosuppressants (with some exceptions) cannot join.

Inclusion Criteria

My tumor's PD-L1 status has been confirmed by a lab test.

I have Stage IV bladder cancer that hasn't been treated with first-line chemotherapy.

I am either eligible or not for cisplatin chemotherapy based on specific health conditions.

Exclusion Criteria

I have previously received immunotherapy or vaccines for cancer, but not within the last 28 days.

My brain or spinal cord cancer is stable, and I haven't taken steroids for over 2 weeks.

I do not have active infections like TB, hepatitis B, C, or HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MEDI4736 (Durvalumab) monotherapy, MEDI4736 (Durvalumab) in combination with Tremelimumab, or standard of care chemotherapy until disease progression or unacceptable toxicity

Up to 2 years

Every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

At follow-up Month 3

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Gemcitabine
• MEDI4736 (Durvalumab)
• Tremelimumab

Trial Overview The study tests Durvalumab alone or combined with Tremelimumab against standard chemo drugs (Gemcitabine with Cisplatin or Carboplatin). It's a Phase III trial where patients are randomly assigned to one of these treatments to compare effectiveness as a first-line treatment in advanced bladder cancer.

How Is the Trial Designed?

Group I: Monotherapy Experimental Treatment 1 Intervention

MEDI4736 (Durvalumab)

Group II: Combination Therapy Experimental Treatment 2 Interventions

MEDI4736 (Durvalumab) + Tremelimumab

Group III: Standard of Care Active Control 3 Interventions

Standard of Care Chemotherapy Treatment

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

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

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

In a phase I trial involving Japanese patients with advanced cancer, tremelimumab was found to be safe and well-tolerated, with no dose-limiting toxicities observed in the initial dosing phase, although 75% of patients reported treatment-related adverse events.

When combined with durvalumab, tremelimumab showed a manageable safety profile, with only two instances of serious adverse events (Grade 4 myasthenia gravis and hyperglycemia), indicating that the combination therapy can be administered with careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Tremelimumab Monotherapy or in Combination With Durvalumab in Japanese Patients With Advanced Solid Tumors or Malignant Mesothelioma. Fujiwara, Y., Takahashi, Y., Okada, M., et al.[2022]

Urothelial carcinoma, the most common urological cancer, is primarily treated with Bacillus Calmette-Guerin (BCG) immunotherapy for superficial cases and cisplatin-based chemotherapy for metastatic disease, with vinflunine as the standard second-line option in Europe.

Novel PD-1/PD-L1 inhibitors like atezolizumab, nivolumab, and pembrolizumab have shown promise in treating bladder cancer, particularly for patients who cannot tolerate cisplatin, and are generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. Büchler, T.[2019]

In a phase 3 trial involving 1032 patients with metastatic urothelial carcinoma, durvalumab alone showed a median overall survival of 14.4 months in patients with high PD-L1 expression, compared to 12.1 months with standard chemotherapy, although this difference was not statistically significant.

The combination of durvalumab and tremelimumab resulted in a median overall survival of 15.1 months in the overall patient population, compared to 12.1 months for chemotherapy, but again, this did not meet the primary endpoint for significance, highlighting the need for further research into which patients may benefit from these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial. Powles, T., van der Heijden, MS., Castellano, D., et al.[2021]

In the CASPIAN study involving 805 patients with extensive-stage small-cell lung cancer (ES-SCLC), the combination of durvalumab and platinum-etoposide significantly improved overall survival compared to platinum-etoposide alone, with a median survival of 12.9 months versus 10.5 months.

However, adding tremelimumab to durvalumab and platinum-etoposide did not provide a significant survival benefit, indicating that durvalumab plus platinum-etoposide should be considered the new standard of care for first-line treatment of ES-SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Goldman, JW., Dvorkin, M., Chen, Y., et al.[2021]

Citations

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

Feasibility and safety results from RAD-IO A multi-stage trial of durvalumab (Medi4736) with chemoradiotherapy with 5-fluorouracil and mitomycin C in patients with muscle-invasive bladder cancer.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27269937/

Safety and Efficacy of Durvalumab (MEDI4736), an ... - PubMed Conclusion: Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1-positive patients with UBC ...

3. imfinzihcp.com imfinzihcp.com/bladder-cancer/muscle-invasive/efficacy.html

Efficacy and Clinical Trial Data for IMFINZI® (durvalumab) Healthcare professionals can review efficacy data for IMFINZI and clinical trial results in FDA-approved indications.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03528694

Study Details | NCT03528694 | Assessment of Efficacy and ... The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of time to muscle invasive bladder cancer and/or metastatic ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40755829/

Cost-effectiveness of perioperative durvalumab plus ... In conclusion, adding durvalumab to chemotherapy appears to be a cost-effective option for treating operable bladder cancer, offering better ...

6. urotoday.com urotoday.com/conference-highlights/eau-2025/eau-2025-bladder-cancer/159119-eau-2025-niagara-surgical-outcomes-and-neoadjuvant-safety-with-perioperative-durvalumab-for-muscle-invasive-bladder-cancer.html

EAU 2025: NIAGARA: Surgical Outcomes and ... EAU 2025 surgical outcomes and neoadjuvant safety with perioperative durvalumab for muscle-invasive bladder cancer, NIAGARA trial, ...