Tuvusertib + Avelumab for Merkel Cell Skin Cancer
Recruiting in Palo Alto (17 mi)
+46 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II trial compares tuvusertib in combination with avelumab to tuvusertib alone to determine whether the combination therapy will lengthen the time before the cancer starts getting worse in patients with Merkel cell cancer that has not responded to previous treatment (refractory). Tuvusertib is a drug that inhibits an enzyme called ataxia telangiectasia and Rad3 related (ATR) kinase, which is an enzyme that plays a role in repair of damaged deoxyribonucleic acid (DNA) as well as tumor cell replication and survival. It may lead to tumor cell death by inhibiting ATR kinase activity. 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. Giving tuvusertib in combination with avelumab may lengthen the time before Merkel cell cancer starts getting worse compared to giving avelumab alone.
Is the drug Avelumab a promising treatment for Merkel Cell Skin Cancer?Yes, Avelumab is a promising drug for treating Merkel Cell Skin Cancer. It is the first approved treatment specifically for this type of cancer and has shown positive results in patients, including durable responses and a good safety profile.12346
What safety data is available for the treatment of Tuvusertib + Avelumab in Merkel Cell Skin Cancer?Avelumab, a PD-L1 inhibitor, has been studied extensively in metastatic Merkel cell carcinoma (MCC). It has shown durable responses in patients, with an acceptable and manageable safety profile. The JAVELIN Merkel 200 trial reported immune-related adverse events but overall indicated that avelumab is a clinically beneficial treatment option for MCC. Long-term data from this trial supports its safety and efficacy. However, resistance to PD-L1 inhibitors like avelumab remains a challenge, and alternative treatments such as ipilimumab plus nivolumab have been explored for avelumab-refractory cases.12356
What data supports the idea that Tuvusertib + Avelumab for Merkel Cell Skin Cancer is an effective treatment?The available research shows that Avelumab, when used alone, has shown promising results in treating Merkel Cell Skin Cancer. In a study called JAVELIN Merkel 200, about one-third of patients who had not responded to previous 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. This suggests that Avelumab is an effective option for treating this type of cancer. However, there is no specific data provided on the combination of Tuvusertib and Avelumab for this condition.12345
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you must stop all current medications, but certain medications are prohibited. You cannot take proton-pump inhibitors (PPIs) or medications that strongly inhibit or induce CYP3A4 and CYP1A2 enzymes. Some drugs like metformin, acyclovir, and ciprofloxacin are also not allowed. If you are on these medications and cannot switch to alternatives, you may not be eligible. Chronic corticosteroid use over 10 mg prednisone daily is also not allowed. Please consult with your doctor for more details.
Eligibility Criteria
This trial is for adults with advanced or metastatic Merkel cell carcinoma who have previously been treated with anti-PD-1 or anti-PD-L1 therapy without success. Participants must be over 18, have a certain level of physical fitness (ECOG <=2), and meet specific blood count and organ function criteria.Inclusion Criteria
I have been diagnosed with advanced or metastatic Merkel cell carcinoma.
I can take care of myself but might not be able to do heavy physical work.
I am 18 years old or older.
Participant Groups
The MATRiX trial is testing the combination of Tuvusertib, which blocks an enzyme involved in DNA repair and tumor survival, with Avelumab, an immunotherapy drug that may help the immune system fight cancer. The goal is to see if this combo works better than just Avelumab alone for controlling disease progression.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm 2 (tuvusertib, avelumab)Experimental Treatment7 Interventions
Patients receive tuvusertib PO QD on days 1-14 of each cycle and avelumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, PET/CT, or MRI, biopsy, and collection of blood and stool at screening and on study.
Group II: Arm 1 (tuvusertib)Active Control6 Interventions
Patients receive tuvusertib PO QD on days 1-14 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, PET/CT, or MRI, biopsy, and collection of blood and stool at screening and on study. Patients with documented progression may cross over to Arm 2.
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:
Fred Hutchinson Cancer Research CenterSeattle, WA
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory CareIrvine, CA
UM Sylvester Comprehensive Cancer Center at AventuraAventura, FL
UM Sylvester Comprehensive Cancer Center at Coral GablesCoral Gables, FL
More Trial Locations
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Who is running the clinical trial?
National Cancer Institute (NCI)Lead 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.
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.
Ipilimumab plus nivolumab in avelumab-refractory Merkel cell carcinoma: a multicenter study of the prospective skin cancer registry ADOREG. [2022]Merkel cell carcinoma is a rare, highly aggressive skin cancer with neuroendocrine differentiation. Immune checkpoint inhibition has significantly improved treatment outcomes in metastatic disease with response rates to programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) inhibition of up to 62%. However, primary and secondary resistance to PD-1/PD-L1 inhibition remains a so far unsolved clinical challenge since effective and safe treatment options for these patients are lacking.Fourteen patients with advanced (non-resectable stage III or stage IV, Union international contre le cancer 2017) Merkel cell carcinoma with primary resistance to the PD-L1 inhibitor avelumab receiving subsequent therapy (second or later line) with ipilimumab plus nivolumab (IPI/NIVO) were identified in the prospective multicenter skin cancer registry ADOREG. Five of these 14 patients were reported previously and were included in this analysis with additional follow-up. Overall response rate, progression-free survival (PFS), overall survival (OS) and adverse events were analyzed.All 14 patients received avelumab as first-line treatment. Thereof, 12 patients had shown primary resistance with progressive disease in the first tumor assessment, while two patients had initially experienced a short-lived stabilization (stable disease). Six patients had at least one systemic treatment in between avelumab and IPI/NIVO. In total, 7 patients responded to IPI/NIVO (overall response rate 50%), and response was ongoing in 4 responders at last follow-up. After a median follow-up of 18.85 months, median PFS was 5.07 months (95% CI 2.43-not available (NA)), and median OS was not reached. PFS rates at 12 months and 24 months were 42.9% and 26.8 %, respectively. The OS rate at 36 months was 64.3%. Only 3 (21%) patients did not receive all 4 cycles of IPI/NIVO due to immune-related adverse events.In this multicenter evaluation, we observed high response rates, a durable benefit and promising OS rates after treatment with later-line combined IPI/NIVO. In conclusion, our patient cohort supports our prior findings with an encouraging activity of second-line or later-line IPI/NIVO in patients with anti-PD-L1-refractory Merkel cell carcinoma.
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.