Avelumab Combinations for Bladder Cancer

Not currently recruiting at 148 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of avelumab (also known as MSB0010718C or Bavencio), both alone and with other drugs, for treating bladder cancer. Researchers focus on using these treatments as maintenance therapy to prevent cancer from worsening after initial treatment. Participants may qualify if they have completed chemotherapy for advanced bladder cancer and their cancer has not progressed. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

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.

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

Research has shown that avelumab, whether used alone or with other drugs, is generally well-tolerated. In various studies, patients with advanced bladder cancer continued treatment without severe side effects. Avelumab has consistently demonstrated long-term safety, especially for bladder cancer patients.

For the combination of avelumab and sacituzumab govitecan, safety data appears promising. Trials have indicated that this combination is manageable in treating advanced cancer. Sacituzumab govitecan is effective against cancer and works well with avelumab.

The combination of avelumab and NKTR-255 remains under study, but it benefits from avelumab's established safety. NKTR-255 has shown potential in improving certain immune conditions in other cases, suggesting it might be safe with avelumab.

Lastly, the combination of avelumab and M6223 has been tested. Both M6223 alone and with avelumab have demonstrated a manageable safety profile, with expected and controllable side effects.

In summary, these treatments have shown promising safety results in previous studies, making them potential options for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments being explored in this bladder cancer trial because they introduce unique mechanisms to combat the disease. Avelumab, already known for its role as an immunotherapy, is being combined with other promising agents to enhance its effectiveness. Sacituzumab Govitecan is an antibody-drug conjugate that delivers chemotherapy directly to cancer cells, potentially increasing precision and reducing side effects. NKTR-255 is designed to boost the immune system by stimulating natural killer cells and T cells, offering a fresh angle compared to traditional treatments. M6223, another novel agent, works by targeting specific proteins that regulate immune response, aiming to improve outcomes by enhancing the body's natural defenses against cancer. Each of these combinations represents a step forward in personalizing and intensifying treatment for bladder cancer.

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

Research has shown that avelumab, which participants in this trial may receive, holds promise for treating bladder cancer. Studies indicate that patients using avelumab as maintenance therapy have lived longer and experienced more time without disease progression. In this trial, some participants will receive avelumab alone, while others will receive it in combination with other treatments. When combined with sacituzumab govitecan, more patients respond positively compared to avelumab alone. Adding NKTR-255 to avelumab aims to strengthen the immune system, which has proven beneficial in other cancers. Early results for M6223 with avelumab suggest safety and potential effectiveness, but further research is needed. Overall, these treatments are being actively studied in this trial to find the best ways to improve outcomes for bladder cancer patients. ^{1 2 6 7 8}

Who Is on the Research Team?

Medical Responsible

Principal Investigator

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

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]

Citations

1. bavencio.com bavencio.com/en_US/patients-and-caregivers/uc-home/about-bavencio/study-results.html

Study Results | BAVENCIO® (avelumab) Efficacy BAVENCIO showed consistent results when the study kept track of patients for over 3 years. BAVENCIO® Long Term Data. BAVENCIO®-Long-Term-Data.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11988210/

Real-world avelumab first-line maintenance in advanced ... In this study, the researchers looked at real‑world evidence in people with advanced bladder cancer who received avelumab maintenance after ...

3. bavencio.com bavencio.com/en_US/hcp/uc-home/efficacy.html

JAVELIN Bladder Trial Efficacy | BAVENCIO® (avelumab) ... LONG-TERM ANALYSIS (3+ years): Consistent OS results were observed · Median follow-up: 38.0 months (95% CI: 36.1, 40.5) in the BAVENCIO + BSC arm; 39.6 months ( ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2588931124002232

Real-world Study of Avelumab First-line Maintenance ... Overall, results were consistent with those seen in a previous clinical trial, and on average, people treated with avelumab maintenance lived for 26.5 mo from ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11884485/

Outcomes of Avelumab Treatment in Advanced Urothelial ... For a 10% reduction in serious adverse events, mild to moderate nausea, or skin reactions, patients would accept reductions in the ORR of 5.5%, ...

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa2002788

Avelumab Maintenance Therapy for Advanced or ... In patients with PD-L1–negative tumors, the median progression-free survival was 3.0 months (95% CI, 2.0 to 3.7) in the avelumab group and 1.9 ...

7. emdserono.com emdserono.com/us-en/company/news/press-releases/new-analyses-reinforce-survival-benefit-of-bavencio-first-line-maintenance-treatment-in-patients-with-advanced-urothelial-carcinoma-13-02-2023.html

New Analyses Reinforce Survival Benefit of BAVENCIO In the overall population, patients who received BAVENCIO plus BSC had a median OS of 29.7 months (95% CI, 25.2-34.0) as measured from the start ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39448350/

Real-world Study of Avelumab First-line Maintenance ... A French real-world study, called AVENANCE, looked at avelumab maintenance treatment in people with advanced urothelial cancer whose tumor disappeared, shrank, ...