Avelumab + Radiation Therapy for Merkel Cell Carcinoma

Recruiting in Palo Alto (17 mi)

+6 other locations

Overseen by Christoper Barker, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Memorial Sloan Kettering Cancer Center

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

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.

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.

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 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 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}

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.

Treatment Details

Interventions

• Avelumab (Monoclonal Antibodies)
• Comprehensive Ablative Radiation Therapy (Radiation)

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 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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Lisa M. DeAngelis

Memorial Sloan Kettering Cancer Center

Chief Medical Officer since 2021

MD from Columbia University

Selwyn M. Vickers

Memorial Sloan Kettering Cancer Center

Chief Executive Officer since 2022

MD from Johns Hopkins University

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, 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]