Avelumab Combinations for Bladder Cancer

Recruiting at 114 trial locations

Overseen By Communication Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: EMD Serono Research & Development Institute, Inc.

Must not be taking: Immunotherapy, Interleukin, Interferon, others

Disqualifiers: Active infection, Hypersensitivity, others

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

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

256 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the safety and efficacy of avelumab in combination with other anti-tumor agents as a maintenance treatment in participants with bladder cancer.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does exclude participants who have had certain immunotherapies or systemic therapies recently, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Avelumab for bladder cancer?

Research shows that Avelumab, when used as a maintenance therapy after initial chemotherapy, can help extend the time patients with advanced bladder cancer live without the disease getting worse. It has become a standard treatment option for these patients, especially those who cannot undergo certain types of chemotherapy. ^{1 2 3 4 5}

Is the combination of Avelumab and other drugs safe for treating bladder cancer?

Avelumab, used alone or in combination with other drugs like sacituzumab govitecan, has shown a promising safety profile in treating advanced bladder cancer. Common side effects include tiredness, low white blood cell count, anemia (low red blood cell count), muscle pain, reduced appetite, and nausea, but it is generally well-tolerated. ^{2 5 6 7 8}

How does the drug avelumab differ from other treatments for bladder cancer?

Avelumab is unique because it is an anti-PD-L1 antibody that helps the immune system attack cancer cells, and it is used as a maintenance therapy after initial chemotherapy to prolong survival in patients with advanced bladder cancer. Unlike traditional chemotherapy, avelumab specifically targets the PD-L1 protein, making it a valuable option for patients who cannot tolerate cisplatin-based treatments. ^{2 5 9 10 11}

Research Team

Medical Responsible

Principal Investigator

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Eligibility Criteria

This trial is for adults with advanced bladder cancer who've completed initial chemotherapy without disease progression. They must have a good performance status, meaning they're relatively active and can care for themselves. Participants need proper organ function and an expected lifespan of at least 3 months. Those previously treated with certain immunotherapies or systemic therapies within the last year are excluded.

Inclusion Criteria

My blood, liver, and kidney functions meet the required levels.

My cancer did not worsen after 4-6 rounds of initial chemotherapy.

My bladder cancer cannot be removed by surgery and has spread.

Exclusion Criteria

I had treatment before or after surgery less than a year ago.

I have an infection that needed treatment within the last 48 hours.

Participants with known prior or suspected hypersensitivity to study drugs or any component in their formulations

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive avelumab in combination with other anti-tumor agents as a maintenance treatment

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Avelumab
• M6223
• NKTR-255
• Sacituzumab Govitecan

Trial Overview The study tests the safety and effectiveness of Avelumab in combination with other anti-cancer drugs as maintenance therapy for bladder cancer patients post-chemotherapy. It aims to see if these combinations help control the disease better than current treatments.

Participant Groups

Group I: Group D: Avelumab + NKTR-255 Experimental Treatment 2 Interventions

Group II: Group C: Avelumab + M6223 Experimental Treatment 2 Interventions

Group III: Group B: Avelumab + Sacituzumab Govitecan Experimental Treatment 2 Interventions

Group IV: Group A: Avelumab Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

EMD Serono Research & Development Institute, Inc.

Lead Sponsor

Trials

86

Recruited

22,700+

Miguel Fernández Alcalde

EMD Serono Research & Development Institute, Inc.

Chief Executive Officer

Bachelor’s Degree in Pharmacy from the University Complutense in Madrid, MBA from the University of Alcalá de Henares, Master’s Degree in Management from IESE Business School

Danny Bar-Zohar

EMD Serono Research & Development Institute, Inc.

Chief Medical Officer since 2022

MD

Merck KGaA, Darmstadt, Germany; Gilead Sciences; Nektar Therapeutics

Collaborator

Trials

1

Recruited

260+

Findings from Research

In a study of 204 patients with advanced urothelial carcinoma, those receiving maintenance avelumab therapy showed longer overall survival compared to those receiving second-line pembrolizumab or cytotoxic chemotherapy, although progression-free survival was not significantly different.

Patients who started maintenance avelumab therapy within 6 weeks of completing first-line chemotherapy had a higher disease control rate (77%) compared to those who waited longer, suggesting that early initiation of avelumab may enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switch-maintenance avelumab immunotherapy following first-line chemotherapy for patients with advanced, unresectable or metastatic urothelial carcinoma: the first Japanese real-world evidence from a multicenter study. Miyake, M., Shimizu, T., Oda, Y., et al.[2023]

Avelumab, a PD-L1 inhibitor, has been established as a new standard of care for patients with advanced or metastatic urothelial carcinoma (UC) following platinum-based chemotherapy, based on results from the JAVELIN bladder 100 trial.

The use of maintenance avelumab after initial chemotherapy has shown promise in restoring T cell responses against tumors, indicating a potential improvement in treatment outcomes for UC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab in locally advanced or metastatic urothelial carcinoma. Jackson-Spence, F., Szabados, B., Toms, C., et al.[2022]

In a study involving 71 patients with metastatic urothelial cancer (mUC) who were ineligible for cisplatin-based chemotherapy, avelumab demonstrated a median overall survival of 10 months, with 43% of patients alive at one year, indicating its efficacy as a first-line treatment option.

Avelumab was found to be safe, with adverse events occurring in 49.3% of patients, but no treatment-related deaths were reported, suggesting it is a tolerable option for patients who cannot receive traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line avelumab for patients with PD-L1-positive metastatic or locally advanced urothelial cancer who are unfit for cisplatin. Iacovelli, R., Ciccarese, C., Brunelli, 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]

Avelumab demonstrated antitumor activity in patients with platinum-refractory metastatic urothelial carcinoma, achieving a complete or partial response in 17% of treated patients, including 6% with complete responses.

The safety profile of avelumab was manageable, with most treatment-related adverse events being mild (grade 1-2), although there were serious adverse events in 8% of patients, including one treatment-related death from pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. Patel, MR., Ellerton, J., Infante, JR., et al.[2022]

In a phase I trial involving 23 patients with metastatic urothelial carcinoma, the combination of sacituzumab govitecan (SG) and enfortumab vedotin (EV) demonstrated a high objective response rate of 70%, with three patients achieving complete responses.

The study identified a safe dose for further testing, with 78% of patients experiencing grade ≥3 adverse events, indicating that while the treatment is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Double Antibody Drug Conjugate (DAD) phase I trial: sacituzumab govitecan plus enfortumab vedotin for metastatic urothelial carcinoma. McGregor, BA., Sonpavde, GP., Kwak, L., et al.[2023]

Avelumab maintenance therapy is considered cost-effective for treating advanced or metastatic urothelial cancer (mUC) in the United States, with incremental cost-effectiveness ratios (ICERs) of $38,369.50 per QALY for the overall population and $16,150.29 per QALY for the PD-L1-positive population.

In contrast, avelumab was not deemed cost-effective in China, with ICERs of $241,610.25 and $100,528.29 per QALY for the overall and PD-L1-positive populations, respectively, exceeding the local willingness to pay threshold.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Avelumab Maintenance Therapy Plus Best Supportive Care vs. Best Supportive Care Alone for Advanced or Metastatic Urothelial Carcinoma. Xie, Q., Zheng, H., Chen, Y., et al.[2022]

Avelumab maintenance therapy after platinum-based chemotherapy in advanced urothelial carcinoma significantly improves overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), especially in patients with PD-L1 positive tumors, compared to those receiving best supportive care.

While avelumab is effective, it is associated with a high rate of treatment-related adverse events (TRAEs) in 86.7% of patients, with 32.4% experiencing severe adverse events, indicating the need for careful patient monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Evaluation of Avelumab in the Treatment of Advanced Urothelial Carcinoma: Focus on Patient Selection and Outcomes. Ten Eyck, JE., Kahlon, N., Masih, S., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Switch-maintenance avelumab immunotherapy following first-line chemotherapy for patients with advanced, unresectable or metastatic urothelial carcinoma: the first Japanese real-world evidence from a multicenter study. [2023]

2. England pubmed.ncbi.nlm.nih.gov

The JAVELIN Bladder Medley trial: avelumab-based combinations as first-line maintenance in advanced urothelial carcinoma. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Avelumab in locally advanced or metastatic urothelial carcinoma. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Avelumab First-line Maintenance for Advanced Urothelial Carcinoma: Analysis from JAVELIN Bladder 100 by Duration of First-line Chemotherapy and Interval Before Maintenance. [2023]

5. England pubmed.ncbi.nlm.nih.gov

First-line avelumab for patients with PD-L1-positive metastatic or locally advanced urothelial cancer who are unfit for cisplatin. [2022]

6. Czech Republic pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. [2022]

8. England pubmed.ncbi.nlm.nih.gov

The Double Antibody Drug Conjugate (DAD) phase I trial: sacituzumab govitecan plus enfortumab vedotin for metastatic urothelial carcinoma. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Avelumab Maintenance Therapy Plus Best Supportive Care vs. Best Supportive Care Alone for Advanced or Metastatic Urothelial Carcinoma. [2022]

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

Clinical Evaluation of Avelumab in the Treatment of Advanced Urothelial Carcinoma: Focus on Patient Selection and Outcomes. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Patient-reported Outcomes from JAVELIN Bladder 100: Avelumab First-line Maintenance Plus Best Supportive Care Versus Best Supportive Care Alone for Advanced Urothelial Carcinoma. [2023]