Avelumab + Radiation for Bladder Cancer

No longer recruiting at 1 trial location

Overseen By James Parisi

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Immunosuppressants

Disqualifiers: Prior therapy, Metastatic disease, Cardiovascular, Autoimmune, 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: 6

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for muscle-invasive bladder cancer by adding the immunotherapy drug Avelumab to standard radiation treatment. The goal is to determine if this combination controls or shrinks tumors more effectively than radiation alone. Suitable candidates for this trial include individuals with bladder cancer that has spread into the muscle layer and who cannot take common chemotherapy drugs due to medical reasons such as kidney issues or hearing loss. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to potentially benefit from an innovative approach.

Do I have to stop taking my current medications for the trial?

The trial requires you to stop any current chemotherapy, biologic, or hormonal therapy for cancer treatment. You also cannot use immunosuppressive medications, except for certain low-dose steroids or specific premedications. The protocol does not specify other medications, but you should discuss your current medications with the trial team.

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

Research shows that avelumab, the immunotherapy drug in this study, has been well-tolerated by patients with bladder cancer. In one study, participants who took avelumab lived for nearly 30 months on average, indicating its relative safety over time. Another study found avelumab safe as a maintenance treatment, with many participants continuing without serious problems for about six months.

Regarding radiation therapy, studies indicate it is generally safe for treating bladder cancer. Many patients experienced symptom improvement, such as reduced bleeding in urine. Research also shows that radiation therapy is safe for those unable to undergo standard chemotherapy, offering a viable option without severe side effects.

Overall, previous research has shown both avelumab and radiation therapy to be safe, with many patients handling these treatments well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatment options for bladder cancer, which often include chemotherapy and surgery, avelumab combined with radiation offers a unique approach. Avelumab is an immunotherapy drug that works by blocking the PD-L1 protein, helping the immune system recognize and attack cancer cells more effectively. This mechanism is different from traditional treatments, which focus on directly killing cancer cells rather than boosting the body's immune response. Researchers are excited about this combination because it has the potential to enhance the effectiveness of radiation therapy, possibly leading to better outcomes for patients with bladder cancer.

What evidence suggests that Avelumab combined with radiation might be an effective treatment for bladder cancer?

In this trial, participants will receive a combination of Avelumab and bladder-directed radiation. Studies have shown that Avelumab, used as a maintenance treatment, is effective for advanced bladder cancer. Patients taking Avelumab tend to live longer, with some research indicating an average survival of about 21 to 26 months. Radiation therapy for bladder cancer also shows promise, as many patients experience symptom improvement and increased survival compared to those receiving only supportive care. Combining Avelumab and radiation might enhance treatment effectiveness, as both have independently improved outcomes. Early research suggests that this combination could help the body fight cancer more effectively. ^{1 6 7 8 9}

Who Is on the Research Team?

Kent Mouw, MD, PhD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

Adults with muscle-invasive bladder cancer who can't receive cisplatin chemotherapy due to certain health issues or personal choice. They must have normal organ/marrow function, not be pregnant, agree to use contraception if there's a risk of conception, and have no history of severe allergies to monoclonal antibodies or other exclusion criteria like active infections.

Inclusion Criteria

Ability to understand and willingness to sign a written informed consent document

My bladder cancer has spread into the muscle layer.

I can start the study treatment within 1-8 weeks after my last bladder tumor surgery.

Exclusion Criteria

I have not had major surgery in the last 30 days, except for TURBT.

I am not currently on any cancer treatments like chemotherapy.

I have received IV therapy for bladder cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Avelumab every 2 weeks for 6 doses and bladder-directed radiation

12 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Long-term follow-up

Participants' overall survival, progression-free survival, and quality of life are monitored

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Avelumab
• Radiation

Trial Overview The trial is testing the combination of Avelumab (an immunotherapy drug) with standard radiation therapy for treating muscle-invasive urothelial carcinoma. The goal is to see if adding Avelumab improves treatment outcomes compared to radiation alone.

How Is the Trial Designed?

Group I: Avelumab and Bladder-Directed Radiation Experimental Treatment 2 Interventions

* Avelumab will be administered every 2 weeks intravenously for 6 doses unless there is unacceptable toxicity * Two radiation dose regimens are allowed, and the regimen selected is at the discretion of the treating radiation oncologist

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

Approved in European Union as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in United States as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in Japan as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

EMD Serono

Industry Sponsor

Trials

147

Recruited

27,800+

Dr. Shepard

EMD Serono

Chief Medical Officer since 2021

MD from University of Cincinnati Medical School, Fellowships in Hematology and Oncology at University of Chicago Hospitals and Clinics

Miguel Fernández Alcalde

EMD Serono

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

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

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]

Avelumab, an anti-PD-L1 antibody, was well tolerated in 44 patients with refractory metastatic urothelial carcinoma, showing a low incidence of severe treatment-related adverse events (6.8%).

The treatment resulted in a confirmed objective response rate of 18.2%, with a median overall survival of 13.7 months, indicating its potential effectiveness in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab, an Anti-Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study. Apolo, AB., Infante, JR., Balmanoukian, A., 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, an anti-PD-L1 antibody, demonstrated prolonged efficacy in patients with platinum-treated advanced/metastatic urothelial carcinoma, with a confirmed overall response rate of 16.5% and a median overall survival of 7.0 months after a median follow-up of 31.9 months.

The treatment was particularly effective in high-risk subgroups, such as elderly patients and those with renal insufficiency, and early response to treatment (within 3 months) was associated with significantly longer overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab as second-line therapy for metastatic, platinum-treated urothelial carcinoma in the phase Ib JAVELIN Solid Tumor study: 2-year updated efficacy and safety analysis. Apolo, AB., Ellerton, JA., Infante, JR., et al.[2021]

In a phase 2 study involving 45 patients with invasive bladder cancer, the combination of radiation therapy and atezolizumab resulted in a high pathologic complete response (pCR) rate of 84.4%, particularly in older patients and those with high PD-L1 expression.

The treatment was associated with acceptable toxicity, with 93.3% of patients experiencing adverse events, mostly mild to moderate, and only 13.3% experiencing grade 3 adverse events, indicating that this approach could be a viable bladder-preserving option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial. Kimura, T., Ishikawa, H., Nagumo, Y., et al.[2023]

Avelumab, an immune checkpoint inhibitor, demonstrated a 14.18% objective response rate in 3935 cancer patients across 21 trials, showing more tumor responses compared to conventional treatments.

The treatment was associated with a lower incidence of adverse events, with only 14.44% experiencing high-grade treatment-related adverse events, indicating that avelumab has an active anti-tumor effect with manageable safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety profile of avelumab monotherapy. Zhao, B., Gao, M., Zhao, H., et al.[2021]

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]

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/PMC12572945/

Real‐World Outcomes of Avelumab Maintenance Therapy ... Findings demonstrate the acceptable safety, tolerability, and effectiveness of avelumab maintenance, consistent with data from JAVELIN Bladder ...

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. urotoday.com urotoday.com/conference-highlights/asco-gu-2024/asco-gu-2024-bladder-cancer/149394-asco-gu-2024-updated-results-from-avenance-real-world-effectiveness-of-avelumab-first-line-maintenance-in-patients-with-advanced-urothelial-carcinoma-and-analysis-of-subsequent-treatment.html

ASCO GU 2024: Updated Results from AVENANCE In the overall effectiveness population, the median overall survival from the start of avelumab 1st line maintenance treatment was 21.3 months. The 1- and 2- ...

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

Real-world avelumab first-line maintenance in advanced ... Long-term results from the JAVELIN Bladder 100 trial demonstrated the safety and tolerability of avelumab 1LM in patients with la/mUC, with 19. ...

7. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-bladder-cancer/158267-asco-gu-2025-real-world-effectiveness-and-safety-of-avelumab-first-line-maintenance-treatment-in-patients-with-locally-advanced-or-metastatic-urothelial-carcinoma-second-interim-analysis-of-the-avenue-study.html

Real-World Effectiveness and Safety of Avelumab First ... The median duration of avelumab maintenance treatment was 6 months. The 6-and 12-month OS rates were 80.6% (95% CI: 73.9–85.7%) and 69.1% (95% ...

8. 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 ...

9. 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 ...