{"id":"https://openalex.org/W2554471213","doi":"https://doi.org/10.1182/blood.v120.21.203.203","title":"A Phase 1b Dose-Escalation Study of Split-Dose Oprozomib (ONX0912) in Patients with Hematologic Malignancies","display_name":"A Phase 1b Dose-Escalation Study of Split-Dose Oprozomib (ONX0912) in Patients with Hematologic Malignancies","publication_year":2012,"publication_date":"2012-11-16","ids":{"openalex":"https://openalex.org/W2554471213","doi":"https://doi.org/10.1182/blood.v120.21.203.203","mag":"2554471213"},"language":"en","primary_location":{"id":"doi:10.1182/blood.v120.21.203.203","doi":"https://doi.org/10.1182/blood.v120.21.203.203","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v120.21.203.203","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"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/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"},"volume":null,"type":"article","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/A5049400849","display_name":"Michael Robert Savona","orcid":"https://orcid.org/0000-0003-3763-5504","observed_orcids":["https://orcid.org/0000-0003-3763-5504"]},"institutions":[{"id":"https://openalex.org/I4210100810","display_name":"Sarah Cannon","ror":"https://ror.org/014t21j89","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210100810"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Michael R. Savona","raw_affiliation_strings":["Sarah Cannon Research Institute, Nashville, TN, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Sarah Cannon Research Institute, Nashville, TN, USA,","institution_ids":["https://openalex.org/I4210100810"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5050961257","display_name":"Jes\u00fas G. Berdeja","orcid":"https://orcid.org/0000-0003-4362-0376","observed_orcids":["https://orcid.org/0000-0003-4362-0376"]},"institutions":[{"id":"https://openalex.org/I4210100810","display_name":"Sarah Cannon","ror":"https://ror.org/014t21j89","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210100810"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jesus G. Berdeja","raw_affiliation_strings":["Sarah Cannon Research Institute, Nashville, TN, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Sarah Cannon Research Institute, Nashville, TN, USA,","institution_ids":["https://openalex.org/I4210100810"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5087463763","display_name":"Sang Hyuck Lee","orcid":"https://orcid.org/0000-0002-5610-033X","observed_orcids":["https://orcid.org/0000-0002-5610-033X"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Susan J Lee","raw_affiliation_strings":["Onyx Pharmaceuticals, Inc., South San Francisco, CA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Onyx Pharmaceuticals, Inc., South San Francisco, CA, USA,","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5071375201","display_name":"Hansen L. Wong","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Hansen Wong","raw_affiliation_strings":["Onyx Pharmaceuticals, Inc., South San Francisco, CA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Onyx Pharmaceuticals, Inc., South San Francisco, CA, USA,","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5073789192","display_name":"Ju RueyJiuan Lee","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Ju RueyJiuan Lee","raw_affiliation_strings":["Onyx Pharmaceuticals, Inc., South San Francisco, CA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Onyx Pharmaceuticals, Inc., South San Francisco, CA, USA,","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5111783900","display_name":"Heidi H. Gillenwater","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Heidi H. Gillenwater","raw_affiliation_strings":["Onyx Pharmaceuticals, Inc., South San Francisco, CA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Onyx Pharmaceuticals, Inc., South San Francisco, CA, USA,","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5023752321","display_name":"David Samuel DiCapua Siegel","orcid":"https://orcid.org/0000-0002-3604-2574","observed_orcids":["https://orcid.org/0000-0002-3604-2574"]},"institutions":[{"id":"https://openalex.org/I1324520350","display_name":"Hackensack University Medical Center","ror":"https://ror.org/008zj0x80","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1324520350"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David S. Siegel","raw_affiliation_strings":["John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA","institution_ids":["https://openalex.org/I1324520350"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5049400849","https://openalex.org/A5071375201","https://openalex.org/A5073789192","https://openalex.org/A5087463763"],"corresponding_institution_ids":["https://openalex.org/I4210100810"],"apc_list":{"value":5500,"currency":"USD","value_usd":5500},"apc_paid":null,"fwci":1.1546,"has_fulltext":false,"cited_by_count":9,"citation_normalized_percentile":{"value":0.77128602,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":98},"biblio":{"volume":"120","issue":"21","first_page":"203","last_page":"203"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11041","display_name":"Ubiquitin and proteasome pathways","score":0.41190001368522644,"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"}},"topics":[{"id":"https://openalex.org/T11041","display_name":"Ubiquitin and proteasome pathways","score":0.41190001368522644,"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"}},{"id":"https://openalex.org/T10649","display_name":"Multiple Myeloma Research and Treatments","score":0.3862000107765198,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"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/T12534","display_name":"Protein Degradation and Inhibitors","score":0.07109999656677246,"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/oprozomib","display_name":"oprozomib","score":0.9760000109672546},{"id":"https://openalex.org/keywords/proteasome-inhibitors","display_name":"proteasome inhibitors","score":0.8080000281333923},{"id":"https://openalex.org/keywords/hematologic-malignancies","display_name":"hematologic malignancies","score":0.9860000014305115},{"id":"https://openalex.org/keywords/maximum-tolerated-dose","display_name":"maximum tolerated dose","score":0.8669999837875366},{"id":"https://openalex.org/keywords/dose-limiting-toxicity","display_name":"dose-limiting toxicity","score":0.8529999852180481},{"id":"https://openalex.org/keywords/gastrointestinal-side-effects","display_name":"gastrointestinal adverse effects","score":0.7799999713897705},{"id":"https://openalex.org/keywords/diarrhea","display_name":"diarrhea","score":0.734000027179718},{"id":"https://openalex.org/keywords/abdominal-pain","display_name":"abdominal pain","score":0.46000000834465027},{"id":"https://openalex.org/keywords/neutropenia","display_name":"neutropenia","score":0.5360000133514404},{"id":"https://openalex.org/keywords/thrombocytopenia","display_name":"thrombocytopenia","score":0.734000027179718},{"id":"https://openalex.org/keywords/pharmacokinetics","display_name":"pharmacokinetics","score":0.609000027179718},{"id":"https://openalex.org/keywords/pharmacodynamics","display_name":"pharmacodynamics","score":0.8640000224113464},{"id":"https://openalex.org/keywords/safety-and-tolerability","display_name":"safety and tolerability","score":0.6489999890327454}],"concepts":[{"id":"https://openalex.org/C2778375690","wikidata":"https://www.wikidata.org/wiki/Q7814214","display_name":"Tolerability","level":3,"score":0.7376133799552917},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.730303943157196},{"id":"https://openalex.org/C2777334693","wikidata":"https://www.wikidata.org/wiki/Q659446","display_name":"Maximum tolerated dose","level":3,"score":0.6751160621643066},{"id":"https://openalex.org/C2777288759","wikidata":"https://www.wikidata.org/wiki/Q4164182","display_name":"Dosing","level":2,"score":0.6658386588096619},{"id":"https://openalex.org/C2780108899","wikidata":"https://www.wikidata.org/wiki/Q15366934","display_name":"Carfilzomib","level":4,"score":0.6618524193763733},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.6382545828819275},{"id":"https://openalex.org/C111113717","wikidata":"https://www.wikidata.org/wiki/Q725307","display_name":"Pharmacodynamics","level":3,"score":0.6289160847663879},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.5214314460754395},{"id":"https://openalex.org/C197934379","wikidata":"https://www.wikidata.org/wiki/Q2047938","display_name":"Adverse effect","level":2,"score":0.5137306451797485},{"id":"https://openalex.org/C142424586","wikidata":"https://www.wikidata.org/wiki/Q7307572","display_name":"Refractory (planetary science)","level":2,"score":0.4898376166820526},{"id":"https://openalex.org/C2780580376","wikidata":"https://www.wikidata.org/wiki/Q186889","display_name":"Nausea","level":2,"score":0.4238553047180176},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.4117574989795685},{"id":"https://openalex.org/C2778367456","wikidata":"https://www.wikidata.org/wiki/Q7251235","display_name":"Proteasome inhibitor","level":3,"score":0.35412439703941345},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.3450550436973572},{"id":"https://openalex.org/C2776364478","wikidata":"https://www.wikidata.org/wiki/Q467635","display_name":"Multiple myeloma","level":2,"score":0.20985782146453857},{"id":"https://openalex.org/C87355193","wikidata":"https://www.wikidata.org/wiki/Q411","display_name":"Astrobiology","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}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood.v120.21.203.203","doi":"https://doi.org/10.1182/blood.v120.21.203.203","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v120.21.203.203","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"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/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.98580002784729,"display_name":"Good health and well-being"}],"study_designs":[{"id":"https://openalex.org/study-designs/clinical-trial","display_name":"Clinical Trial"}],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2965930384","https://openalex.org/W302431027","https://openalex.org/W2913703682","https://openalex.org/W2480588840","https://openalex.org/W2291965619","https://openalex.org/W2980939983","https://openalex.org/W2537108996","https://openalex.org/W2980484814","https://openalex.org/W2979502983","https://openalex.org/W2980935375"],"abstract_inverted_index":{"Abstract":[0,1],"203":[2],"Background:":[3],"Oprozomib":[4,619],"(OPZ,":[5],"formerly":[6],"ONX":[7],"0912),":[8],"a":[9,35,71,149,153,247,258,500,529],"structural":[10],"analog":[11],"of":[12,47,70,110,133,148,172,197,212,235,249,260,263,301,327,361,419,447,472,483,486,508],"carfilzomib":[13],"(CFZ),":[14],"is":[15,34,87,102,142,187,191,227,238,600,620,630],"an":[16,43,103,170],"orally":[17],"bioavailable,":[18],"next-generation":[19],"proteasome":[20,40,432,565],"inhibitor":[21],"being":[22],"evaluated":[23],"in":[24,51,95,112,179,182,206,210,283,304,316,322,344,350,366,368,378,436,516,532,537,589,610,621],"hematologic":[25,98,115,540,613,627],"malignancies":[26,628],"and":[27,38,124,126,138,216,243,294,312,319,386,411,439,463,510,513,546,629],"solid":[28,56],"tumors.":[29],"Similar":[30],"to":[31,68,121,127,376,399,444,457,505,558],"CFZ,":[32],"OPZ":[33,50,89,111,141,392,523,577],"potent,":[36],"selective,":[37],"irreversible":[39],"inhibitor.":[41],"In":[42],"earlier":[44],"dose-escalation":[45,108,158],"study":[46,85,109,135],"once-daily":[48],"(QD)":[49],"patients":[52,96,113,202,237,269,352,367,380,415,474,517,538,611],"with":[53,74,97,114,169,177,265,310,333,460,494,518,539,569,602,612],"advanced":[54],"refractory":[55],"tumors,":[57],"the":[58,75,92,129,134,207,213,284,307,338,369,382,397,420,442,445,448,467,573,584,598,608,634],"maximum":[59],"tolerated":[60,527],"dose":[61,356,384,401,469,575,587],"(MTD)":[62],"was":[63,161,277,337,427,434,480,524,567],"150":[64],"mg":[65,165,167,287,562],"QD,":[66],"leading":[67],"exploration":[69],"split-dose":[72,93,530],"schedule":[73,94,531],"drug":[76],"administered":[77,90,143],"twice":[78],"daily":[79,423,450],"(BID).":[80],"The":[81,117,232,325],"present":[82],"phase":[83,105,534,604],"1":[84,281,347,492,511,514,535,623],"(NCT01416428)":[86],"evaluating":[88],"using":[91,152,528],"malignancies.":[99,116,541,614],"Methods:":[100],"This":[101],"ongoing,":[104],"1b,":[106],"open-label,":[107],"primary":[118],"objectives":[119,132],"are":[120,475],"evaluate":[122],"safety":[123],"tolerability":[125],"determine":[128],"MTD.":[130],"Secondary":[131],"include":[136],"pharmacokinetic":[137],"pharmacodynamic":[139],"analyses.":[140],"PO":[144],"on":[145],"days":[146],"1\u20135":[147],"14-day":[150],"cycle":[151],"standard":[154],"3":[155,157,209,292,351,371,506,586],"+":[156],"scheme.":[159],"Treatment":[160],"initiated":[162],"at":[163,229,354,381,466,554,572,607],"120":[164],"(60":[166],"BID),":[168],"interval":[171],"4\u20136":[173],"h":[174],"between":[175],"doses,":[176,490],"escalation":[178,594],"30-mg":[180],"increments":[181],"successive":[183],"cohorts":[184],"until":[185,597],"MTD":[186,549,599,609],"determined.":[188],"Tumor":[189],"response":[190],"assessed":[192],"by":[193,279,633],"investigator.":[194],"Results:":[195],"As":[196],"June":[198],"15,":[199],"2012,":[200],"9":[201,473],"have":[203,223,256,271,389],"been":[204,224,390,552],"enrolled":[205],"study,":[208],"each":[211,314,355],"120-mg,":[214],"150-mg,":[215],"180-mg":[217,285,383,400,468],"dosing":[218,372,406,418],"cohorts.":[219,373],"No":[220],"dose-limiting":[221],"toxicities":[222],"observed.":[225],"Enrollment":[226],"ongoing":[228],"210":[230],"mg/day.":[231],"median":[233,248,259],"age":[234],"all":[236,489],"67":[239],"years":[240],"(range":[241,253],"53\u221281)":[242],"prior":[244,503],"therapies":[245],"included":[246],"4":[250,268],"chemotherapy":[251],"regimens":[252],"2\u22128).":[254],"Patients":[255,403],"received":[257,272],"5":[261],"cycles":[262],"treatment":[264],"OPZ,":[266],"including":[267,491],"who":[270,498],"\u22656":[273],"cycles.":[274],"Dose":[275,593],"reduction":[276],"required":[278],"only":[280,339],"patient":[282,493],"(90":[286,561],"BID)":[288],"group":[289],"for":[290,477,626,636],"Grade":[291,302,340],"diarrhea":[293,311],"abdominal":[295],"pain.":[296],"Gastrointestinal":[297],"(GI)":[298],"AEs":[299,329,374,542],"predominantly":[300],"1/2":[303],"severity":[305],"were":[306,364,455,464,543],"most":[308],"common,":[309],"nausea":[313],"occurring":[315,321,349],"7":[317],"patients,":[318],"vomiting":[320],"6":[323],"patients.":[324,592],"majority":[326],"GI":[328],"improved":[330],"or":[331],"resolved":[332],"concomitant":[334],"medications.":[335],"Thrombocytopenia":[336],"3/4":[341],"AE":[342],"reported":[343],"more":[345],"than":[346,414],"patient,":[348],"(1":[353],"level).":[357],"Notably,":[358],"no":[359,387],"events":[360],"peripheral":[362],"neuropathy":[363],"noted":[365],"first":[370,443,585],"led":[375],"discontinuation":[377],"2":[379,605],"level,":[385],"deaths":[388],"reported.":[391],"showed":[393],"dose-dependent":[394],"exposure":[395,410,504],"across":[396,488,583],"120-":[398],"levels.":[402],"receiving":[404,416],"split":[405,449],"had":[407],"similar":[408,456],"total":[409,422],"lower":[412],"Cmax":[413],"QD":[417],"same":[421],"dose,":[424],"although":[425],"there":[426],"high":[428],"inter-patient":[429],"variability.":[430],"Dose-dependent":[431,564],"inhibition":[433,453,566,571],"observed":[435],"whole":[437],"blood":[438],"increased":[440],"from":[441],"second":[446],"doses.":[451],"Proteasome":[452],"levels":[454,588],"those":[458],"achieved":[459],"single-dose":[461],"equivalents":[462],">80%":[465,570],"level.":[470],"Eight":[471],"evaluable":[476],"efficacy.":[478],"There":[479],"preliminary":[481],"evidence":[482],"anti-tumor":[484],"activity":[485,582],"\u2265SD":[487],"chronic":[495],"lymphocytic":[496],"leukemia":[497],"attained":[499],"PR":[501,512],"after":[502],"lines":[507],"therapy,":[509],"MR":[515],"multiple":[519],"myeloma.":[520],"Conclusions:":[521],"Oral":[522],"generally":[525,544],"well":[526],"this":[533],"trial":[536],"mild":[545],"manageable.":[547],"An":[548],"has":[550],"not":[551,631],"reached":[553],"cumulative":[555],"doses":[556],"up":[557],"180":[559],"mg/d":[560],"BID).":[563],"observed,":[568],"highest":[574],"tested.":[576],"also":[578],"demonstrated":[579],"encouraging":[580],"clinical":[581,624],"heavily":[590],"pretreated":[591],"will":[595],"continue":[596],"reached,":[601],"planned":[603],"expansion":[606],"Disclosures:":[615],"Off":[616],"Label":[617],"Use:":[618],"Phase":[622],"trials":[625],"approved":[632],"FDA":[635],"any":[637],"use.":[638],"Lee:Onyx":[639,645],"Pharmaceuticals:":[640,643,646,649],"Employment.":[641,644,647,650],"Wong:Onyx":[642],"Gillenwater:Onyx":[648],"Siegel:Onyx:":[651],"Advisory":[652,654,662,664,671,678,680],"Board,":[653,663,679],"Board":[655,665,672,681],"Other,":[656,666,673,682],"Honoraria,":[657,667,674,683],"Speakers":[658,668,675,684],"Bureau;":[659,669,676],"Millennium":[660],"Pharma:":[661],"Celgene:":[670],"Merck:":[677],"Bureau.":[685]},"counts_by_year":[{"year":2015,"cited_by_count":1},{"year":2014,"cited_by_count":2},{"year":2013,"cited_by_count":6}],"updated_date":"2026-09-26T08:19:03.415552","created_date":"2016-11-30T00:00:00"}
