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
A Randomized Phase 2 Study of ATR Inhibition in Advanced PD-(L)1-Refractory Merkel Cell Carcinoma: The MATRiX Trial
3 other identifiers
interventional
50
2 countries
51
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started May 2024
Typical duration for phase_2
51 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 13, 2023
CompletedFirst Posted
Study publicly available on registry
July 17, 2023
CompletedStudy Start
First participant enrolled
May 21, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 1, 2028
May 4, 2026
April 1, 2026
3.6 years
July 13, 2023
May 1, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Composite progression-free survival (PFS)
The stratified (on disease, acquired versus primary immune checkpoint inhibitor-refractory disease) log-rank test will be used to compare PFS between arms. The primary analysis will be done on an intent-to-treat basis. An as-treated analysis will also be done as a sensitivity analysis.
From registration to progressive disease or death whichever occurs first, assessed up to 2 years
Secondary Outcomes (4)
Overall response rate (ORR)
Up to 2 years
Duration of response
From the time measurement criteria are met for complete or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 years
Overall survival (OS)
Up to 2 years
Gene expression-based immunologic signatures predictive of response
Up to 2 years
Other Outcomes (1)
Biomarker levels
Up to 2 years
Study Arms (2)
Arm 1 (tuvusertib)
ACTIVE COMPARATORPatients 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)
Arm 2 (tuvusertib, avelumab)
EXPERIMENTALPatients 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.
Interventions
Undergo collection of blood and stool
Undergo CT or PET/CT
Given IV
Undergo biopsy
Undergo PET/CT
Undergo MRI
Given PO
Eligibility Criteria
You may qualify if:
- REGISTRATION ELIGIBILITY: Patients must have a history of pathologically confirmed locally advanced/unresectable Merkel cell carcinoma or metastatic Merkel cell carcinoma
- REGISTRATION ELIGIBILITY: Patients must have evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
- REGISTRATION ELIGIBILITY: Patients must have had prior treatment with anti-PD-1 or anti-PD-L-1 antibody (e.g., pembrolizumab, avelumab, etc.) and have experienced progressive disease during treatment or within 120 days from the last dose of anti-PD-(L)1 therapy. Anti-PD-(L)1 therapy administered in combination with other agent(s) including ipilimumab is also allowed as prior therapy, if patients experienced progressive disease during treatment or within 120 days from the last dose of anti-PD-(L)1 therapy. The last dose of anti-PD-(L)1 antibody must be ≥ 14 days prior to planned C1D1. If participants are receiving or received cytotoxic chemotherapy as most recent therapy prior to screening for this trial, there must be clinically and/or radiologically documented progressive disease on or after chemotherapy prior to being eligible for this study. If the patient is receiving bridging chemotherapy, the most recent administration must be ≥ 14 days prior to planned cycle 1 day 1 (C1D1) of the clinical trial to be eligible
- REGISTRATION ELIGIBILITY: Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of M1774/tuvusertib in combination with avelumab in patients \< 18 years of age, children are excluded from this study
- REGISTRATION ELIGIBILITY: Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- REGISTRATION ELIGIBILITY: Absolute neutrophil count \>= 1,000/mcL
- REGISTRATION ELIGIBILITY: Platelets \>= 100,000/mcL
- REGISTRATION ELIGIBILITY: Total bilirubin =\< institutional upper limit of normal (ULN) or ≤ 1.5 x ULN for subjects with Gilbert's disease
- REGISTRATION ELIGIBILITY: Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN
- REGISTRATION ELIGIBILITY: Serum creatinine =\< 1.5 x institutional ULN
- (If serum creatinine is \> 1.5 x ULN, creatinine clearance needs to be ≥ 50 mL/min by Cockcroft-Gault calculation or by a measured 24-hour urine collection for the participant to be eligible.)
- REGISTRATION ELIGIBILITY: Hemoglobin \>= 9.0 g/dL
- REGISTRATION ELIGIBILITY: Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- REGISTRATION ELIGIBILITY: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- REGISTRATION ELIGIBILITY: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- +22 more criteria
You may not qualify if:
- Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of. One example of such a reference is here (https://go.drugbank.com/categories/DBCAT003956)
- As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (51)
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
Keck Medicine of USC Koreatown
Los Angeles, California, 90020, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
USC Norris Oncology/Hematology-Newport Beach
Newport Beach, California, 92663, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California, 94304, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
Yale University
New Haven, Connecticut, 06520, United States
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016, United States
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, 33180, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, 33176, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324, United States
Moffitt Cancer Center - McKinley Campus
Tampa, Florida, 33612, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Northwestern University
Chicago, Illinois, 60611, United States
Memorial Hospital East
Shiloh, Illinois, 62269, United States
HaysMed
Hays, Kansas, 67601, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
Lawrence Memorial Hospital
Lawrence, Kansas, 66044, United States
The University of Kansas Cancer Center - Olathe
Olathe, Kansas, 66061, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211, United States
Salina Regional Health Center
Salina, Kansas, 67401, United States
University of Kansas Health System Saint Francis Campus
Topeka, Kansas, 66606, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
University Health Truman Medical Center
Kansas City, Missouri, 64108, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
Fred Hutchinson Cancer Center
Seattle, Washington, 98109, United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Paul Nghiem
Fred Hutchinson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 13, 2023
First Posted
July 17, 2023
Study Start
May 21, 2024
Primary Completion (Estimated)
January 1, 2028
Study Completion (Estimated)
January 1, 2028
Last Updated
May 4, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.