[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100053708":3},{"organization":4,"outcomesModule":7,"designInfo":88,"detailedDescription":95,"studyPopulation":87,"armGroups":96,"interventions":112,"overallOfficials":87,"centralContacts":124,"locations":130,"responsibleParty":323,"collaborators":87,"id":325,"slug":87,"hasResults":326,"nctId":327,"briefTitle":328,"officialTitle":329,"acronym":330,"eligibilityCriteria":331,"healthyVolunteers":326,"sex":332,"minAge":333,"maxAge":87,"enrollmentInfo":334,"targetDuration":87,"studyType":337,"phases":338,"briefSummary":341,"conditions":342,"keywords":344,"overallStatus":133,"whyStopped":87,"lastUpdateSubmitDate":347,"lastUpdatePostDateStruct":348,"startDateStruct":351,"completionDateStruct":353,"leadSponsor":355,"locationsCount":356},{"fullName":5,"class":6},"AstraZeneca","INDUSTRY",{"primaryOutcomes":8,"secondaryOutcomes":21,"otherOutcomes":87},[9,13,17],{"measure":10,"description":11,"timeFrame":12},"All Modules: Incidence of adverse events (AEs) and serious adverse events (SAEs). To determine the RP2D of AZD3470 as monotherapy and in combination with anticancer agents","Number of participants with AEs and SAEs.","From time of informed consent to 28 days post last dose of study treatment",{"measure":14,"description":15,"timeFrame":16},"Module 1: Incidence of dose-limiting toxicities (DLT)","Incidence of dose-limiting toxicities (DLT) as determined by number of patients with at least 1 dose-limiting toxicity (DLT)","From first dose of study treatment until the end of Cycle 1 (each cycle is 21 days)",{"measure":18,"description":19,"timeFrame":20},"Module 2: Progression Free Survival assessed by the Investigator according to RECIST v1.1","PFS - defined as time from date of randomization until progression per RECIST v1.1 as assessed by the Investigator at local site, or death due to any cause.","From date of randomization up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).",[22,26,29,32,36,40,44,48,51,54,57,60,63,66,69,72,76,80,84],{"measure":23,"description":24,"timeFrame":25},"All modules: Radiological response assessed by the Investigator evaluated according to RECIST v1.1 - ORR (Objective Response Rate)","Proportion of participants who have a complete or partial radiological response as determined by the Investigator according to RECIST v1.1","From date of first dose of AZD3470 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).",{"measure":27,"description":28,"timeFrame":25},"All modules: Radiological response assessed by the Investigator evaluated according to RECIST v1.1 - DoR (Duration of Response)","DoR - the time from date of first documented objective response until date of documented disease progression per Tumor RECIST v1.1 as assessed by the Investigator at local site or death due to any cause.",{"measure":30,"description":31,"timeFrame":25},"All modules: Radiological response assessed by the Investigator evaluated according to RECIST v1.1 - Best percentage change in tumor size","Best percentage change from baseline in TL (target lesion) tumor size is based on the RECIST 1.1. TL measurements as assessed by the Investigator.",{"measure":33,"description":34,"timeFrame":35},"Module 1: Progression Free Survival assessed by the Investigator evaluated according to RECIST v1.1","PFS - defined as time from date of first dose (nonrandomized study parts) or date of randomization (randomized study parts) until progression per RECIST v1.1 as assessed by the Investigator at local site, or death due to any cause.","From date of first dose\u002Frandomization up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).",{"measure":37,"description":38,"timeFrame":39},"All modules: Radiological response assessed by the Investigator evaluated according to RECIST v1.1 - DCR (Disease Control Rate) at 12 weeks","DCR at 12 weeks defined as the percentage of participants who have a CR (complete response) or PR (partial response) or who have SD (stable disease) per RECIST 1.1 as assessed by the Investigator at local site and derived from the raw tumor data for at least 11 weeks after date of first dose to allow for an early assessment within the assessment window.","From date of first dose of AZD3470 up until progression, or the last evaluable assessment in the absence of progression (for each patient this is expected to be measured at 12 weeks).",{"measure":41,"description":42,"timeFrame":43},"All modules: Overall Survival (OS)","Overall Survival (OS) - defined as time from date of first dose (nonrandomized study parts) or date of randomization (randomized study parts) until the date of death due to any cause.","From date of first dose of AZD3470 up until the date of death due to any cause (approximately 2 years).",{"measure":45,"description":46,"timeFrame":47},"Module 1 Endpoints Part A (Dose escalation) Measurement of PK parameters: AUC","Part A (Dose escalation) Measurement of PK parameters: Area under the concentration time curve (AUC).","At predefined intervals throughout the treatment period (for each patient this is expected to be measured up to approximately 4 weeks)",{"measure":49,"description":50,"timeFrame":47},"Module 1 Endpoints Part A (Dose escalation) Measurement of PK parameters: C-max","Part A (Dose escalation) Measurement of PK parameters: Maximum observed plasma concentration of the study drug (C-max).",{"measure":52,"description":53,"timeFrame":47},"Module 1 Endpoints Part A (Dose escalation) Measurement of PK parameters: half life","Part A (Dose escalation) Measurement of PK parameters: Terminal elimination half-life (t 1\u002F2)",{"measure":55,"description":56,"timeFrame":47},"Module 1 Endpoints Part A (Dose escalation) Measurement of PK parameters: Ae (excreted in urine)","Part A (Dose escalation) Measurement of PK parameters: amount of AZD3470 excreted in urine (Ae).",{"measure":58,"description":59,"timeFrame":47},"Module 1 Endpoints Part A (Dose escalation) Measurement of PK parameters: Clr (renal clearance)","Part A (Dose escalation) Measurement of PK parameters: renal clearance (Clr).",{"measure":61,"description":62,"timeFrame":47},"Module 1 Endpoints Part A drug-drug interaction (DDI) - Measurement of PK parameters of Midazolam: Cmax","Part A (DDI)- Plasma geometric mean ratio (Maximum observed plasma concentration of the study drug (C-max)) of Midazolam evaluated with and without AZD3470",{"measure":64,"description":65,"timeFrame":47},"Module 1 Endpoints Part A (DDI) - Measurement of PK parameters of Midazolam: AUC","Part A (DDI) - Plasma geometric mean ratio (Area under the concentration time curve (AUC)) of Midazolam evaluated with and without AZD3470",{"measure":67,"description":68,"timeFrame":47},"Module 1 Endpoints Part A (DDI) - Measurement of PK parameters of Dextromethorphan: Cmax","Part A (DDI)- Plasma geometric mean ratio (Maximum observed plasma concentration of the study drug (C-max)) of Dextromethorphan evaluated with and without AZD3470",{"measure":70,"description":71,"timeFrame":47},"Module 1 Endpoints Part A (DDI) - Measurement of PK parameters of Dextromethorphan: AUC","Part A (DDI) - Plasma geometric mean ratio (Area under the concentration time curve (AUC)) of Dextromethorphan evaluated with and without AZD3470",{"measure":73,"description":74,"timeFrame":75},"Module 1 Endpoints Part A pharmacodynamic backfill cohorts - Measurement of SDMA in tumor.","Part A pharmacodynamic backfill- Percentage change from baseline tumor SDMA as measured by immunohistochemistry.","From screening baseline timepoint to up to four weeks on treatment timepoint.",{"measure":77,"description":78,"timeFrame":79},"Module 2: Time to response (TTR)","The time from date of randomization until the date of first documented objective response, per RECIST 1.1. as assessed by the investigator","From randomization until the date of first documented objective response, per RECIST v1.1 as assessed by the investigator",{"measure":81,"description":82,"timeFrame":83},"Module 2: PK parameters of AZD3470 and Dato-DXd","Measurement of PK parameters:\n\n* Maximum total plasma concentration Cmax\n* Time to maximum concentration Tmax\n* Area under total plasma concentration curve AUC","From C1D1 until EOT\u002F28 Day Follow Up",{"measure":85,"description":86,"timeFrame":83},"Module 2: Presence of ADAs (anti-drug antibody) for Dato-DXd","To evaluate the immunogenicity of Dato-DXd Presence of ADAs (anti-drug antibody) for Dato-DXd",null,{"allocation":89,"interventionModel":90,"interventionModelDescription":91,"primaryPurpose":92,"observationalModel":87,"timePerspective":87,"maskingInfo":93},"NA","SEQUENTIAL","This is a FTiH (first time in human), modular Phase I\u002FIIa, open-label, multi-centre study of AZD3470 as Monotherapy and in Combination with Anti-cancer agents, in participants with MTAP deficient advanced\u002Fmetastatic solid tumors. The study consists of individual modules, each evaluating safety and tolerability of AZD3470 dosed as a monotherapy or in combination with specific treatments. Module 1 describes AZD3470 monotherapy, and will have at least two parts. Part A consisting of dose escalation cohorts and Part B consisting of optimization and expansion cohorts. Module 2 describes AZD3470 in combination with Dato-DXd and will consist of cohorts of AZD3470 in combination with Dato-DXd and a cohort of Dato-DXd as monotherapy","TREATMENT",{"masking":94,"maskingDescription":87,"whoMasked":87},"NONE","This first time in human, open-label, multi-centre study of AZD3470 in participants with advanced or metastatic solid tumors with MTAP deficiency follows a modular design. Module 1 Part A will include the dose escalation cohorts. Part B will include the dose optimization and expansion cohorts. The purpose of the Phase 2 Module 2 is to evaluate the efficacy and safety of AZD3470 in combination with Dato-DXd versus Dato-DXd alone - dose optimization and expansion. New modules for combination treatments may be added in the future based on emerging data.",[97,103,108],{"label":98,"type":99,"description":100,"interventionNames":101},"Module 1: AZD3470 Monotherapy","EXPERIMENTAL","Part A dose escalation and back-fill cohorts and Part B dose optimization and expansion cohorts of varying doses of AZD3470",[102],"Drug: AZD3470",{"label":104,"type":99,"description":105,"interventionNames":106},"Module 2: AZD3470 in combination with Dato-DXd","Varying doses of AZD3470 in combination with Dato-Dxd",[102,107],"Drug: Datopotamab deruxtecan",{"label":109,"type":99,"description":110,"interventionNames":111},"Module 2: Dato-DXd alone","Control arm",[107],[113,118],{"type":114,"name":115,"description":116,"armGroupLabels":117,"otherNames":87},"DRUG","AZD3470","AZD3470 is a novel, potent and selective, second-generation, MTAP-selective, inhibitor of PRMT5.",[98,104],{"type":114,"name":119,"description":120,"armGroupLabels":121,"otherNames":122},"Datopotamab deruxtecan","AZD3470 in combination with Dato-DXd + Dato-Dxd monotherapy",[104,109],[123],"Dato-DXd",[125],{"name":126,"role":127,"phone":128,"phoneExt":87,"email":129},"AstraZeneca Clinical Study Information Center","CONTACT","1-877-240-9479","information.center@astrazeneca.com",[131,145,154,163,172,181,190,199,208,218,228,236,244,253,263,273,281,291,300,305,315],{"facility":132,"status":133,"city":134,"state":135,"zip":136,"country":137,"countryCode":138,"cosmosGeoPoint":139,"geoPoint":144,"contacts":87},"Research Site","RECRUITING","San Francisco","California","94143","United States","US",{"type":140,"coordinates":141},"Point",[142,143],-122.41942,37.77493,{"lat":143,"lon":142},{"facility":132,"status":146,"city":147,"state":135,"zip":148,"country":137,"countryCode":138,"cosmosGeoPoint":149,"geoPoint":153,"contacts":87},"WITHDRAWN","West Hollywood","90048",{"type":140,"coordinates":150},[151,152],-118.36174,34.09001,{"lat":152,"lon":151},{"facility":132,"status":133,"city":155,"state":156,"zip":157,"country":137,"countryCode":138,"cosmosGeoPoint":158,"geoPoint":162,"contacts":87},"New Haven","Connecticut","06510",{"type":140,"coordinates":159},[160,161],-72.92816,41.30815,{"lat":161,"lon":160},{"facility":132,"status":133,"city":164,"state":165,"zip":166,"country":137,"countryCode":138,"cosmosGeoPoint":167,"geoPoint":171,"contacts":87},"Baltimore","Maryland","21231",{"type":140,"coordinates":168},[169,170],-76.61219,39.29038,{"lat":170,"lon":169},{"facility":132,"status":133,"city":173,"state":174,"zip":175,"country":137,"countryCode":138,"cosmosGeoPoint":176,"geoPoint":180,"contacts":87},"Portland","Oregon","97239",{"type":140,"coordinates":177},[178,179],-122.67621,45.52345,{"lat":179,"lon":178},{"facility":132,"status":133,"city":182,"state":183,"zip":184,"country":137,"countryCode":138,"cosmosGeoPoint":185,"geoPoint":189,"contacts":87},"Pittsburgh","Pennsylvania","15232",{"type":140,"coordinates":186},[187,188],-79.99589,40.44062,{"lat":188,"lon":187},{"facility":132,"status":133,"city":191,"state":192,"zip":193,"country":137,"countryCode":138,"cosmosGeoPoint":194,"geoPoint":198,"contacts":87},"Providence","Rhode Island","02903",{"type":140,"coordinates":195},[196,197],-71.41283,41.82399,{"lat":197,"lon":196},{"facility":132,"status":133,"city":200,"state":201,"zip":202,"country":137,"countryCode":138,"cosmosGeoPoint":203,"geoPoint":207,"contacts":87},"Fairfax","Virginia","22031",{"type":140,"coordinates":204},[205,206],-77.30637,38.84622,{"lat":206,"lon":205},{"facility":132,"status":133,"city":209,"state":87,"zip":210,"country":211,"countryCode":212,"cosmosGeoPoint":213,"geoPoint":217,"contacts":87},"Melbourne","3000","Australia","AU",{"type":140,"coordinates":214},[215,216],144.96332,-37.814,{"lat":216,"lon":215},{"facility":132,"status":133,"city":219,"state":87,"zip":220,"country":221,"countryCode":222,"cosmosGeoPoint":223,"geoPoint":227,"contacts":87},"Beijing","100142","China","CN",{"type":140,"coordinates":224},[225,226],116.39723,39.9075,{"lat":226,"lon":225},{"facility":132,"status":133,"city":229,"state":87,"zip":230,"country":221,"countryCode":222,"cosmosGeoPoint":231,"geoPoint":235,"contacts":87},"Chengdu","610041",{"type":140,"coordinates":232},[233,234],104.06667,30.66667,{"lat":234,"lon":233},{"facility":132,"status":133,"city":237,"state":87,"zip":238,"country":221,"countryCode":222,"cosmosGeoPoint":239,"geoPoint":243,"contacts":87},"Shanghai","200433",{"type":140,"coordinates":240},[241,242],121.45806,31.22222,{"lat":242,"lon":241},{"facility":132,"status":245,"city":246,"state":87,"zip":247,"country":221,"countryCode":222,"cosmosGeoPoint":248,"geoPoint":252,"contacts":87},"NOT_YET_RECRUITING","Wuhan","430030",{"type":140,"coordinates":249},[250,251],114.26667,30.58333,{"lat":251,"lon":250},{"facility":132,"status":245,"city":254,"state":87,"zip":255,"country":256,"countryCode":257,"cosmosGeoPoint":258,"geoPoint":262,"contacts":87},"Villejuif","94805","France","FR",{"type":140,"coordinates":259},[260,261],2.35992,48.7939,{"lat":261,"lon":260},{"facility":132,"status":133,"city":264,"state":87,"zip":265,"country":266,"countryCode":267,"cosmosGeoPoint":268,"geoPoint":272,"contacts":87},"Chūōku","104-0045","Japan","JP",{"type":140,"coordinates":269},[270,271],130.67068,33.63867,{"lat":271,"lon":270},{"facility":132,"status":133,"city":274,"state":87,"zip":275,"country":266,"countryCode":267,"cosmosGeoPoint":276,"geoPoint":280,"contacts":87},"Kashiwa","227-8577",{"type":140,"coordinates":277},[278,279],139.97732,35.86224,{"lat":279,"lon":278},{"facility":132,"status":133,"city":282,"state":87,"zip":283,"country":284,"countryCode":285,"cosmosGeoPoint":286,"geoPoint":290,"contacts":87},"Amsterdam","1066CX","Netherlands","NL",{"type":140,"coordinates":287},[288,289],4.88969,52.37403,{"lat":289,"lon":288},{"facility":132,"status":133,"city":292,"state":87,"zip":293,"country":294,"countryCode":87,"cosmosGeoPoint":295,"geoPoint":299,"contacts":87},"Seoul","03080","South Korea",{"type":140,"coordinates":296},[297,298],126.9784,37.566,{"lat":298,"lon":297},{"facility":132,"status":133,"city":292,"state":87,"zip":301,"country":294,"countryCode":87,"cosmosGeoPoint":302,"geoPoint":304,"contacts":87},"06351",{"type":140,"coordinates":303},[297,298],{"lat":298,"lon":297},{"facility":132,"status":133,"city":306,"state":87,"zip":307,"country":308,"countryCode":309,"cosmosGeoPoint":310,"geoPoint":314,"contacts":87},"Barcelona","8035","Spain","ES",{"type":140,"coordinates":311},[312,313],2.15899,41.38879,{"lat":313,"lon":312},{"facility":132,"status":133,"city":316,"state":87,"zip":317,"country":308,"countryCode":309,"cosmosGeoPoint":318,"geoPoint":322,"contacts":87},"Madrid","28027",{"type":140,"coordinates":319},[320,321],-3.70256,40.4165,{"lat":321,"lon":320},{"type":324,"investigatorFullName":87,"investigatorTitle":87,"investigatorAffiliation":87,"oldNameTitle":87,"oldOrganization":87},"SPONSOR","100053708",false,"NCT06130553","A Study of AZD3470, a PRMT5 Inhibitor, Given as Monotherapy and in Combination in Patients With MTAP Deficient Advanced\u002FMetastatic Solid Tumors","PRIMROSE: A Modular Phase I\u002FIIa, Multi-centre, Dose Escalation, and Expansion Study of AZD3470, a MTA Cooperative PRMT5 Inhibitor, as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced\u002FMetastatic Solid Tumors That Are MTAP Deficient","PRIMROSE","Inclusion Criteria (All Modules) Participants are ≥ 18 years (or the legal age of consent in the jurisdiction) at the time of signing the informed consent form.\n\nParticipants are able to provide written informed consent and are willing and able to comply with study procedures.\n\nParticipants are willing to provide archival and\u002For newly obtained (baseline) tumor tissue for central testing, including required biomarker assessment(s) (and any module-specific biomarker requirements).\n\nParticipants have tumors meeting the protocol-defined MTAP-deficiency requirement, based on acceptable prior testing and\u002For central testing per protocol.\n\nParticipants have received prior systemic therapy appropriate for the tumor type and disease stage and have disease progression on or after prior therapy; participants must have had ≥ 1 prior line of systemic treatment in the recurrent\u002Fmetastatic (advanced) setting.\n\nParticipants have ECOG performance status 0-1. Participants have life expectancy ≥ 12 weeks, in the opinion of the Investigator.\n\nParticipants have measurable disease per RECIST v1.1. Participants have adequate organ and bone marrow function per protocol-defined laboratory\u002Fassessment criteria.\n\nParticipants have a treatment-free interval ≥ 3 weeks from prior anticancer therapy before starting study drug (with any additional protocol-defined washout requirements for certain therapies\u002Fprocedures).\n\nContraception use by men and women is consistent with local regulations and protocol-defined requirements.\n\nAdditional Inclusion Criteria (Module 2: Non-squamous NSCLC) Participants have histologically or cytologically confirmed non-squamous NSCLC, Stage IIIB\u002FIIIC not amenable to curative therapy or Stage IV.\n\nParticipants have documented radiographic extracranial disease progression while on or after the most recent treatment regimen for advanced\u002Fmetastatic NSCLC (CNS-only progression is not eligible).\n\nNSCLC of mixed histology is allowed if not predominantly squamous; no small cell or large cell neuroendocrine components.\n\nParticipants meet one of the following:\n\nTumor has a documented EGFR alteration eligible for EGFR-directed therapy (per protocol-defined criteria) and the participant has received prior systemic therapy appropriate for EGFR-altered advanced\u002Fmetastatic NSCLC (per protocol), OR Tumor is negative for EGFR alterations eligible for EGFR-directed therapy, has no other known actionable genomic alterations for which locally approved\u002Favailable targeted therapies exist (per protocol-defined criteria), meets any additional protocol-required biomarker criteria for this cohort (as applicable), and the participant has received prior systemic therapy appropriate for non-actionable-alteration advanced\u002Fmetastatic NSCLC (per protocol).\n\nExclusion Criteria (All Modules) Participants have spinal cord compression, or symptomatic and unstable brain metastases, leptomeningeal disease, or primary CNS malignancy. Participants with asymptomatic, radiographically stable brain metastases who do not require steroids (or who have completed definitive therapy and are neurologically stable off steroids, per protocol) may be eligible.\n\nParticipants have a history of allogeneic organ transplantation. Participants have any clinically significant abnormal laboratory finding or severe and uncontrolled medical condition that, in the Investigator's opinion, makes participation unsafe, including active infection requiring systemic treatment.\n\nParticipants have clinically significant cardiovascular disease or risk factors (including reduced LVEF, cardiomyopathy, clinically active cardiovascular disease, recent major ischemic events or revascularization procedures, uncontrolled angina, severe valvular disease, uncontrolled hypertension, clinically significant heart failure, or recent stroke\u002FTA clinically significant ECG abnormalities, prolonged QTc, or conditions\u002Fmedications that increase risk of QTc prolongation or arrhythmic events)..\n\nParticipants require therapeutic anticoagulation for treatment of acute thromboembolic events, per protocol.\n\nParticipants have active hepatitis B or hepatitis C infection (including detectable viral load, per protocol-defined testing).\n\nParticipants have known HIV infection. Participants have current ILD\u002Fpneumonitis, or a history of (non-infectious) ILD\u002Fpneumonitis requiring systemic steroids or supplemental oxygen, or suspected ILD\u002Fpneumonitis that cannot be ruled out by screening imaging.\n\nParticipants have active gastrointestinal disease, malabsorption, or other GI condition\u002Fsurgery that would significantly interfere with oral drug absorption or tolerability.\n\nParticipants have a history of another primary malignancy. Participants have unresolved clinically significant toxicity from prior anticancer therapy (typically Grade ≥ 2).\n\nParticipants have had prior treatment with a PRMT5 inhibitor Participants are pregnant, breastfeeding, or intend to become pregnant during study participation.\n\nAdditional Exclusion Criteria (Module 2 Only) Participants have inaccessible veins and\u002For inability to place required venous access (e.g., port), per Investigator judgment.\n\nParticipants have contraindication to required CNS imaging (brain MRI preferred or CT with contrast).\n\nParticipants have clinically significant corneal disease. Participants have known active tuberculosis infection, per clinical evaluation and local practice.\n\nParticipants have significant third-space fluid (e.g., pleural effusion\u002Fascites) not amenable to required repeated drainage, per Investigator judgment.\n\nParticipants have severe pulmonary function compromise due to intercurrent pulmonary illness (e.g., severe COPD\u002Fasthma\u002Frestrictive lung disease, recent pulmonary embolism), per protocol.\n\nParticipants have recent radiotherapy that does not meet protocol-defined washout requirements and\u002For ongoing radiation-related toxicities requiring corticosteroids.\n\nParticipants have had prior treatment with protocol-prohibited anticancer therapies.","ALL","18 Years",{"count":335,"type":336},334,"ESTIMATED","INTERVENTIONAL",[339,340],"PHASE1","PHASE2","This is a first time in human (FTiH) Phase I\u002FIIa, open-label, multi-centre study of AZD3470 in participants with advanced or metastatic solid tumors with MTAP deficiency. The study consists of several study modules, evaluating the safety, tolerability, pharmacokinetic (PK), pharmacodynamics, and preliminary efficacy of AZD3470 as monotherapy or in combination with other anti-cancer agents.",[343],"Advanced Solid Tumors That Are MTAP Deficient",[345,346],"solid tumor","MTAP deficient","2026-07-10",{"date":349,"type":350},"2026-07-13","ACTUAL",{"date":352,"type":350},"2024-01-18",{"date":354,"type":336},"2028-12-04",{"name":5,"class":6},21]