Durvalumab + Tremelimumab for Bladder Cancer

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunotherapy, Corticosteroids

Disqualifiers: Autoimmune disease, HIV/AIDS, Hepatitis B/C, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

54 Participants Needed

Trial Summary

What is the purpose of this trial?

This pilot phase I trial studies the side effects of durvalumab and tremelimumab in treating patients with muscle-invasive, high-risk urothelial cancer that cannot be treated with cisplatin-based therapy before surgery. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment. Non-cancer-related medications like insulin for diabetes are allowed.

What data supports the effectiveness of the drug combination Durvalumab and Tremelimumab for bladder cancer?

Durvalumab has been approved for treating advanced bladder cancer after chemotherapy, showing it can help the immune system fight cancer. Tremelimumab, when combined with Durvalumab, has been approved for other cancers like liver and lung cancer, suggesting potential effectiveness in similar conditions. ^{1 2 3 4 5}

Is the combination of Durvalumab and Tremelimumab generally safe for humans?

The combination of Durvalumab and Tremelimumab has been studied in various cancers and shows a tolerable safety profile, though it may lead to more severe side effects like reduced appetite and diarrhea compared to Durvalumab alone. ^{1 3 6 7 8}

What makes the drug combination of Durvalumab and Tremelimumab unique for bladder cancer treatment?

The combination of Durvalumab and Tremelimumab is unique because it uses two different monoclonal antibodies to enhance the immune system's ability to fight cancer: Durvalumab blocks PD-L1, and Tremelimumab blocks CTLA-4, both of which help boost T-cell responses against cancer cells. This approach is particularly novel for patients with bladder cancer who have limited options after failing platinum-based chemotherapy. ^{1 2 3 7 8}

Research Team

Jianjun Gao

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with muscle-invasive, high-risk urothelial cancer who can't have cisplatin-based therapy. They need proof of cancer from a specific bladder tissue resection, good organ and marrow function, no prior immunotherapy, an ECOG status of 0-1, and must agree to use effective contraception if applicable. Exclusions include HIV/AIDS, recent vaccines or surgeries, pregnancy, uncontrolled illnesses, allergies to study drugs, other ongoing cancer treatments or trials (with exceptions), certain autoimmune diseases or conditions.

Inclusion Criteria

I use effective birth control because I can still have children.

I am a man who can father children and will use effective birth control.

I have a mild or well-controlled autoimmune condition.

Exclusion Criteria

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

I haven't had major surgery in the last 28 days or am still recovering from one.

You have received any experimental cancer treatment within the 28 days before starting durvalumab and tremelimumab.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive tremelimumab and durvalumab intravenously on day 1 of weeks 1 and 4

4 weeks

2 visits (in-person)

Surgery

Patients undergo cystectomy with pelvic lymph node dissection surgery 4-6 weeks after the last infusion

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

1 visit at 90 days, then every 3 months

Treatment Details

Interventions

• Durvalumab
• Therapeutic Conventional Surgery
• Tremelimumab

Trial Overview The trial tests durvalumab and tremelimumab's safety in treating urothelial cancers that are ineligible for cisplatin before surgery. These monoclonal antibodies may boost the immune system to stop tumor growth and spread. It's a phase I pilot study focusing on side effects as well as potential efficacy.

Participant Groups

Group I: Treatment (tremelimumab, durvalumab) Experimental Treatment 3 Interventions

Patients receive tremelimumab IV over 1 hour and durvalumab IV over 1 hour on day 1 of weeks 1 and 4. Beginning 4-6 weeks after the last infusion, patients undergo cystectomy with pelvic lymph node dissection surgery.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

Tremelimumab, a CTLA-4 blocking antibody, was approved in the USA in October 2022 for treating unresectable hepatocellular carcinoma (uHCC) in combination with durvalumab, marking a significant advancement in cancer therapy.

In November 2022, tremelimumab was also approved for metastatic non-small cell lung cancer (mNSCLC) when combined with durvalumab and platinum-based chemotherapy, indicating its broad potential in treating various malignant tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tremelimumab: First Approval. Keam, SJ.[2023]

In the phase 3 MYSTIC study involving 488 treatment-naïve patients with metastatic non-small-cell lung cancer, durvalumab alone or in combination with tremelimumab showed significant improvements in patient-reported outcomes (PROs) compared to chemotherapy, particularly in reducing fatigue and appetite loss.

Patients receiving durvalumab-containing treatments experienced a longer time to deterioration in quality of life and physical functioning, indicating that these treatments may help maintain better overall well-being without negatively impacting quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non-Small-Cell Lung Cancer (MYSTIC). Garon, EB., Cho, BC., Reinmuth, N., et al.[2022]

In the phase 3 POSEIDON study involving 1013 treatment-naïve patients with metastatic non-small-cell lung cancer (NSCLC), the combination of tremelimumab, durvalumab, and chemotherapy significantly improved overall survival and progression-free survival compared to chemotherapy alone.

Patients receiving the combination treatment also experienced a longer time to deterioration in quality of life and various symptoms, indicating better overall health status compared to those on chemotherapy, supporting its use as a first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON). Garon, EB., Cho, BC., Luft, A., et al.[2023]

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]

The combination of durvalumab and tremelimumab showed improved disease control rates in patients with head and neck squamous cell carcinoma compared to tremelimumab alone, indicating its potential efficacy in this cancer type.

The combination therapy had a tolerable safety profile, with no significant increase in treatment-related adverse events compared to monotherapy, suggesting it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab and tremelimumab combination therapy versus durvalumab or tremelimumab monotherapy for patients with solid tumors: A systematic review and meta-analysis. Wang, BC., Li, PC., Fan, JQ., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Tolerability of Tremelimumab in Locally Advanced or Metastatic Urothelial Carcinoma Patients Who Have Failed First-Line Platinum-Based Chemotherapy. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Tremelimumab: First Approval. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non-Small-Cell Lung Cancer (MYSTIC). [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON). [2023]

6. Switzerland 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. [2023]

7. England 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. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Durvalumab and tremelimumab combination therapy versus durvalumab or tremelimumab monotherapy for patients with solid tumors: A systematic review and meta-analysis. [2022]