Testing the Combination of two Anticancer Drugs M1774 (Tuvusertib) and Avelumab to Evaluate their Safety and Effectiveness in Treating Merkel Cell Skin Cancer, MATRiX Trial

Active:	Yes
Cancer Type:	Neuroendocrine Tumor Skin Cancer (Non-Melanoma) Unknown Primary	NCT ID:	NCT05947500
Trial Phases:	Phase II	Protocol IDs:	10592 (primary) 10592 NCI-2023-05259
Eligibility:	18 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	WA008 Fred Hutchinson Cancer Center
NCI Full Details:	http://clinicaltrials.gov/show/NCT05947500

Summary

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.

Objectives

PRIMARY OBJECTIVE:
I. To compare the potential efficacy, using progression free survival (PFS), of ATR inhibition alone to ATR inhibition plus anti-PD-(L)1 therapy through a randomized clinical trial for patients with advanced Merkel cell carcinoma (MCC) who have progressed on anti-PD(L)1 therapy.

SECONDARY OBJECTIVES:
I. To compare the clinical activity of ATR inhibition alone to that in combination with avelumab through a randomized clinical trial for patients with advanced MCC that has progressed after PD-1 pathway blockade.
II. To identify gene expression-based immunologic (replication stress / neuroendocrine [NE] differentiation) signatures predictive of response to ATR inhibition in advanced immunotherapy-refractory MCC tumors through ribonucleic acid sequencing (RNAseq).

EXPLORATORY OBJECTIVES:
I. To examine the association of various biomarkers with the clinical activity of ATR inhibition alone or in combination with PD-(L)1 pathway blockade.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: Patients receive tuvusertib orally (PO) once daily (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 computed tomography (CT), positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI), biopsy, and collection of blood and stool/rectal swabs at screening and on study. Patients with documented progression may cross over to Arm 2.

ARM 2: Patients receive tuvusertib PO QD on days 1-14 of each cycle and avelumab intravenously (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.

After completion of study treatment, patients are followed up at 30 days and then every 6 months for 2 years.

Treatment Sites in Georgia

Winship Cancer Institute of Emory University
1365 Clifton Road NE
Building C
Atlanta, GA 30322
winshipcancer.emory.edu

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