2024
Circulating Tumor DNA Dynamics Reveal KRAS G12C Mutation Heterogeneity and Response to Treatment with the KRAS G12C Inhibitor Divarasib in Solid Tumors
Choi Y, Dharia N, Jun T, Chang J, Royer-Joo S, Yau K, Assaf Z, Aimi J, Sivakumar S, Montesion M, Sacher A, LoRusso P, Desai J, Schutzman J, Shi Z, group A. Circulating Tumor DNA Dynamics Reveal KRAS G12C Mutation Heterogeneity and Response to Treatment with the KRAS G12C Inhibitor Divarasib in Solid Tumors. Clinical Cancer Research 2024, 30: of1-of10. PMID: 38995268, PMCID: PMC11369623, DOI: 10.1158/1078-0432.ccr-24-0255.Peer-Reviewed Original ResearchConceptsKRAS G12C mutationTumor fractionSolid tumorsTumor typesG12C mutationOn-treatment time pointsNon-small cell lung cancerMutational heterogeneityAssociated with tumor typeProgression-free survivalPlasma samplesPhase 1 studyCell lung cancerCycle 1 dayAssociated with patient outcomesVariant allele frequencyAssociated with responseCtDNA levelsCtDNA profilingMetastatic sitesTruncal mutationsTumor DNATreatment responseLung cancerTumor tissues
2021
Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19
Schmidt A, Tucker M, Bakouny Z, Labaki C, Hsu C, Shyr Y, Armstrong A, Beer T, Bijjula R, Bilen M, Connell C, Dawsey S, Faller B, Gao X, Gartrell B, Gill D, Gulati S, Halabi S, Hwang C, Joshi M, Khaki A, Menon H, Morris M, Puc M, Russell K, Shah D, Shah N, Sharifi N, Shaya J, Schweizer M, Steinharter J, Wulff-Burchfield E, Xu W, Zhu J, Mishra S, Grivas P, Rini B, Warner J, Zhang T, Choueiri T, Gupta S, McKay R, Desai A, Cohen A, Olszewski A, Bardia A, Daher A, Brown A, Yeh A, Hsiao A, Cheng A, Zhou A, Beeghly-Fadiel A, Morgans A, Jha A, Menendez A, Fazio A, Nizam A, Ramirez A, Kulkarni A, Verma A, Elshoury A, Rivera A, Walden A, Piper-Vallillo A, Cook A, Li A, Cantrell A, Cabal A, Nohria A, Angevine A, Gulati A, Giordano A, Kasi A, Ajmera A, Elkrief A, Kariapper A, Loaiza-Bonilla A, Jayaraj A, Thakkar A, Russ A, Bashir B, Halmos B, Logan B, Wood B, Slawik B, Dixon B, French B, Routy B, Mavromatis B, Hayes-Lattin B, Barrow McCollough B, Fleissner B, Stith B, Wicher C, Schwartz C, Thomson C, Solorzano C, Granada C, Brown C, Hennessy C, Stratton C, Castellano C, Ang C, Mandapakala C, Wang C, Jani C, Su C, Misdary C, Chapman C, McNair C, Lemmon C, Geiger C, Friese C, Su C, McKeown C, Hoppenot C, Low C, Pillainayagam C, Ferrario C, Rock C, Gonzalez Gomez C, Masson C, Mundt D, Addison D, Flora D, Stover D, Kwon D, Hausrath D, Bowles D, Reuben D, Shafer D, Bitterman D, O' Sullivan D, Mahadevan D, Sohal D, Whaley D, Slosky D, Chism D, Hershman D, Doroshow D, Ravindranathan D, Farmakiotis D, Bhutani D, Vinh D, Freeman D, Johnson D, Hatton E, Van Allen E, Griffiths E, Davis E, Nakasone E, Loggers E, Robilotti E, Levine E, Cabebe E, Hsu E, Powell E, Nemecek E, Lau E, Durbin E, Bernicker E, Small E, Cook E, Gillaspie E, Reid E, Papadopoulos E, Tadesse E, Wehbe F, Lyman G, Schwartz G, Nagaraj G, Boland G, Demetri G, Batist G, Gantt Jr. G, Kloecker G, Shaw G, Riely G, Borno H, Saker H, Dzimitrowicz H, Nelson H, Khan H, Shaikh H, Polimera H, Chen J, Stratton J, Acoba J, Patel J, Connors J, Mather J, Henderson J, Dill J, Girard J, Warner J, Graber J, Papenburg J, Altman J, Hawley J, Clement J, Park J, Campian J, Philip J, Deeken J, Riess J, Rosenberg J, Loree J, Senefeld J, Kharofa J, Garcia J, Palmer J, Lewis J, Guido J, Fu J, Wu J, Jiang J, Gainor J, Klamerus J, Steve Lo K, Patel K, de Cardenas K, Vega-Luna K, Goldsmith K, Hansen K, Huber K, Stockerl-Goldstein K, Jeffords K, Hoskins K, Reynolds K, Cerrone K, Cortez K, Enriquez K, Rosen L, Lashley L, Pomerantz L, Smith L, Feldman L, Fecher L, Zubiri L, Liu L, Schapira L, Tachiki L, Weissmann L, Rosenstein L, Wang L, Tomasini M, Abidi M, Khan M, Shah M, Rovito M, Gatti-Mays M, Escobedo M, Alexander M, Bonnen M, Fiala M, Lewis M, Dailey M, Reeves M, Sueyoshi M, Portes M, Salazar M, Mulcahy M, Pasquinelli M, Lustberg M, Fiebach M, Luders M, Galsky M, Weiss M, Clark M, Smits M, Accordino M, Markham M, Gurley M, Thompson M, Bar M, Wagner M, Joyner M, Glover M, Wotman M, Braccioforte M, Marcum M, Seletyn M, Huynh-Le M, Santos Dutra M, Streckfuss M, Akhtari M, Gatson N, Bahadur N, Knox N, Edwin N, Pennell N, Bouganim N, Hafez N, Venepalli N, Williams N, Balanchivadze N, Ohri N, Butt O, Panagiotou O, Serrano O, Bohachek P, Egan P, Shah P, Caimi P, LoRusso P, Weinstein P, Yu P, Lammers P, Nuzzo P, Bindal P, Peddi P, Grover P, Zaman Q, Sica R, Rosovsky R, Elias R, Zon R, Gandhi R, Belenkaya R, Rice R, Buerki R, Herbst R, Mesa R, Lynch R, Nguyen R, Monahan R, Jhawar S, Alimohamed S, Jabbour S, Del Prete S, Mahmood S, Goel S, Revankar S, Matar S, Saif S, Mushtaq S, Wall S, Croessman S, Kligerman S, McWeeney S, Goyal S, Choi S, Brouha S, Taylor S, Vinayak S, Gadgeel S, Blau S, Hallmeyer S, Reid S, Williamson S, Fry S, May S, Berg S, Duda S, Greenland S, Murdock S, Subbiah S, Shah S, Shah S, Van Loon S, Ayre S, Owenby S, Rose S, Ahmad S, Zhang S, Latif T, Bekaii-Saab T, Cronin T, Nonato T, Rhodes T, Carducci T, Halfdanarson T, Sun T, Wise-Draper T, Masters T, Topaloglu U, Koshkin V, Mico V, Karivedu V, Walters W, Miller Jr. W, Li X, Rho Y, Xie Z, Sachs Z. Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19. JAMA Network Open 2021, 4: e2134330. PMID: 34767021, PMCID: PMC8590166, DOI: 10.1001/jamanetworkopen.2021.34330.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAndrogen AntagonistsCohort StudiesCOVID-19HumansMaleMiddle AgedProstatic NeoplasmsRisk FactorsTennesseeConceptsAndrogen deprivation therapySARS-CoV-2 infectionProstate cancerPropensity matchingDeprivation therapyCohort studyMalignant neoplasmsEastern Cooperative Oncology Group performance status scoreRole of ADTCOVID-19Androgen deprivation therapy useLarge ongoing clinical trialsPharmacologic androgen deprivation therapyCOVID-19 infection severityAndrogen-targeted therapiesBaseline steroid usePerformance status scorePrimary end pointSecond malignant neoplasmsPrimary malignant neoplasmsMonths of presentationBody mass indexOngoing clinical trialsCOVID-19 treatmentVanderbilt University Medical Center
2020
Phase I Dose-Escalation and -Expansion Study of Telisotuzumab (ABT-700), an Anti–c-Met Antibody, in Patients with Advanced Solid Tumors
Strickler JH, LoRusso P, Salgia R, Kang YK, Yen C, Lin CC, Ansell P, Motwani M, Wong S, Yue H, Wang L, Reilly E, Afar D, Naumovski L, Ramanathan RK. Phase I Dose-Escalation and -Expansion Study of Telisotuzumab (ABT-700), an Anti–c-Met Antibody, in Patients with Advanced Solid Tumors. Molecular Cancer Therapeutics 2020, 19: 1210-1217. PMID: 32127466, DOI: 10.1158/1535-7163.mct-19-0529.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsSolid tumorsStable diseaseDose escalationCommon treatment-related adverse eventsAnti-c-Met antibodyTreatment-related adverse eventsDose-expansion phaseI Dose-EscalationAcceptable safety profileResponse Evaluation CriteriaDose-limiting toxicitySubset of patientsLinear pharmacokinetic profilePeak plasma concentrationAcute infusion reactionsHuman phase IDose cohortsDose expansionRECIST criteriaAdverse eventsEscalation cohortsInfusion reactionsObjective responsePartial responseDevelopment of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies
Falchook G, Rosen S, LoRusso P, Watts J, Gupta S, Coombs CC, Talpaz M, Kurzrock R, Mita M, Cassaday R, Harb W, Peguero J, Smith DC, Piha-Paul SA, Szmulewitz R, Noel MS, Yeleswaram S, Liu P, Switzky J, Zhou G, Zheng F, Mehta A. Development of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies. Clinical Cancer Research 2020, 26: 1247-1257. PMID: 31527168, PMCID: PMC7528620, DOI: 10.1158/1078-0432.ccr-18-4071.Peer-Reviewed Original ResearchConceptsAdvanced malignanciesGrade treatment-related adverse eventsTreatment-related adverse eventsAdequate organ functionHigh interpatient variabilityFavorable PK profileOptimal dosing schemePrimary endpointAdverse eventsOral clearancePartial responseComplete responsePhase 1/2Terminal eliminationTolerability studyPatient populationPharmacodynamic profileInterpatient variabilityDosing schemesDistinct pharmacokineticsTherapeutic indexOrgan functionPK profilesExtraterminal (BET) inhibitorsTarget inhibition
2019
Phase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced Solid Tumors
Jung KH, LoRusso P, Burris H, Gordon M, Bang YJ, Hellmann MD, Cervantes A, de Olza M, Marabelle A, Hodi FS, Ahn MJ, Emens LA, Barlesi F, Hamid O, Calvo E, McDermott D, Soliman H, Rhee I, Lin R, Pourmohamad T, Suchomel J, Tsuhako A, Morrissey K, Mahrus S, Morley R, Pirzkall A, Davis SL. Phase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced Solid Tumors. Clinical Cancer Research 2019, 25: 3220-3228. PMID: 30770348, PMCID: PMC7980952, DOI: 10.1158/1078-0432.ccr-18-2740.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorHumansImidazolesIndoleamine-Pyrrole 2,3,-DioxygenaseIndolesMagnetic Resonance ImagingMiddle AgedNeoplasm MetastasisNeoplasm StagingNeoplasmsTomography, X-Ray ComputedTreatment OutcomeConceptsPD-L1 inhibitorsT cellsPartial responseAdvanced cancerDay 1Dose levelsCommon treatment-related AEsDose-escalation stageTreatment-related AEsAdvanced solid tumorsEffector T cellsRegulatory T cellsLinear pharmacokinetic profileLocal tumor microenvironmentInvestigational small-molecule inhibitorExpansion patientsKynurenine accumulationComplete responseImmune suppressionIntravenous infusionAcceptable safetyTryptophan depletionNavoximodAtezolizumabPlasma Kyn
2017
A Phase I–II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors
Kristeleit R, Shapiro GI, Burris HA, Oza AM, LoRusso P, Patel MR, Domchek SM, Balmaña J, Drew Y, Chen LM, Safra T, Montes A, Giordano H, Maloney L, Goble S, Isaacson J, Xiao J, Borrow J, Rolfe L, Shapira-Frommer R. A Phase I–II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors. Clinical Cancer Research 2017, 23: 4095-4106. PMID: 28264872, DOI: 10.1158/1078-0432.ccr-16-2796.Peer-Reviewed Original ResearchConceptsHigh-grade ovarian carcinomaObjective response rateInvestigator-assessed objective response rateOral rucaparibAdverse eventsCommon treatment-emergent adverse eventsTreatment-emergent adverse eventsAspartate transaminase elevationsAsthenia/fatigueProtocol-defined criteriaRECIST version 1.1Phase II doseAdvanced solid tumorsProgression-free intervalSmall molecule PARP inhibitorsClin Cancer ResManageable toxicityPrior regimensPrimary endpointTransaminase elevationPlatinum therapyMultiple dosesOvarian carcinomaAlanine transaminaseClinical activity
2016
A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal or Reduced Hepatic Function
Li C, Agarwal P, Gibiansky E, Jin J, Dent S, Gonçalves A, Nijem I, Strasak A, Harle-Yge M, Chernyukhin N, LoRusso P, Girish S. A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal or Reduced Hepatic Function. Clinical Pharmacokinetics 2016, 56: 1069-1080. PMID: 27995530, DOI: 10.1007/s40262-016-0496-y.Peer-Reviewed Original ResearchConceptsNormal hepatic functionModerate hepatic impairmentHepatic impairmentMetastatic breast cancerHepatic functionTrastuzumab emtansineBreast cancerCycle 1Positive metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Phase I pharmacokinetic studyHuman epidermal growth factor receptorChild-Pugh criteriaMild hepatic impairmentT-DM1 3.6T-DM1 exposureGrowth factor receptor 2I pharmacokinetic studyFactor receptor 2Epidermal growth factor receptorGrowth factor receptorModerate cohortBaseline albuminT-DM1Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study
Nogova L, Sequist LV, Garcia J, Andre F, Delord JP, Hidalgo M, Schellens JH, Cassier PA, Camidge DR, Schuler M, Vaishampayan U, Burris H, Tian GG, Campone M, Wainberg ZA, Lim WT, LoRusso P, Shapiro GI, Parker K, Chen X, Choudhury S, Ringeisen F, Graus-Porta D, Porter D, Isaacs R, Buettner R, Wolf J. Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study. Journal Of Clinical Oncology 2016, 35: 157-165. PMID: 27870574, PMCID: PMC6865065, DOI: 10.1200/jco.2016.67.2048.Peer-Reviewed Original ResearchConceptsFibroblast growth factor receptorGrowth factor receptorUrothelial cancerSafety profileAntitumor activitySolid tumorsGenetic alterationsKinase inhibitorsDose-expansion studyFGFR genetic alterationsMethods Adult patientsMTD/RP2DCommon adverse eventsManageable safety profilePhase II doseSimilar safety profileAdvanced solid tumorsContinuous scheduleDose-limiting toxicityFactor receptorCell lung cancerGrowth factor receptor 1Tyrosine kinase inhibitorsFibroblast growth factor receptor 1Factor receptor 1
2011
Dose-escalating and pharmacological study of bortezomib in adult cancer patients with impaired renal function: a National Cancer Institute Organ Dysfunction Working Group Study
Leal T, Remick S, Takimoto C, Ramanathan R, Davies A, Egorin M, Hamilton A, LoRusso P, Shibata S, Lenz H, Mier J, Sarantopoulos J, Mani S, Wright J, Ivy S, Neuwirth R, von Moltke L, Venkatakrishnan K, Mulkerin D. Dose-escalating and pharmacological study of bortezomib in adult cancer patients with impaired renal function: a National Cancer Institute Organ Dysfunction Working Group Study. Cancer Chemotherapy And Pharmacology 2011, 68: 1439-1447. PMID: 21479634, PMCID: PMC3481841, DOI: 10.1007/s00280-011-1637-5.Peer-Reviewed Original ResearchConceptsSevere renal dysfunctionNormal renal functionRenal dysfunctionAdult cancer patientsRenal functionDialysis patientsDose escalationCancer patientsPatient populationNational Cancer Institute Organ Dysfunction Working Group StudyDose of bortezomibImpaired renal functionGeneral patient populationIntravenous bortezomibRenal impairmentCreatinine clearanceModerate dysfunctionMild dysfunctionSevere dysfunctionDose reductionPharmacologic dataPatientsDay 1DysfunctionBortezomib
2009
Phase I Dose-Escalation and Pharmacokinetic Study of Dasatinib in Patients with Advanced Solid Tumors
Demetri G, Russo P, MacPherson I, Wang D, Morgan J, Brunton V, Paliwal P, Agrawal S, Voi M, Evans T. Phase I Dose-Escalation and Pharmacokinetic Study of Dasatinib in Patients with Advanced Solid Tumors. Clinical Cancer Research 2009, 15: 6232-6240. PMID: 19789325, DOI: 10.1158/1078-0432.ccr-09-0224.Peer-Reviewed Original ResearchConceptsDose-limiting toxicitySolid tumorsHematologic toxicityFrequent treatment-related toxicitiesDurable stable diseaseGrade 2 proteinuriaGrade 2 rashGrade 3 fatigueGrade 3 hypocalcemiaGrade 3 lethargyGrade 3 nauseaI Dose-EscalationLess hematologic toxicityGrade 3 rashObjective tumor responsePhase II doseTreatment-related toxicityAdvanced solid tumorsDose-escalation studyMetastatic solid tumorsStandard therapy existsNontreatment daysStable diseaseDaily dosingStandard therapy
2008
Phase I and Pharmacokinetic Study of Imatinib Mesylate in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction: A Study by the National Cancer Institute Organ Dysfunction Working Group
Ramanathan R, Egorin M, Takimoto C, Remick S, Doroshow J, LoRusso P, Mulkerin D, Grem J, Hamilton A, Murgo A, Potter D, Belani C, Hayes M, Peng B, Ivy S. Phase I and Pharmacokinetic Study of Imatinib Mesylate in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction: A Study by the National Cancer Institute Organ Dysfunction Working Group. Journal Of Clinical Oncology 2008, 26: 563-569. PMID: 18235115, DOI: 10.1200/jco.2007.11.0304.Peer-Reviewed Original ResearchConceptsNausea/vomitingLiver dysfunctionLiver functionLD groupNational Cancer Institute Organ Dysfunction Working GroupLiver function test elevationsPlasma concentration-time curveD dose levelDose of imatinibDoses of imatinibSevere liver dysfunctionDose-limiting toxicityMild liver dysfunctionSerum total bilirubinNormal liver functionPharmacokinetics of imatinibDose-normalized areaConcentration-time curveConcentrations of imatinibImatinib doseAdvanced malignanciesImatinib exposureMaximal doseImatinib mesylateRenal excretion
2001
Chronic Oral Administration of CI-994: A Phase I Study
Prakash S, Foster B, Meyer M, Wozniak A, Heilbrun L, Flaherty L, Zalupski M, Radulovic L, Valdivieso M, LoRusso P. Chronic Oral Administration of CI-994: A Phase I Study. Investigational New Drugs 2001, 19: 1-11. PMID: 11291827, DOI: 10.1023/a:1006489328324.Peer-Reviewed Original ResearchConceptsHuman tumor xenograftsCI-994Dosing phaseStable diseaseTumor xenograftsNon-small cell lungNovel oral agentsChronic oral administrationDaily oral dosePeak plasma levelsRat leukemia modelOral agentsStarting doseDosage escalationGastrointestinal effectsDaily administrationOral doseCell lungPlasma levelsSingle dosesOral administrationRenal cancerChronic basisFood intakeTreatment duration
1998
Evaluation of pyrazoloacridine in patients with advanced pancreatic carcinoma
Zalupski M, Shields A, Philip P, Kraut M, LoRusso P, Heilbrun L, Vaitkevicius V. Evaluation of pyrazoloacridine in patients with advanced pancreatic carcinoma. Investigational New Drugs 1998, 16: 93-96. PMID: 9740550, DOI: 10.1023/a:1006087114621.Peer-Reviewed Original ResearchConceptsPancreatic carcinomaBroad preclinical antitumor activityUntreated advanced pancreatic cancerAdvanced pancreatic cancerAdvanced pancreatic carcinomaPhase II trialSchedule of administrationPreclinical antitumor activityModerate neutropeniaPredictable toxicityII trialMajor toxicityClinical efficacyMild neurotoxicityPancreatic cancerClinical developmentPatientsPyrazoloacridinePhase IAntitumor activitySolid tumor selectivityTumor selectivityCarcinomaDoseToxicity
1997
Phase II study of pyrazoloacridine in patients with advanced colorectal carcinoma
Zalupski M, Philip P, LoRusso P, Shields A. Phase II study of pyrazoloacridine in patients with advanced colorectal carcinoma. Cancer Chemotherapy And Pharmacology 1997, 40: 225-227. PMID: 9219505, DOI: 10.1007/s002800050650.Peer-Reviewed Original ResearchConceptsColorectal cancerBroad preclinical antitumor activityUntreated advanced colorectal cancerPhase II studyAdvanced colorectal cancerPhase II trialSchedule of administrationAdvanced colorectal carcinomaPreclinical antitumor activityPredictable toxicityII trialII studyClinical efficacyColorectal carcinomaClinical developmentPatientsPyrazoloacridinePhase IAntitumor activitySolid tumor selectivityTumor selectivityCancerDoseToxicityMyelosuppression