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AzTrials

Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8Phase 2NCT05947500

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 Phase 2 study testing Avelumab, Biopsy Procedure and Biospecimen Collection in people with Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8 and Clinical Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8, run by National Cancer Institute (NCI) at 51 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Avelumab, Biopsy Procedure and Biospecimen Collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
51 sitesin 2 countries
Study dates
21 May 2024to 1 Jan 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • REGISTRATION ELIGIBILITY: Patients with treated brain metastases are eligible if follow-up brain imaging during screening shows no evidence of progressive brain metastases and it has been at least 4 weeks since central nervous system (CNS) directed therapy
  • REGISTRATION ELIGIBILITY: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • REGISTRATION ELIGIBILITY: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • REGISTRATION ELIGIBILITY: The effects of M1774(tuvusertib) on the developing human fetus are unknown. For this reason and because ATR inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and, for the duration of study participation, and 6 months after completion of M1774 (tuvusertib) and avelumab administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of M1774 (tuvusertib) and avelumab administration
  • REGISTRATION ELIGIBILITY: Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
  • CROSSOVER ELIGIBILITY: Patient was initially assigned to arm 1 (M1774/tuvusertib monotherapy) and completed at least 21 of 28 possible doses of M1774/ tuvusertib
  • CROSSOVER ELIGIBILITY: Patients must have documented progressive disease per RECIST v 1.1
  • CROSSOVER ELIGIBILITY: ECOG performance status ≤ 2 (Karnofsky ≥ 60%)
  • CROSSOVER ELIGIBILITY: Absolute neutrophil count ≥ 1,000/mcL (within 14 days of crossover registration)
  • CROSSOVER ELIGIBILITY: Platelets ≥ 100,000/mcL (within 14 days of crossover registration)
  • CROSSOVER ELIGIBILITY: Total bilirubin ≤ institutional upper limit of normal (ULN) or ≤ 1.5 x ULN for subjects with Gilbert's disease (within 14 days of crossover registration)
  • CROSSOVER ELIGIBILITY: AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN (within 14 days of crossover registration)
  • CROSSOVER ELIGIBILITY: Serum creatinine ≤ 1.5 x institutional ULN (within 14 days of crossover registration)
  • (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.)
  • CROSSOVER ELIGIBILITY: Hemoglobin ≥ 9.0 g/dL (within 14 days of crossover registration)
  • CROSSOVER ELIGIBILITY: Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • CROSSOVER ELIGIBILITY: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • CROSSOVER 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
  • CROSSOVER ELIGIBILITY: Patients with treated brain metastases are eligible if follow-up brain imaging during screening shows no evidence of progressive brain metastases and it has been at least 4 weeks since central nervous system (CNS) directed therapy
  • CROSSOVER ELIGIBILITY: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • CROSSOVER ELIGIBILITY: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • CROSSOVER ELIGIBILITY: The effects of M1774 (tuvusertib) on the developing human fetus are unknown. For this reason and because ATR inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and, for the duration of study participation, and 6 months after completion of M1774 (tuvusertib) and avelumab administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of M1774 (tuvusertib) and avelumab administration

Who cannot join

  • REGISTRATION EXCLUSION: Patients with life-threatening immune-related adverse events (IRAEs) related to prior anti-PD-(L)1 antibody. Patients with a history of IRAE of grade 4 (G4) severity (excluding thyroid or endocrine disorders now controlled) or IRAE of any severity that required permanent treatment discontinuation with prior immune checkpoint inhibitor (ICI) therapy due to toxicity
  • REGISTRATION EXCLUSION: Patients with a prior history of ataxia telangiectasia
  • REGISTRATION EXCLUSION: Patients who are receiving any other investigational agents
  • REGISTRATION EXCLUSION: History of allergic reactions attributed to compounds of similar chemical or biologic composition to M1774/tuvusertib or avelumab
  • REGISTRATION EXCLUSION: Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
  • REGISTRATION EXCLUSION: Pregnant women are excluded from this study because M1774 (tuvusertib) and avelumab have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M1774 (tuvusertib) and avelumab breastfeeding should be discontinued if the mother is treated with M1774 (tuvusertib) or avelumab and for at least 1 month after the last dose of study medications. These potential risks may also apply to other agents used in this study
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  • REGISTRATION EXCLUSION: Patients who are not able to swallow orally administered medication or have gastrointestinal disorders likely to interfere with absorption of the study medication
  • REGISTRATION EXCLUSION: Patients who cannot discontinue proton-pump inhibitors (PPIs)
  • REGISTRATION EXCLUSION: Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia and neuropathy, which may be =< grade 2. Patients with endocrinopathies requiring hormone replacement (such as hypothyroidism, autoimmune diabetes mellitus, adrenal insufficiency) will be allowed
  • REGISTRATION EXCLUSION: M1774/ tuvusertib is primarily metabolized by aldehyde oxidase and to a lesser extent CYP3A4 and CYP1A2; therefore, concomitant administration with strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir) and CYP1A2 or inducers of CYP3A4 (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) and CYP1A2 are prohibited. M1774/ tuvusertib is an inhibitor of MATE1 and MATE2K and substrates of these transporters are also prohibited. These include metformin, acyclovir, estrone sulfate, ciprofloxacin and cephalexin. Patients who are taking such medications who cannot discontinue or switch them to an acceptable alternative are not eligible
  • 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
  • REGISTRATION EXCLUSION: Patients who are on chronic corticosteroid treatment exceeding 10 mg prednisone daily (or equivalent) are excluded. Chronic corticosteroid use lower than this range is permitted
  • REGISTRATION EXCLUSION: Patients with a QTcF (using the Fridericia correction calculation) of > 470 msec
  • CROSSOVER EXCLUSION: Patients with life-threatening immune-related adverse events (IRAEs) related to prior anti-PD-(L)1 antibody. Patients with a history of IRAE of G4 severity (excluding thyroid or endocrine disorders now controlled) or IRAE of any severity that required permanent treatment discontinuation with prior ICI therapy due to toxicity
  • CROSSOVER EXCLUSION: Patients with a prior history of ataxia telangiectasia.
  • CROSSOVER EXCLUSION: Patients who are receiving any other investigational agents
  • CROSSOVER EXCLUSION: History of allergic reactions attributed to compounds of similar chemical or biologic composition to M1774/tuvusertib or avelumab
  • CROSSOVER EXCLUSION: Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
  • CROSSOVER EXCLUSION: Pregnant women are excluded from this study because M1774 (tuvusertib) and avelumab have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M1774 (tuvusertib) and avelumab breastfeeding should be discontinued if the mother is treated with M1774 (tuvusertib) or avelumab and for at least 1 month after the last dose of study medications. These potential risks may also apply to other agents used in this study
  • CROSSOVER EXCLUSION: Patients who are not able to swallow orally administered medication or have gastrointestinal disorders likely to interfere with absorption of the study medication
  • CROSSOVER EXCLUSION: Patients who cannot discontinue proton-pump inhibitors (PPIs)
  • CROSSOVER EXCLUSION: Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia and neuropathy which may be ≤ grade 2. Additionally, anemia felt related to M1774/tuvusertib may be grade 2 as long as it exceeds requirement of hemoglobin > 9 g/dL. Patients with endocrinopathies requiring hormone replacement (such as hypothyroidism, autoimmune diabetes mellitus, adrenal insufficiency) will be allowed
  • CROSSOVER EXCLUSION: M1774/ tuvusertib is primarily metabolized by aldehyde oxidase and to a lesser extent CYP3A4 and CYP1A2; therefore, concomitant administration with strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir) and CYP1A2 or inducers of CYP3A4 (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) and CYP1A2 are prohibited. M1774/ tuvusertib is an inhibitor of MATE1 and MATE2K and substrates of these transporters are also prohibited. These include metformin, acyclovir, estrone sulfate, ciprofloxacin and cephalexin. Patients who are taking such medications who cannot discontinue or switch them to an acceptable alternative are not eligible. 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). Patient Drug Information Handout and Wallet Card) should be provided to patients. 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
  • CROSSOVER EXCLUSION: Patients who are on chronic corticosteroid treatment exceeding 10 mg prednisone daily (or equivalent) are excluded. Chronic corticosteroid use lower than this range is permitted
  • CROSSOVER EXCLUSION: Patients with a QTcF (using the Fridericia correction calculation) of > 470 msec

Trial locations and contacts

51 sites in 2 countries.

51 sites in 2 countries

United States50 sites

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • UM Sylvester Comprehensive Cancer Center at Aventura

    Aventura, Florida, 33180

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Northwestern University

    Chicago, Illinois, 60611

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • HaysMed

    Hays, Kansas, 67601

  • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

    Irvine, California, 92612

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • University Health Truman Medical Center

    Kansas City, Missouri, 64108

  • University of Kansas Cancer Center - North

    Kansas City, Missouri, 64154

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • Lawrence Memorial Hospital

    Lawrence, Kansas, 66044

  • University of Kansas Cancer Center - Lee's Summit

    Lee's Summit, Missouri, 64064

  • Keck Medicine of USC Koreatown

    Los Angeles, California, 90020

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • UM Sylvester Comprehensive Cancer Center at Kendall

    Miami, Florida, 33176

  • Yale University

    New Haven, Connecticut, 06520

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • USC Norris Oncology/Hematology-Newport Beach

    Newport Beach, California, 92663

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • The University of Kansas Cancer Center - Olathe

    Olathe, Kansas, 66061

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • University of Kansas Cancer Center-Overland Park

    Overland Park, Kansas, 66210

  • University of Kansas Hospital-Indian Creek Campus

    Overland Park, Kansas, 66211

  • Stanford Cancer Institute Palo Alto

    Palo Alto, California, 94304

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • UM Sylvester Comprehensive Cancer Center at Plantation

    Plantation, Florida, 33324

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Salina Regional Health Center

    Salina, Kansas, 67401

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Fred Hutchinson Cancer Center

    Seattle, Washington, 98109

  • Memorial Hospital East

    Shiloh, Illinois, 62269

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

  • Moffitt Cancer Center - McKinley Campus

    Tampa, Florida, 33612

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • University of Kansas Health System Saint Francis Campus

    Topeka, Kansas, 66606

  • Sibley Memorial Hospital

    Washington D.C., District of Columbia, 20016

  • University of Kansas Hospital-Westwood Cancer Center

    Westwood, Kansas, 66205

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

Canada1 site

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Randomized Phase 2 Study of ATR Inhibition in Advanced PD-(L)1-Refractory Merkel Cell Carcinoma: The MATRiX 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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

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

II. To explore the safety and efficacy (PFS, overall response rate [ORR], and overall survival [OS]) of the addition of avelumab to M1774 (tuvusertib) after documented progressive disease of M1774 (tuvusertib) monotherapy.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1 (CLOSED TO ACCRUAL 5/12/2025): 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 who are deriving clinical benefit despite progression may be allowed to continue treatment beyond progression, following consultation. 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 who are deriving clinical benefit despite progression may be allowed to continue treatment beyond progression, following consultation. 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 from the last dose of treatment.

Being tested
Avelumab, Biopsy Procedure, Biospecimen Collection, Computed Tomography, Magnetic Resonance Imaging
Medical subject headings
Carcinoma, Merkel Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AvelumabDrug

    Also called Bavencio, MSB 0010718C, MSB-0010718C, MSB0010718C

    Given IV

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood and stool

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT or PET/CT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/CT

  • TuvusertibDrug

    Also called ATR Kinase Inhibitor M1774, M 1774, M-1774, M1774

    Given PO

Study groups in NCT05947500
Study groupRoleWhat they receive
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 who are deriving clinical benefit despite progression may be allowed to continue treatment beyond progression, following consultation. 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)
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Drug: Tuvusertib
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 who are deriving clinical benefit despite progression may be allowed to continue treatment beyond progression, following consultation. Patients also undergo CT, PET/CT, or MRI, biopsy, and collection of blood and stool at screening and on study.
Receives: Drug: Avelumab; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Drug: Tuvusertib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: From registration to progressive disease or death whichever occurs first, assessed up to 2 years

Secondary outcomes (4)

  1. Overall response rate (ORR)

    The sum of complete and partial responses per Response Evaluation Criteria in Solid Tumors 1.1 criteria. Evaluated using the Mantel-Haenszel test.

    Measured: Up to 2 years

  2. Duration of response

    Will be evaluated by estimating the probability of response using a cumulative incidence estimate, and then among those who responded, creating a time-to-recurrence curve using a cumulative-incidence estimate. Will be compared between arms using the stratified log-rank test and the Mantel-Haenszel test will be used to compare binary outcomes.

    Measured: 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

  3. Overall survival (OS)

    Will be evaluated using a stratified log-rank test. Will be compared between arms using the stratified log-rank test and the Mantel-Haenszel test will be used to compare binary outcomes.

    Measured: Up to 2 years

  4. Gene expression-based immunologic signatures predictive of response

    Annotated transcriptome sequences at baseline and on-therapy will be correlated with response in both virus-positive and -negative tumors. Descriptive statistical analyses will be performed. Volcano plots will be evaluated. Gene set enrichment analysis will be used to compare pre-treatment samples from patients with response to treatment to samples from patients experiencing disease progression. The Kolmogorov-Smirnov test will be used to test for statistical differences followed by the Bonferroni correction to adjust for multiple comparisons.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jul 2023
  2. Study start21 May 2024
  3. Primary completion1 Jan 2028 (estimated)
  4. Study completion1 Jan 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05947500
Sponsor's protocol ID
NCI-2023-05259
Other IDs
NCI-2023-05259, 10592, 10592, P30CA015704
Status last verified
Jul 2026
First submitted
13 Jul 2023
Last updated
31 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Avelumab, Biopsy Procedure and Biospecimen Collection in people with Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8 and Clinical Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8, run by National Cancer Institute (NCI) at 51 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 37 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 51 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite progression-free survival (PFS) (time frame: From registration to progressive disease or death whichever occurs first, assessed up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05947500.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.

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