Tuvusertib + Avelumab for Merkel Cell Skin Cancer

Not currently recruiting at 58 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Proton-pump inhibitors, CYP3A4 inhibitors

Disqualifiers: Ataxia telangiectasia, Uncontrolled illness, 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: 23

Duration: 21-day cycles, repeated until disease progression or unacceptable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining two treatments, tuvusertib and avelumab, can delay the progression of Merkel cell skin cancer compared to tuvusertib alone. Tuvusertib blocks an enzyme that aids cancer cell survival, while avelumab is an immunotherapy that enhances the body's ability to fight cancer. The researchers aim to determine if the combination can better control cancer that hasn't responded to previous treatments. Individuals with Merkel cell cancer that has not improved after other treatments might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

You may need to stop taking certain medications if they interact with the trial drugs. Specifically, you cannot take strong inhibitors or inducers of certain enzymes (like CYP3A4 and CYP1A2) or certain other drugs like metformin and ciprofloxacin. It's important to discuss your current medications with the trial team to see if any changes are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that avelumab is generally safe and well-tolerated by patients. Some individuals might experience immune-related side effects, but these can usually be managed. Tuvusertib has not been as extensively studied yet, but it is currently being tested with avelumab to assess its safety. This trial is in an early stage and is still exploring how well patients can tolerate tuvusertib. Since the FDA has already approved avelumab for treating Merkel cell carcinoma, there is some confidence in its safety when used alone. The trial aims to determine if combining it with tuvusertib is also safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Tuvusertib and Avelumab offer a novel approach to tackling Merkel cell skin cancer. Unlike traditional treatments that may rely solely on chemotherapy or radiation, Tuvusertib targets specific cellular pathways involved in cancer growth, potentially leading to more precise and effective intervention. Avelumab, on the other hand, is an immunotherapy that helps the body's immune system recognize and attack cancer cells. This combination aims to enhance the body's natural defenses while directly interfering with cancer cell proliferation, offering hope for improved outcomes over current standard therapies.

What evidence suggests that this trial's treatments could be effective for Merkel cell cancer?

In this trial, participants will receive either tuvusertib alone or a combination of tuvusertib and avelumab. Research has shown that using tuvusertib and avelumab together might slow the progression of Merkel cell cancer. Tuvusertib blocks a protein that aids cancer cells in repairing their DNA, potentially leading to cell death. Avelumab boosts the immune system to help it attack cancer cells. Studies have found that avelumab alone is very effective, with high response rates and long-lasting effects in treating Merkel cell cancer. These findings suggest that combining both drugs could be more effective than using avelumab alone. ^{6 7 8 9 10}

Who Is on the Research Team?

Paul Nghiem

Principal Investigator

Fred Hutchinson Cancer Center

Are You a Good Fit for This Trial?

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.

Your liver enzyme levels are not more than three times the normal limit.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive tuvusertib orally once daily on days 1-14 of each 21-day cycle. In Arm 2, participants also receive avelumab intravenously on day 1 of each cycle.

21-day cycles, repeated until disease progression or unacceptable toxicity

Every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then every 6 months for 2 years.

2 years

1 visit at 30 days, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Avelumab
• Biopsy
• Biospecimen Collection
• Computed Tomography
• Magnetic Resonance Imaging
• Positron Emission Tomography
• Tuvusertib

Trial Overview 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.

How Is the Trial Designed?

Group I: Arm 2 (tuvusertib, avelumab) Experimental Treatment 7 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 Control 6 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. (CLOSED TO ACCRUAL 5/12/2025)

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 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 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 14 patients with advanced Merkel cell carcinoma who were resistant to the PD-L1 inhibitor avelumab, treatment with ipilimumab plus nivolumab (IPI/NIVO) resulted in a 50% overall response rate, indicating significant efficacy in this challenging patient population.

After a median follow-up of nearly 19 months, the treatment showed promising progression-free survival (PFS) and overall survival (OS) rates, with 12-month PFS at 42.9% and a 36-month OS rate of 64.3%, suggesting durable benefits from IPI/NIVO even in patients previously resistant to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab plus nivolumab in avelumab-refractory Merkel cell carcinoma: a multicenter study of the prospective skin cancer registry ADOREG. Glutsch, V., Schummer, P., Kneitz, H., et al.[2022]

Citations

1. merkelcell.org merkelcell.org/news-and-publications/2025/real-world-safety-and-effectiveness-of-avelumab-in-immune-compromised-ic-and-non-ic-patients-with-merkel-cell-carcinoma-mcc-results-from-a-prospective-german-registry-mcc-trim/

Real-world safety and effectiveness of avelumab in immune ... Real-world safety and effectiveness of avelumab in immune-compromised (IC) and non-IC patients with Merkel cell carcinoma (MCC): Results from a ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9394192/

Real-world clinical outcomes with avelumab in patients with ... This real-world study of patients with advanced MCC demonstrated that avelumab treatment resulted in a high response rate with durable responses and prolonged ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.9543

Results from a prospective German registry (MCC-TRIM). Survival outcomes with first-line avelumab treatment were assessed using the Kaplan-Meier method. Results: Among 875 patients with MCC (various ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9536833/

Avelumab for the treatment of metastatic Merkel cell carcinoma Avelumab, a PD-L1 inhibitor, has demonstrated an acceptable toxicity profile and a significant response rate in patients with MCC. Avelumab is thus a promising ...

5. esmoopen.com esmoopen.com/article/S2059-7029(24)01229-8/fulltext

4-year follow-up from part B of the JAVELIN Merkel 200 study First-line avelumab monotherapy led to long-term OS in patients with mMCC. After 4 years of follow-up, the median OS was 20.3 months and the 4-year OS rate was ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS9598

The MATRiX trial: A multicenter, randomized, phase II study ... Background: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer driven by UV mutations or the Merkel cell polyomavirus (MCPyV).

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-05259

Testing the Combination of two Anticancer Drugs M1774 ... Giving tuvusertib in combination with avelumab may lengthen the time before Merkel cell cancer starts getting worse compared to giving avelumab alone.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05947500

Study Details | NCT05947500 | Testing the Combination of ... Giving tuvusertib in combination with avelumab may lengthen the time before Merkel cell cancer starts getting worse compared to giving avelumab alone. Detailed ...

9. withpower.com withpower.com/trial/phase-2-carcinoma-merkel-cell-9-2023-05a5f

Tuvusertib + Avelumab for Merkel Cell Skin Cancer Avelumab, used for treating Merkel Cell Carcinoma, has been shown to have an acceptable and manageable safety profile, with some risk of immune-related side ...

10. asco.org asco.org/abstracts-presentations/ABSTRACT496168

The MATRiX trial: A multicenter, randomized, phase II study ... Background: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer driven by UV mutations or the Merkel cell polyomavirus (MCPyV).