Ignite Creation Date:
2025-12-26 @ 12:15 PM
Ignite Modification Date:
2026-01-01 @ 1:10 AM
Study NCT ID:
NCT05947500
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-11-19
First Post:
2023-07-13
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
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
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015266', 'term': 'Carcinoma, Merkel Cell'}], 'ancestors': [{'id': 'D027601', 'term': 'Polyomavirus Infections'}, {'id': 'D004266', 'term': 'DNA Virus Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D014412', 'term': 'Tumor Virus Infections'}, {'id': 'D018278', 'term': 'Carcinoma, Neuroendocrine'}, {'id': 'D018358', 'term': 'Neuroendocrine Tumors'}, {'id': 'D017599', 'term': 'Neuroectodermal Tumors'}, {'id': 'D009373', 'term': 'Neoplasms, Germ Cell and Embryonal'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D000230', 'term': 'Adenocarcinoma'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000609138', 'term': 'avelumab'}, {'id': 'D001706', 'term': 'Biopsy'}, {'id': 'D013048', 'term': 'Specimen Handling'}, {'id': 'D009682', 'term': 'Magnetic Resonance Spectroscopy'}], 'ancestors': [{'id': 'D003581', 'term': 'Cytodiagnosis'}, {'id': 'D003584', 'term': 'Cytological Techniques'}, {'id': 'D019411', 'term': 'Clinical Laboratory Techniques'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D003949', 'term': 'Diagnostic Techniques, Surgical'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}, {'id': 'D008919', 'term': 'Investigative Techniques'}, {'id': 'D013057', 'term': 'Spectrum Analysis'}, {'id': 'D002623', 'term': 'Chemistry Techniques, Analytical'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2025-08-04', 'size': 584175, 'label': 'Informed Consent Form', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_000.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2025-11-17T08:17', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 50}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2024-05-21', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-10', 'completionDateStruct': {'date': '2028-01-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-11-18', 'studyFirstSubmitDate': '2023-07-13', 'studyFirstSubmitQcDate': '2023-07-13', 'lastUpdatePostDateStruct': {'date': '2025-11-19', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2023-07-17', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-01-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Biomarker levels', 'timeFrame': 'Up to 2 years', 'description': 'Will examine the association of various biomarkers with the primary and secondary endpoints. All patients will be combined for these purposes, and separate examination of biomarkers will be conducted by treatment group to allow for the possibility that certain correlates will have differing associations with outcome according to treatment group. This will be done using logistic regression for ORR and Cox regression for OS and PFS. In addition, descriptive statistics for biomarkers will be presented (mean, standard deviation, median, and interquartile range) by treatment group and based on presence or absence of response. Biomarker levels will also be compared between the two treatment groups using the two-sample t-test (or the non-parametric Wilcoxon rank-sum test as needed).'}], 'primaryOutcomes': [{'measure': 'Composite progression-free survival (PFS)', 'timeFrame': 'From registration to progressive disease or death whichever occurs first, assessed up to 2 years', 'description': '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.'}], 'secondaryOutcomes': [{'measure': 'Overall response rate (ORR)', 'timeFrame': 'Up to 2 years', 'description': 'The sum of complete and partial responses per Response Evaluation Criteria in Solid Tumors 1.1 criteria. Evaluated using the Mantel-Haenszel test.'}, {'measure': 'Duration of response', 'timeFrame': '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', 'description': '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.'}, {'measure': 'Overall survival (OS)', 'timeFrame': 'Up to 2 years', 'description': '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.'}, {'measure': 'Gene expression-based immunologic signatures predictive of response', 'timeFrame': 'Up to 2 years', 'description': '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.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8', 'Clinical Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8', 'Locally Advanced Merkel Cell Carcinoma', 'Metastatic Merkel Cell Carcinoma', 'Refractory Merkel Cell Carcinoma', 'Unresectable Merkel Cell Carcinoma']}, 'descriptionModule': {'briefSummary': "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.", 'detailedDescription': 'PRIMARY OBJECTIVE:\n\nI. 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.\n\nSECONDARY OBJECTIVES:\n\nI. 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.\n\nII. 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).\n\nEXPLORATORY OBJECTIVES:\n\nI. To examine the association of various biomarkers with the clinical activity of ATR inhibition alone or in combination with PD-(L)1 pathway blockade.\n\nII. 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.\n\nOUTLINE: Patients are randomized to 1 of 2 arms.\n\nARM 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 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.\n\nARM 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.\n\nAfter 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* REGISTRATION ELIGIBILITY: Patients must have a history of pathologically confirmed locally advanced/unresectable Merkel cell carcinoma or metastatic Merkel cell carcinoma\n* REGISTRATION ELIGIBILITY: Patients must have evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1\n* 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\n* 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\n* REGISTRATION ELIGIBILITY: Eastern Cooperative Oncology Group (ECOG) performance status =\\< 2 (Karnofsky \\>= 60%)\n* REGISTRATION ELIGIBILITY: Absolute neutrophil count \\>= 1,000/mcL\n* REGISTRATION ELIGIBILITY: Platelets \\>= 100,000/mcL\n* REGISTRATION ELIGIBILITY: Total bilirubin =\\< institutional upper limit of normal (ULN) or ≤ 1.5 x ULN for subjects with Gilbert's disease\n* REGISTRATION ELIGIBILITY: Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \\[SGOT\\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]) =\\< 3 x institutional ULN\n* REGISTRATION ELIGIBILITY: Serum creatinine =\\< 1.5 x institutional ULN\n\n * (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.)\n* REGISTRATION ELIGIBILITY: Hemoglobin \\>= 9.0 g/dL\n* 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\n* 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\n* 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\n* 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\n* 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\n* 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\n* 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\n* 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\n* CROSSOVER ELIGIBILITY: Patient was initially assigned to arm 1 (M1774/tuvusertib monotherapy) and completed at least 21 of 28 possible doses of M1774/ tuvusertib\n* CROSSOVER ELIGIBILITY: Patients must have documented progressive disease per RECIST v 1.1\n* CROSSOVER ELIGIBILITY: ECOG performance status ≤ 2 (Karnofsky ≥ 60%)\n* CROSSOVER ELIGIBILITY: Absolute neutrophil count ≥ 1,000/mcL (within 14 days of crossover registration)\n* CROSSOVER ELIGIBILITY: Platelets ≥ 100,000/mcL (within 14 days of crossover registration)\n* 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)\n* CROSSOVER ELIGIBILITY: AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN (within 14 days of crossover registration)\n* CROSSOVER ELIGIBILITY: Serum creatinine ≤ 1.5 x institutional ULN (within 14 days of crossover registration)\n\n * (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.)\n* CROSSOVER ELIGIBILITY: Hemoglobin ≥ 9.0 g/dL (within 14 days of crossover registration)\n* 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\n* 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\n* 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\n* 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\n* 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\n* 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\n* 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\n\nExclusion Criteria:\n\n* 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\n* REGISTRATION EXCLUSION: Patients with a prior history of ataxia telangiectasia\n* REGISTRATION EXCLUSION: Patients who are receiving any other investigational agents\n* REGISTRATION EXCLUSION: History of allergic reactions attributed to compounds of similar chemical or biologic composition to M1774/tuvusertib or avelumab\n* REGISTRATION EXCLUSION: Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous\n* 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\n* 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\n* REGISTRATION EXCLUSION: Patients who cannot discontinue proton-pump inhibitors (PPIs)\n* 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\n* 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\n\n * 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)\n * 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\n* 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\n* REGISTRATION EXCLUSION: Patients with a QTcF (using the Fridericia correction calculation) of \\> 470 msec\n* 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\n* CROSSOVER EXCLUSION: Patients with a prior history of ataxia telangiectasia.\n* CROSSOVER EXCLUSION: Patients who are receiving any other investigational agents\n* CROSSOVER EXCLUSION: History of allergic reactions attributed to compounds of similar chemical or biologic composition to M1774/tuvusertib or avelumab\n* CROSSOVER EXCLUSION: Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous\n* 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\n* 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\n* CROSSOVER EXCLUSION: Patients who cannot discontinue proton-pump inhibitors (PPIs)\n* 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\n* 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\n* 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\n* CROSSOVER EXCLUSION: Patients with a QTcF (using the Fridericia correction calculation) of \\> 470 msec"}, 'identificationModule': {'nctId': 'NCT05947500', 'briefTitle': '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', 'organization': {'class': 'NIH', 'fullName': 'National Cancer Institute (NCI)'}, 'officialTitle': 'A Randomized Phase 2 Study of ATR Inhibition in Advanced PD-(L)1-Refractory Merkel Cell Carcinoma: The MATRiX Trial', 'orgStudyIdInfo': {'id': 'NCI-2023-05259'}, 'secondaryIdInfos': [{'id': 'NCI-2023-05259', 'type': 'REGISTRY', 'domain': 'CTRP (Clinical Trial Reporting Program)'}, {'id': '10592', 'type': 'OTHER', 'domain': 'Dana-Farber - Harvard Cancer Center LAO'}, {'id': '10592', 'type': 'OTHER', 'domain': 'CTEP'}, {'id': 'P30CA015704', 'link': 'https://reporter.nih.gov/quickSearch/P30CA015704', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Arm 1 (tuvusertib)', 'description': '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)', 'interventionNames': ['Procedure: Biopsy Procedure', 'Procedure: Biospecimen Collection', 'Procedure: Computed Tomography', 'Procedure: Magnetic Resonance Imaging', 'Procedure: Positron Emission Tomography', 'Drug: Tuvusertib']}, {'type': 'EXPERIMENTAL', 'label': 'Arm 2 (tuvusertib, avelumab)', 'description': '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.', 'interventionNames': ['Drug: Avelumab', 'Procedure: Biopsy Procedure', 'Procedure: Biospecimen Collection', 'Procedure: Computed Tomography', 'Procedure: Magnetic Resonance Imaging', 'Procedure: Positron Emission Tomography', 'Drug: Tuvusertib']}], 'interventions': [{'name': 'Avelumab', 'type': 'DRUG', 'otherNames': ['Bavencio', 'MSB 0010718C', 'MSB-0010718C', 'MSB0010718C'], 'description': 'Given IV', 'armGroupLabels': ['Arm 2 (tuvusertib, avelumab)']}, {'name': 'Biopsy Procedure', 'type': 'PROCEDURE', 'otherNames': ['Biopsy', 'BIOPSY_TYPE', 'Bx'], 'description': 'Undergo biopsy', 'armGroupLabels': ['Arm 1 (tuvusertib)', 'Arm 2 (tuvusertib, avelumab)']}, {'name': 'Biospecimen Collection', 'type': 'PROCEDURE', 'otherNames': ['Biological Sample Collection', 'Biospecimen Collected', 'Specimen Collection'], 'description': 'Undergo collection of blood and stool', 'armGroupLabels': ['Arm 1 (tuvusertib)', 'Arm 2 (tuvusertib, avelumab)']}, {'name': 'Computed Tomography', 'type': 'PROCEDURE', 'otherNames': ['CAT', 'CAT Scan', 'Computed Axial Tomography', 'Computerized Axial Tomography', 'Computerized axial tomography (procedure)', 'Computerized Tomography', 'Computerized Tomography (CT) scan', 'CT', 'CT Scan', 'Diagnostic CAT Scan', 'Diagnostic CAT Scan Service Type', 'tomography'], 'description': 'Undergo CT or PET/CT', 'armGroupLabels': ['Arm 1 (tuvusertib)', 'Arm 2 (tuvusertib, avelumab)']}, {'name': 'Magnetic Resonance Imaging', 'type': 'PROCEDURE', 'otherNames': ['Magnetic Resonance', 'Magnetic Resonance Imaging (MRI)', 'Magnetic resonance imaging (procedure)', 'Magnetic Resonance Imaging Scan', 'Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance', 'MR', 'MR Imaging', 'MRI', 'MRI Scan', 'MRIs', 'NMR Imaging', 'NMRI', 'Nuclear Magnetic Resonance Imaging', 'sMRI', 'Structural MRI'], 'description': 'Undergo MRI', 'armGroupLabels': ['Arm 1 (tuvusertib)', 'Arm 2 (tuvusertib, avelumab)']}, {'name': 'Positron Emission Tomography', 'type': 'PROCEDURE', 'otherNames': ['Medical Imaging, Positron Emission Tomography', 'PET', 'PET Scan', 'Positron emission tomography (procedure)', 'Positron Emission Tomography Scan', 'Positron-Emission Tomography', 'PT'], 'description': 'Undergo PET/CT', 'armGroupLabels': ['Arm 1 (tuvusertib)', 'Arm 2 (tuvusertib, avelumab)']}, {'name': 'Tuvusertib', 'type': 'DRUG', 'otherNames': ['ATR Kinase Inhibitor M1774', 'M 1774', 'M-1774', 'M1774'], 'description': 'Given PO', 'armGroupLabels': ['Arm 1 (tuvusertib)', 'Arm 2 (tuvusertib, avelumab)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '92612', 'city': 'Irvine', 'state': 'California', 'country': 'United States', 'facility': 'UCI Health - 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