Avelumab for Merkel Cell Carcinoma

(ADAM Trial)

Recruiting at 9 trial locations

Overseen By ADAM Trial Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Washington

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Residual MCC, Distant metastasis, Prior systemic therapy, Severe autoimmune, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 24

101 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but you cannot use systemic immunosuppressive treatments like corticosteroids within 3 months before starting the trial. If you're on a low dose of corticosteroids for hormone replacement or short-term use, you might still be eligible.

What data supports the effectiveness of the drug Avelumab for treating Merkel Cell Carcinoma?

Avelumab has been shown to be effective in treating metastatic Merkel cell carcinoma, with about one-third of patients who had previously received chemotherapy experiencing significant tumor shrinkage. Additionally, more than 60% of patients who had not received prior chemotherapy also responded well to the drug, with many of these responses lasting at least a year. ^{1 2 3 4 5}

Is avelumab safe for humans?

Avelumab, also known as Bavencio, has been studied for safety in treating metastatic Merkel cell carcinoma. It is generally considered to have an acceptable safety profile, though it can cause immune-related side effects, which are manageable. ^{1 2 3 6 7}

How is the drug avelumab different from other treatments for Merkel cell carcinoma?

Avelumab is unique because it is the first drug specifically approved for treating metastatic Merkel cell carcinoma, working as an immune checkpoint inhibitor by blocking PD-L1, which helps the immune system attack cancer cells. Unlike traditional chemotherapy, avelumab can provide durable responses and is used regardless of previous treatments. ^{1 2 6 7 8}

What is the purpose of this trial?

This randomized phase III trial studies how well avelumab works in treating patients with Merkel cell cancer that has spread to the lymph nodes and have undergone surgery and/or radiation therapy. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Research Team

Shailender Bhatia, MBBS

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for adults with Merkel Cell Carcinoma (MCC) that has spread to lymph nodes, treated with surgery and/or radiation. Participants must have completed treatment within the last 120 days, be in good health with a life expectancy over 3 years, and not have any serious illnesses or immune system problems. They should agree to use effective contraception and provide consent for tissue sample collection.

Inclusion Criteria

Your hemoglobin level is at least 9 grams per deciliter.

I will begin the study treatment within 120 days after my definitive cancer therapy started.

Your platelet count is at least 100 billion per liter.

Exclusion Criteria

Pregnant or breast-feeding women

I have an autoimmune disease or had an organ transplant that needed strong immune system drugs.

Doctors suspect I still have Merkel cell carcinoma after initial checks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Phase 1

Patients receive avelumab or placebo IV over 1 hour once every 15 days

16 weeks

8 visits (in-person)

Induction Phase 2

Patients receive avelumab or placebo IV over 1 hour once every 30 days

16 weeks

4 visits (in-person)

Maintenance Phase

Patients receive avelumab or placebo IV over 1 hour once every 120 days

24 months

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 6 months for 5 years, then annually

Treatment Details

Interventions

• Avelumab

Trial Overview The study tests if Avelumab, an immunotherapy drug using monoclonal antibodies, can prevent MCC from returning after initial treatment. Patients are randomly assigned to receive either Avelumab or a placebo following their primary therapy. The trial also involves collecting blood samples for further research.

Participant Groups

Group I: Arm I (avelumab) Experimental Treatment 2 Interventions

Patients receive avelumab IV over 1 hour once every 15 days for the first 120 days (Induction Phase 1), once every 30 days for the next 120 days (Induction Phase 2), and then once every 120 days (Maintenance Phase) for a maximum of 720 days (approximately 24 months or 2 years total) in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (placebo) Placebo Group 2 Interventions

Patients receive placebo IV over 1 hour once every 15 days for the first 120 days (Induction Phase 1), once every 30 days for the next 120 days (Induction Phase 2), and then once every 120 days (Maintenance Phase) for a maximum of 720 days (approximately 24 months or 2 years total) in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

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

Findings from Research

Avelumab is a monoclonal antibody that effectively treats metastatic Merkel cell carcinoma (MCC), showing an objective response rate of 31.8% in a phase II trial with 88 previously treated patients, including 10 complete responses.

The treatment demonstrated a median overall survival of 12.9 months and a 1-year progression-free survival rate of 30%, with manageable side effects, making it a promising alternative to traditional chemotherapy for MCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab: A Review of Its Application in Metastatic Merkel Cell Carcinoma. Joseph, J., Zobniw, C., Davis, J., et al.[2020]

Avelumab is the first approved treatment specifically for metastatic Merkel cell carcinoma (MCC), showing significant efficacy with about one-third of chemotherapy-refractory patients responding positively, and 74% of these responses lasting at least 12 months.

In a separate cohort of chemotherapy-naïve patients, avelumab demonstrated an impressive objective response rate of over 60%, while maintaining a manageable safety profile despite some risk of immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab: A Review in Metastatic Merkel Cell Carcinoma. Shirley, M.[2020]

In a phase II trial involving 116 patients with metastatic Merkel cell carcinoma (mMCC), first-line treatment with avelumab resulted in a 39.7% objective response rate and a 30.2% durable response rate, indicating its efficacy in this aggressive skin cancer.

The treatment was generally well-tolerated, with 81% of patients experiencing treatment-related adverse events, but only 18.1% had severe (grade 3/4) events, and there were no treatment-related deaths, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line avelumab in a cohort of 116 patients with metastatic Merkel cell carcinoma (JAVELIN Merkel 200): primary and biomarker analyses of a phase II study. D'Angelo, SP., Lebbé, C., Mortier, L., et al.[2022]

In a study of 88 patients with metastatic Merkel cell carcinoma (mMCC) treated with avelumab, the objective response rate was 33%, with a median duration of response lasting 40.5 months, indicating significant long-term efficacy.

The long-term safety profile of avelumab was favorable, with no new adverse events reported and no treatment-related deaths, supporting its use as a standard treatment for mMCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial. D'Angelo, SP., Bhatia, S., Brohl, AS., et al.[2021]

In a real-world study of 54 patients with advanced Merkel cell carcinoma (aMCC) treated with the immune checkpoint inhibitor avelumab, the response rate was 57%, with 24% achieving a complete response, indicating significant efficacy.

The median overall survival was 25.8 months, and only 11% of patients experienced grade 3 toxicity, suggesting that avelumab is not only effective but also has a manageable safety profile in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab for advanced Merkel cell carcinoma in the Netherlands: a real-world cohort. Levy, S., Aarts, MJB., Eskens, FALM., et al.[2021]

Avelumab, a PD-L1 inhibitor, has shown overall response rates for advanced Merkel cell carcinoma (MCC) ranging from 29.1% to 72.1% in real-world studies, with median progression-free survival between 8.1 to 24.1 months, indicating its efficacy across diverse populations.

The treatment is generally safe, with common side effects including fatigue and infusion-related reactions, and it appears to be particularly effective in immunosuppressed patients, although further research is needed to evaluate long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab for Advanced Merkel Cell Carcinoma: Global Real-World Data on Patient Response and Survival. Lohray, R., Verma, KK., Wang, LL., et al.[2023]

Avelumab, an immune checkpoint inhibitor used for treating Merkel cell carcinoma, can lead to rare but severe neurological adverse effects, as demonstrated in a case of a 70-year-old man who developed diplopia and later severe demyelinating polyneuropathy after treatment.

The neurological complications observed in this patient were refractory to multiple immune suppressive treatments, highlighting the need for awareness of potential severe side effects associated with avelumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe Demyelinating Polyneuropathy and Cranial Neuropathy During Avelumab Treatment of Metastatic Merkel Cell Carcinoma. Bilić, H., Sitaš, B., Hančević, M., et al.[2021]

References

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

Avelumab: A Review of Its Application in Metastatic Merkel Cell Carcinoma. [2020]

2. France pubmed.ncbi.nlm.nih.gov

Avelumab: A Review in Metastatic Merkel Cell Carcinoma. [2020]

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

First-line avelumab in a cohort of 116 patients with metastatic Merkel cell carcinoma (JAVELIN Merkel 200): primary and biomarker analyses of a phase II study. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial. [2021]

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

Avelumab for advanced Merkel cell carcinoma in the Netherlands: a real-world cohort. [2021]

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

Avelumab for Advanced Merkel Cell Carcinoma: Global Real-World Data on Patient Response and Survival. [2023]

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

Efficacy and safety of avelumab treatment in patients with metastatic Merkel cell carcinoma: experience from a global expanded access program. [2023]

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

Severe Demyelinating Polyneuropathy and Cranial Neuropathy During Avelumab Treatment of Metastatic Merkel Cell Carcinoma. [2021]