Avelumab + Radiation for Bladder Cancer

Recruiting at1 trial location

Overseen by Kent Mouw, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Dana-Farber Cancer Institute

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This research study is studying the effects of adding a certain type of immunotherapy to standard bladder-directed radiation as a treatment for muscle-invasive urothelial carcinoma of the bladder. The drug in this study is: Avelumab (also known as BAVENCIO®)

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.

What data supports the idea that Avelumab + Radiation for Bladder Cancer is an effective treatment?

The available research shows that Avelumab, when used as a maintenance treatment after initial chemotherapy for advanced bladder cancer, can help prolong the life of patients. Although the specific combination of Avelumab and radiation for bladder cancer isn't directly discussed, Avelumab alone has shown promising results in improving survival rates for patients with advanced bladder cancer. This suggests that Avelumab could be an effective part of a treatment plan for bladder cancer. ^{1 2 3 4 5}

What safety data exists for Avelumab and Radiation in bladder cancer treatment?

Avelumab, also known as Bavencio, has been evaluated for safety in several studies involving patients with advanced urothelial carcinoma. In a phase Ib study, common treatment-related adverse events included fatigue, infusion-related reactions, and nausea, with serious adverse events occurring in a small percentage of patients. Avelumab was generally well tolerated, with durable responses and prolonged survival observed. In a broader analysis of 21 trials, Avelumab monotherapy showed a 73.78% incidence of all-grade treatment-related adverse events, with 14.44% being high-grade. The data suggests Avelumab has a manageable safety profile, but specific safety data for the combination with radiation therapy in bladder cancer is not detailed in the provided research. ^{1 3 5 6 7}

Is Avelumab, a drug used with radiation, a promising treatment for bladder cancer?

Yes, Avelumab combined with radiation is promising for bladder cancer. It helps the immune system fight cancer cells and has been shown to improve survival in patients with advanced bladder cancer. ^{1 3 5 8 9}

Research Team

Kent Mouw, MD, PhD

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

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.

Treatment Details

Interventions

• Avelumab (Monoclonal Antibodies)
• Radiation (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.

Participant Groups

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 Japan for the following indications:

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+

Dr. Benjamin L. Ebert

Dana-Farber Cancer Institute

Chief Executive Officer

MD from Harvard Medical School, PhD from Oxford University

Dr. Craig A. Bunnell

Dana-Farber Cancer Institute

Chief Medical Officer since 2012

MD from Harvard Medical School, MPH from Harvard School of Public Health, MBA from MIT Sloan School of Management

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

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]

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 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]

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, 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, 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]

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, 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]

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. United States 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. [2023]

3. 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]

4. England 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. [2021]

5. 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]

6. United States 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. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety profile of avelumab monotherapy. [2021]

8. 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]

9. England pubmed.ncbi.nlm.nih.gov

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