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.
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.12578
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.12347
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 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.12678
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
My kidneys work well enough (creatinine clearance ≥ 30 mL/min).
My organs and bone marrow are functioning normally.
My liver function tests are within the required range.
My Merkel cell carcinoma is at stage III or IV and cannot be surgically removed.
I am 18 years old or older.
I can take care of myself but might not be able to do heavy physical work.
Exclusion Criteria
I am HIV positive.
I am currently being treated for Hepatitis B or C.
My cancer has spread to my brain.
I have received treatments other than first-line aPD1 monotherapy for my MCC.
You have an autoimmune disease that could worsen with this treatment, a history of organ transplant, an ongoing infection that needs medicine to treat it, or a serious mental health concern. You also have certain types of cancer or other health issues that could affect the study results.
I do not have serious heart problems like recent stroke, heart attack, severe heart failure, or arrhythmias needing treatment.
I take more than 10 mg of prednisone or similar medication daily.
I have severe side effects from past cancer treatment that haven't gone away.
Treatment Details
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.
1Treatment groups
Experimental Treatment
Group I: Avelumab and Radiation TherapyExperimental Treatment2 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
Find a clinic near you
Research locations nearbySelect from list below to view details:
Memorial Sloan Kettering Cancer Center (All Protocol Activities)New York, NY
Memorial Sloan Kettering Commack (All Protocol Activities)Commack, NY
Memorial Sloan Kettering Westchester (All Protocol Activities)Harrison, NY
Memorial Sloan Kettering Nassau (All Protocol Activities)Uniondale, NY
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Who is running the clinical trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
EMD SeronoIndustry Sponsor
References
Avelumab: A Review of Its Application in Metastatic Merkel Cell Carcinoma. [2020]To summarize the clinical development of avelumab and its clinical relevance in metastatic Merkel cell carcinoma (MCC).
Avelumab: A Review in Metastatic Merkel Cell Carcinoma. [2020]Avelumab (Bavencio®) is a fully human IgG1 monoclonal antibody that is directed against programmed cell death ligand 1 (PD-L1). Avelumab functions as an immune checkpoint inhibitor and has recently been approved in the USA, the EU and Japan for the treatment of metastatic Merkel cell carcinoma (MCC). It is thus the first therapeutic agent specifically approved for use in this indication, and is approved for use independent of line of treatment. Approval for avelumab in metastatic MCC was based on the two-part, single-arm, phase II trial, JAVELIN Merkel 200. In Part A of the study, confirmed objective responses were observed in approximately one-third of patients with chemotherapy-refractory metastatic MCC treated with avelumab. The responses were observed early and appeared to be durable, with an estimated 74% of responses having a duration ≥ 12 months. Furthermore, interim results from a separate cohort of patients (Part B) indicate an objective response rate for avelumab of > 60% in patients who were chemotherapy-naïve in the metastatic disease setting. Avelumab is associated with a risk of immune-related adverse events but, overall, has an acceptable and manageable safety and tolerability profile. In conclusion, currently available data suggest that avelumab presents a clinically beneficial new treatment option for metastatic MCC, a rare but aggressive cancer associated with a poor prognosis.
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]Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with a high risk of metastasis. In 2017, avelumab (anti-programmed death-ligand 1 (PD-L1)) became the first approved treatment for patients with metastatic MCC (mMCC), based on the occurrence of durable responses in a subset of patients. Here, we report long-term efficacy and safety data and exploratory biomarker analyses in patients with mMCC treated with avelumab.
Avelumab for advanced Merkel cell carcinoma in the Netherlands: a real-world cohort. [2021]Merkel cell carcinoma (MCC) is associated with high recurrence rates and poor survival when metastatic disease is present. The immune checkpoint inhibitor avelumab has shown high response rates (RRs) and durable responses in patients with advanced MCC (aMCC) in clinical trials. To date, only results from clinical trials, patients treated in an expanded access program and very small numbers of patients have been reported. In this study, detailed real-world efficacy and toxicity data of avelumab in patients with aMCC are reported.
Severe Demyelinating Polyneuropathy and Cranial Neuropathy During Avelumab Treatment of Metastatic Merkel Cell Carcinoma. [2021]Avelumab is a programmed death ligand 1-blocking monoclonal antibody used for the treatment of Merkel cell carcinoma (MCC), urothelial carcinoma, and other solid tumors. It acts as an immune checkpoint inhibitor and prolongs survival of MCC patients. Immune-mediated neurological adverse effects are rare and usually respond well to specific therapy.
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]Avelumab (anti-programmed death ligand 1 (PD-L1)) is approved in multiple countries for the treatment of metastatic Merkel cell carcinoma (mMCC), a rare and aggressive skin cancer. We report efficacy and safety data and exploratory biomarker analyses from a cohort of patients with mMCC treated with first-line avelumab in a phase II trial.
Introducing Radiotherapy in Metastatic Merkel Cell Carcinoma Patients with Limited Progression on Avelumab: An Effective Step against Primary and Secondary Immune Resistance? [2023]To investigate the ability of radiotherapy (RT) to prolong progression-free survival (PFS) and to report treatment-related toxicities among oligoprogressive metastatic Merkel cell carcinoma (mMCC) patients on avelumab.
Avelumab for Advanced Merkel Cell Carcinoma: Global Real-World Data on Patient Response and Survival. [2023]Avelumab is a programmed cell death-ligand 1 (PD-L1) inhibitor approved by the Food and Drug Administration for advanced Merkel cell carcinoma (MCC). Studies conducted in real-world settings have shed light on its effectiveness and safety in clinical settings.