{"id":"https://openalex.org/W4286298043","doi":"https://doi.org/10.1200/jco.2022.40.16_suppl.tps3173","title":"Phase 1/2 dose escalation study of NUV-422, a potent inhibitor of cyclin-dependent kinases 2, 4, and 6, in recurrent or refractory (r/r) high-grade gliomas (HGG) and solid tumors.","display_name":"Phase 1/2 dose escalation study of NUV-422, a potent inhibitor of cyclin-dependent kinases 2, 4, and 6, in recurrent or refractory (r/r) high-grade gliomas (HGG) and solid tumors.","publication_year":2022,"publication_date":"2022-06-01","ids":{"openalex":"https://openalex.org/W4286298043","doi":"https://doi.org/10.1200/jco.2022.40.16_suppl.tps3173"},"language":"en","primary_location":{"id":"doi:10.1200/jco.2022.40.16_suppl.tps3173","doi":"https://doi.org/10.1200/jco.2022.40.16_suppl.tps3173","is_oa":false,"landing_page_url":"https://doi.org/10.1200/jco.2022.40.16_suppl.tps3173","pdf_url":null,"source":{"id":"https://openalex.org/S15137598","display_name":"Journal of Clinical Oncology","issn_l":"0732-183X","issn":["0732-183X","1527-7755"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical Oncology","raw_type":"journal-article"},"volume":null,"type":"conference-abstract","is_traditional":false,"indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5021656597","display_name":"Patrick Yung Wen","orcid":"https://orcid.org/0000-0002-0774-7700","observed_orcids":["https://orcid.org/0000-0002-0774-7700","https://orcid.org/0000-0003-3224-3042","https://orcid.org/0000-0002-2452-0540"]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]},{"id":"https://openalex.org/I4210161994","display_name":"Dana-Farber Brigham Cancer Center","ror":"https://ror.org/05rgrbr06","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I121934306","https://openalex.org/I1283280774","https://openalex.org/I4210117453","https://openalex.org/I4210161994","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Patrick Y. Wen","raw_affiliation_strings":["Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, MA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, MA;","institution_ids":["https://openalex.org/I136199984","https://openalex.org/I4210161994"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5031165814","display_name":"Jordi Ahnert Rodon","orcid":"https://orcid.org/0000-0001-6467-3632","observed_orcids":["https://orcid.org/0000-0001-6467-3632","https://orcid.org/0000-0003-2234-5248"]},"institutions":[{"id":"https://openalex.org/I1343551460","display_name":"The University of Texas MD Anderson Cancer Center","ror":"https://ror.org/04twxam07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1343551460"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jordi Rodon Ahnert","raw_affiliation_strings":["Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX;","institution_ids":["https://openalex.org/I1343551460"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5090977453","display_name":"John D. Powderly","orcid":"https://orcid.org/0000-0002-7608-0380","observed_orcids":["https://orcid.org/0000-0002-7608-0380"]},"institutions":[{"id":"https://openalex.org/I4210093858","display_name":"Carolina BioOncology Institute","ror":"https://ror.org/00htvrc11","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210093858"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"John D. Powderly","raw_affiliation_strings":["Carolina BioOncology Institute, Huntersville, NC;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Carolina BioOncology Institute, Huntersville, NC;","institution_ids":["https://openalex.org/I4210093858"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5047608444","display_name":"Howard Colman","orcid":"https://orcid.org/0000-0002-4027-7317","observed_orcids":["https://orcid.org/0000-0002-4027-7317"]},"institutions":[{"id":"https://openalex.org/I223532165","display_name":"University of Utah","ror":"https://ror.org/03r0ha626","country_code":"US","type":"education","lineage":["https://openalex.org/I223532165"]},{"id":"https://openalex.org/I2801159745","display_name":"Huntsman Cancer Institute","ror":"https://ror.org/03v7tx966","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I2801159745","https://openalex.org/I4210148268"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Howard Colman","raw_affiliation_strings":["Huntsman Cancer Institute, University of Utah, Salt Lake City, UT;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Huntsman Cancer Institute, University of Utah, Salt Lake City, UT;","institution_ids":["https://openalex.org/I223532165","https://openalex.org/I2801159745"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5012211904","display_name":"Shannon L. Matheny","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Shannon L. Matheny","raw_affiliation_strings":["Ortho Biotech, Los Angeles, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Ortho Biotech, Los Angeles, CA;","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5011711765","display_name":"Anthony A. Golsorkhi","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I183934855","display_name":"Genentech","ror":"https://ror.org/04gndp242","country_code":"US","type":"company","lineage":["https://openalex.org/I118019719","https://openalex.org/I129302853","https://openalex.org/I183934855"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Anthony A. Golsorkhi","raw_affiliation_strings":["Genentech, South San Francisco, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Genentech, South San Francisco, CA;","institution_ids":["https://openalex.org/I183934855"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5073955009","display_name":"Teeru Bihani","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210093176","display_name":"Radius Health (United States)","ror":"https://ror.org/00m2x3q29","country_code":"US","type":"company","lineage":["https://openalex.org/I4210093176"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Teeru Bihani","raw_affiliation_strings":["Radius Health, Inc., Waltham, MA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Radius Health, Inc., Waltham, MA;","institution_ids":["https://openalex.org/I4210093176"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100456445","display_name":"Yan Zhang","orcid":"https://orcid.org/0000-0003-4647-4853","observed_orcids":["https://orcid.org/0000-0003-4647-4853"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Yan Zhang","raw_affiliation_strings":["Nuvation Bio, San Francisco, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Nuvation Bio, San Francisco, CA;","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5042155392","display_name":"Thomas Joseph Kaley","orcid":"https://orcid.org/0000-0002-2540-8518","observed_orcids":["https://orcid.org/0000-0002-2540-8518"]},"institutions":[{"id":"https://openalex.org/I1334819555","display_name":"Memorial Sloan Kettering Cancer Center","ror":"https://ror.org/02yrq0923","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1334819555"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Thomas Joseph Kaley","raw_affiliation_strings":["Memorial Sloan Kettering Cancer Center, New York, NY;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Memorial Sloan Kettering Cancer Center, New York, NY;","institution_ids":["https://openalex.org/I1334819555"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":9,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":4,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"40","issue":"16_suppl","first_page":"TPS3173","last_page":"TPS3173"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10129","display_name":"Glioma Diagnosis and Treatment","score":0.8163999915122986,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10129","display_name":"Glioma Diagnosis and Treatment","score":0.8163999915122986,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T12829","display_name":"Advanced Breast Cancer Therapies","score":0.14830000698566437,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10952","display_name":"PI3K/AKT/mTOR signaling in cancer","score":0.0035000001080334187,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/cyclin-dependent-kinases","display_name":"cyclin-dependent kinases","score":0.8809999823570251},{"id":"https://openalex.org/keywords/glioblastoma","display_name":"glioblastoma","score":0.9909999966621399},{"id":"https://openalex.org/keywords/hr-her2-metastatic-breast-cancer","display_name":"HR+/HER2- metastatic breast cancer","score":0.8230000138282776},{"id":"https://openalex.org/keywords/metastatic-castration-resistant-prostate-cancer","display_name":"metastatic castration-resistant prostate cancer","score":0.9210000038146973},{"id":"https://openalex.org/keywords/cdk4-6-inhibitor-resistance","display_name":"CDK4/6 inhibitor resistance","score":0.8349999785423279},{"id":"https://openalex.org/keywords/patient-derived-xenografts","display_name":"patient-derived xenografts","score":0.7289999723434448},{"id":"https://openalex.org/keywords/pharmacokinetics","display_name":"pharmacokinetics","score":0.656000018119812},{"id":"https://openalex.org/keywords/pharmacodynamics","display_name":"pharmacodynamics","score":0.9380000233650208},{"id":"https://openalex.org/keywords/blood-brain-barrier-penetration","display_name":"blood-brain barrier penetration","score":0.7009999752044678}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.8597093224525452},{"id":"https://openalex.org/C124320809","wikidata":"https://www.wikidata.org/wiki/Q46292","display_name":"Cyclin-dependent kinase","level":4,"score":0.6546028256416321},{"id":"https://openalex.org/C2778375690","wikidata":"https://www.wikidata.org/wiki/Q7814214","display_name":"Tolerability","level":3,"score":0.6107951402664185},{"id":"https://openalex.org/C199649820","wikidata":"https://www.wikidata.org/wiki/Q14911762","display_name":"Cyclin-dependent kinase 6","level":5,"score":0.5206679105758667},{"id":"https://openalex.org/C2780192828","wikidata":"https://www.wikidata.org/wiki/Q181257","display_name":"Prostate cancer","level":3,"score":0.4924555718898773},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.48236507177352905},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.47272342443466187},{"id":"https://openalex.org/C111113717","wikidata":"https://www.wikidata.org/wiki/Q725307","display_name":"Pharmacodynamics","level":3,"score":0.4713073670864105},{"id":"https://openalex.org/C142424586","wikidata":"https://www.wikidata.org/wiki/Q7307572","display_name":"Refractory (planetary science)","level":2,"score":0.46014177799224854},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.444699227809906},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.44463518261909485},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.39442282915115356},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.3656849265098572},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.36547064781188965},{"id":"https://openalex.org/C29537977","wikidata":"https://www.wikidata.org/wiki/Q188941","display_name":"Cell cycle","level":3,"score":0.3078274130821228},{"id":"https://openalex.org/C197934379","wikidata":"https://www.wikidata.org/wiki/Q2047938","display_name":"Adverse effect","level":2,"score":0.1278720498085022},{"id":"https://openalex.org/C87355193","wikidata":"https://www.wikidata.org/wiki/Q411","display_name":"Astrobiology","level":1,"score":0.0},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.0},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.0},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1200/jco.2022.40.16_suppl.tps3173","doi":"https://doi.org/10.1200/jco.2022.40.16_suppl.tps3173","is_oa":false,"landing_page_url":"https://doi.org/10.1200/jco.2022.40.16_suppl.tps3173","pdf_url":null,"source":{"id":"https://openalex.org/S15137598","display_name":"Journal of Clinical Oncology","issn_l":"0732-183X","issn":["0732-183X","1527-7755"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical Oncology","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.9940000176429749}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4206510785","https://openalex.org/W4295817737","https://openalex.org/W2157005154","https://openalex.org/W4416141060","https://openalex.org/W4393093894","https://openalex.org/W2900039916","https://openalex.org/W4389242120","https://openalex.org/W6967773739","https://openalex.org/W4379282886","https://openalex.org/W3167626185"],"abstract_inverted_index":{"TPS3173":[0],"Background:":[1],"CDKs":[2],"that":[3,92],"govern":[4],"the":[5,9,198,227,312],"G1-S":[6],"transition":[7],"of":[8,54,101,127,137,194,218,295,353,387],"cell":[10,104],"cycle":[11],"(CDK2,":[12],"CDK4":[13],"and":[14,39,108,134,192,196,215,266,299,344,361,381],"CDK6)":[15],"are":[16],"deregulated":[17],"in":[18,23,31,36,46,62,85,106,112,121,151,163,221,358,373,379,383],"many":[19],"cancers.":[20,64],"CDK2":[21],"expression,":[22],"particular,":[24],"is":[25,66,146,229,283,364],"associated":[26,82],"with":[27,74,83,165,274,385],"worse":[28],"overall":[29,300],"survival":[30],"glioblastoma":[32],"(GB),":[33],"disease-free":[34],"recurrence":[35],"prostate":[37,138],"cancer,":[38],"resistance":[40],"to":[41,132,141,157,188,212,311,339,349,375],"approved":[42],"CDK4/6":[43],"inhibitors":[44],"(CDK4/6i)":[45],"breast":[47],"cancer.":[48],"These":[49],"provide":[50],"rationale":[51],"for":[52,345],"inhibition":[53],"CDK2/4/6":[55],"as":[56],"a":[57,67,79,147,185,208],"potential":[58],"novel":[59],"therapeutic":[60],"strategy":[61],"these":[63],"NUV-422":[65,93,116,160,195,220,351,367],"potent":[68],"(low":[69],"nM)":[70],"small":[71],"molecule":[72],"CDK2/4/6i":[73],"limited":[75],"activity":[76,111,120],"against":[77],"CDK1,":[78],"target":[80],"potentially":[81],"toxicities":[84],"other":[86],"CDKi.":[87],"Preclinical":[88],"studies":[89,378],"have":[90],"shown":[91],"has":[94],"favorable":[95],"blood-brain":[96],"barrier":[97],"penetration,":[98],"inhibited":[99],"growth":[100],"multiple":[102,122],"glioma":[103],"lines":[105],"vitro,":[107],"exhibited":[109,118],"antitumor":[110,119],"GB":[113,223],"xenograft":[114,124],"models.":[115],"also":[117,206,370],"patient-derived":[123],"(PDX)":[125],"models":[126,136],"HR+":[128,172,254,271],"HER2-":[129,173,255,272],"mBC":[130,256,273,318,380],"resistant":[131,140],"CDK4/6i,":[133],"PDX":[135],"cancer":[139],"anti-androgens.":[142],"Methods:":[143],"NUV-422-02":[144],"(NCT04541225)":[145],"phase":[148,200,234],"1/2,":[149],"first":[150],"human,":[152],"open":[153],"label,":[154],"multicenter":[155],"study":[156],"evaluate":[158,189,243,253,264,270],"single-agent":[159],"(given":[161],"orally)":[162],"patients":[164],"advanced":[166],"solid":[167],"tumors":[168],"(r/r":[169],"HGG,":[170],"r/r":[171,176],"mBC,":[174],"or":[175,321,333],"mCRPC).":[177],"The":[178,278,366],"Ph":[179,204,279],"1":[180,205,241],"dose":[181,202,362],"escalation":[182,363],"will":[183,238,242,252,263,269,304,336,369],"use":[184],"3+3":[186],"design":[187],"safety,":[190,341],"tolerability,":[191],"PK":[193,214],"establish":[197],"recommended":[199],"2":[201,235,251,280],"(RP2D).":[203],"includes":[207],"randomized":[209],"surgical":[210],"substudy":[211],"characterize":[213,350],"pharmacodynamics":[216],"(PD)":[217],"preoperative":[219],"resected":[222],"tumor":[224,313,334],"tissue.":[225],"After":[226],"RP2D":[228],"identified,":[230],"parallel":[231],"enrollment":[232],"into":[233],"expansion":[236],"cohorts":[237],"begin.":[239],"Cohort":[240,250,261,267],"isocitrate":[244],"dehydrogenase":[245],"wild":[246],"type":[247,314],"(IDH-WT)":[248],"GB.":[249],"(without":[257],"active":[258,275],"brain":[259,276],"metastases);":[260],"3":[262],"mCRPC;":[265],"4":[268],"metastases.":[277],"primary":[281],"endpoint":[282],"objective":[284],"response":[285,308],"rate.":[286],"Secondary":[287],"efficacy":[288],"endpoints":[289],"include":[290,376],"clinical":[291],"benefit":[292],"rate,":[293],"duration":[294],"response,":[296],"progression-free":[297],"survival,":[298],"survival.":[301],"Response":[302],"assessments":[303],"be":[305,337,371],"based":[306],"on":[307],"criteria":[309],"appropriate":[310],"(HGG":[315],"[RANO];":[316],"HR+HER2-":[317],"[RECIST":[319,325],"1.1":[320],"RANO-Brain":[322],"Metastases];":[323],"mCRPC":[324,382],"1.1,":[326],"PCWG3,":[327],"prostate-specific":[328],"antigen":[329],"decrease]).":[330],"Blood,":[331],"urine,":[332],"tissue":[335],"obtained":[338],"assess":[340],"PK,":[342],"PD,":[343],"additional":[346,377],"exploratory":[347],"analyses":[348],"mechanism":[352],"action.":[354],"Enrollment":[355],"was":[356],"initiated":[357],"December":[359],"2020,":[360],"ongoing.":[365],"program":[368],"expanded":[372],"2022":[374],"combination":[384],"standard":[386],"care":[388],"treatments.":[389],"Clinical":[390],"trial":[391],"information:":[392],"NCT04541225.":[393]},"counts_by_year":[{"year":2025,"cited_by_count":1},{"year":2024,"cited_by_count":3}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2022-07-21T00:00:00"}