Avelumab + Radiation Therapy for Merkel Cell Carcinoma

Recruiting at 6 trial locations

Overseen By Christoper Barker, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: aPD1 monotherapy

Must not be taking: Chemotherapy, Anti-arrhythmics, Corticosteroids

Disqualifiers: Pregnancy, CNS metastases, Cardiovascular disease, 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: Up to 2 years

18 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or treatment for Hepatitis B or C, you may need to stop or adjust those medications. Please consult with the trial team for specific guidance.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on certain medications like systemic corticosteroids or treatments for infections like Hepatitis B or C, you may need to discuss this with the trial team.

What data supports the idea that Avelumab + Radiation Therapy for Merkel Cell Carcinoma is an effective treatment?

The available research shows that Avelumab, a drug used for treating Merkel Cell Carcinoma, has shown promising results. In clinical trials, about one-third of patients who had previously not responded to chemotherapy showed positive responses to Avelumab, with many of these responses lasting for at least a year. Additionally, in patients who had not received chemotherapy before, more than 60% showed positive responses to Avelumab. This suggests that Avelumab is an effective treatment option for this aggressive cancer, offering a new hope for patients with a poor prognosis. ^{1 2 3 4 5}

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

Avelumab has shown high response rates and durable responses in patients with advanced Merkel Cell Carcinoma (MCC) in clinical trials. In the JAVELIN Merkel 200 trial, about one-third of patients with chemotherapy-resistant MCC responded to Avelumab, with many responses lasting at least 12 months. ^{1 2 3 4 5}

What safety data is available for Avelumab and radiation therapy in treating Merkel Cell Carcinoma?

Avelumab, also known as Bavencio or MSB0010718C, is a PD-L1 inhibitor approved for treating metastatic Merkel cell carcinoma (MCC). Safety data from clinical trials, such as the JAVELIN Merkel 200 study, indicate that Avelumab has an acceptable and manageable safety profile, with immune-related adverse events being a known risk. The combination of Avelumab with radiation therapy is being explored to address immune resistance, with studies reporting treatment-related toxicities. Overall, Avelumab presents a clinically beneficial treatment option for MCC, with real-world data supporting its effectiveness and safety. ^{1 2 4 6 7}

Is the combination of Avelumab and radiation therapy safe for treating Merkel Cell Carcinoma?

Avelumab, also known as Bavencio, is generally considered safe for treating metastatic Merkel cell carcinoma, with manageable side effects related to immune responses. While specific safety data for the combination with radiation therapy is limited, Avelumab alone has an acceptable safety profile based on clinical trials and real-world studies. ^{1 2 4 6 7}

Is the drug Avelumab, used with radiation therapy, a promising treatment for Merkel Cell Carcinoma?

Yes, Avelumab is a promising treatment for Merkel Cell Carcinoma. It is the first drug specifically approved for this type of cancer and has shown positive results in clinical trials, with many patients experiencing long-lasting responses. It works by helping the immune system fight the cancer more effectively. ^{1 2 4 6 8}

How is the drug Avelumab combined with radiation therapy unique for treating 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 to help the immune system attack cancer cells. When combined with radiation therapy, it may help overcome resistance to treatment and prolong the time before the cancer progresses. ^{1 2 4 6 8}

What is the purpose of this trial?

This study will test the use of comprehensive ablative radiation therapy (CART), with the immunotherapy drug avelumab, in people with Merkel cell carcinoma (MCC) that has progressed after treatment and cannot be removed with surgery. The study researchers want to find out if CART works well when combined with avelumab.

Research Team

Christoper Barker, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with advanced Merkel cell carcinoma (MCC) that has worsened after first-line treatment and can't be surgically removed. Participants must have had prior therapy with aPD1 monotherapy, adequate organ function, and all MCC sites treatable by radiation. Exclusions include other cancer treatments, brain metastases, certain infections or immunosuppression conditions, recent vaccinations, severe allergies to avelumab, or significant heart disease.

Inclusion Criteria

Your blood counts need to be within certain ranges: lymphocytes above 800/mm^3, neutrophils above 1500/mm^3, platelets above 75,000/mm^3, white blood cells above 3000/mm^3, and hemoglobin above 9 g/dL.

My kidneys work well enough (creatinine clearance ≥ 30 mL/min).

Able to provide valid written informed consent

Exclusion Criteria

I am HIV positive.

I have received treatments other than first-line aPD1 monotherapy for my MCC.

I am currently being treated for Hepatitis B or C.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive avelumab every 2 weeks and comprehensive ablative radiation therapy (CART) is initiated between the first and second dose of Avelumab

Up to 2 years

Bi-weekly visits for avelumab administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Avelumab
• Comprehensive Ablative Radiation Therapy

Trial Overview The study is examining the effectiveness of combining comprehensive ablative radiation therapy (CART) with the immunotherapy drug avelumab in treating MCC. Researchers aim to determine if CART enhances the effects of avelumab in patients whose disease progressed after initial treatment.

Participant Groups

Group I: Avelumab and Radiation Therapy Experimental Treatment 2 Interventions

Will receive avelumab at the FDA approved dose and schedule of 800 mg IV over 60 minutes (+20 minutes / -10 minutes) every 2 weeks (+/- 3 days) until treatment intolerance or disease progression occurs or 2 years of study therapy have been administered; standard of care Avelumab therapy after 2 years is permitted. Comprehensive Ablative Radiation Therapy (CART) will be initiated between the first and second dose of Avelumab. Comprehensive ablative radiation therapy will be given according to guidelines.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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

In a study of 8 patients with oligoprogressive metastatic Merkel cell carcinoma (mMCC) undergoing radiotherapy while on avelumab, the addition of radiotherapy resulted in a high objective response rate of 75% and significantly prolonged progression-free survival (PFS) after treatment, with 60% of patients remaining progression-free at 1 year.

No significant treatment-related toxicities were observed, indicating that combining radiotherapy with immunotherapy is a safe approach for managing limited progression in mMCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Introducing Radiotherapy in Metastatic Merkel Cell Carcinoma Patients with Limited Progression on Avelumab: An Effective Step against Primary and Secondary Immune Resistance? Ferini, G., Zagardo, V., Critelli, P., et al.[2023]

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 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 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]

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]

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]

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]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Introducing Radiotherapy in Metastatic Merkel Cell Carcinoma Patients with Limited Progression on Avelumab: An Effective Step against Primary and Secondary Immune Resistance? [2023]

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

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

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

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

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

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

5. 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]

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

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]

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

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