2023
A First-in-Human Phase I Study of Milademetan, an MDM2 Inhibitor, in Patients With Advanced Liposarcoma, Solid Tumors, or Lymphomas
Gounder M, Bauer T, Schwartz G, Weise A, LoRusso P, Kumar P, Tao B, Hong Y, Patel P, Lu Y, Lesegretain A, Tirunagaru V, Xu F, Doebele R, Hong D. A First-in-Human Phase I Study of Milademetan, an MDM2 Inhibitor, in Patients With Advanced Liposarcoma, Solid Tumors, or Lymphomas. Journal Of Clinical Oncology 2023, 41: 1714-1724. PMID: 36669146, PMCID: PMC10022862, DOI: 10.1200/jco.22.01285.Peer-Reviewed Original ResearchConceptsMedian progression-free survivalDisease control rateProgression-free survivalControl rateDedifferentiated liposarcomaGrade 3/4 drug-related adverse eventsMurine double minute 2 inhibitorsSolid tumorsIntermittent scheduleDrug-related adverse eventsHuman Phase I StudyRandomized phase III trialPhase II doseAdvanced solid tumorsPhase III trialsIntermittent dosing scheduleSingle-agent activityPhase I studiesHuman phase IAdvanced liposarcomaAdverse eventsIII trialsDosing schedulesAdvanced cancerEfficacy analysis
2022
A Phase 1 First-in-Human Study of FS118, a Tetravalent Bispecific Antibody Targeting LAG-3 and PD-L1 in Patients with Advanced Cancer and PD-L1 Resistance.
Yap T, LoRusso P, Wong D, Hu-Lieskovan S, Papadopoulos K, Holz J, Grabowska U, Gradinaru C, Leung K, Marshall S, Reader C, Russell R, Sainson R, Seal C, Shepherd C, Germaschewski F, Gliddon D, Stern O, Young L, Brewis N, Kayitalire L, Morrow M. A Phase 1 First-in-Human Study of FS118, a Tetravalent Bispecific Antibody Targeting LAG-3 and PD-L1 in Patients with Advanced Cancer and PD-L1 Resistance. Clinical Cancer Research 2022, 29: 888-898. PMID: 36342102, DOI: 10.1158/1078-0432.ccr-22-1449.Peer-Reviewed Original ResearchConceptsDisease control rateLAG-3PD-L1Advanced cancerOverall disease control rateDisease controlPeripheral effector cellsPhase 2 doseSerious adverse eventsPhase 1 studySoluble LAG-3Tetravalent bispecific antibodyPrior regimensStable diseaseDose expansionMetastatic settingAdverse eventsPartial responseEffector cellsClinical benefitControl rateSustained elevationTitration designPharmacodynamic activityHuman studies
2020
395 A first-in-human study of FS118, a tetravalent bispecific antibody targeting LAG-3 and PD-L1, in patients with advanced cancer and resistance to PD-(L)1 therapy
Yap T, Wong D, Hu-Lieskovan S, Papadopoulos K, Morrow M, Grabowska U, Gliddon D, Holz J, LoRusso P. 395 A first-in-human study of FS118, a tetravalent bispecific antibody targeting LAG-3 and PD-L1, in patients with advanced cancer and resistance to PD-(L)1 therapy. 2020, a240-a240. DOI: 10.1136/jitc-2020-sitc2020.0395.Peer-Reviewed Original ResearchPhase I/II dose-escalation and expansion study of FLX475 alone and in combination with pembrolizumab in advanced cancer.
Powderly J, Chmielowski B, Brahmer J, Piha-Paul S, Bowyer S, LoRusso P, Catenacci D, Wu C, Barve M, Chisamore M, Nasrah N, Johnson D, Ho W. Phase I/II dose-escalation and expansion study of FLX475 alone and in combination with pembrolizumab in advanced cancer. Journal Of Clinical Oncology 2020, 38: tps3163-tps3163. DOI: 10.1200/jco.2020.38.15_suppl.tps3163.Peer-Reviewed Original ResearchCheckpoint inhibitorsExpansion cohortT cellsPhase 1 dose escalationAnti-tumor immune responseTumor microenvironmentPhase I/IIPreliminary anti-tumor activityCohort expansion phaseCohort expansion studyPhase 2 dosePredominant chemokine receptorPhase 1/2 studyDose-escalation phaseEffector T cellsRegulatory T cellsAnti-tumor responseTumor-associated macrophagesAnti-tumor efficacyAnti-tumor activityEligible subjectsDendritic cellsDose escalationPhase 1/2Advanced cancerCX-2009, a CD166-directed probody drug conjugate (PDC): Results from the first-in-human study in patients (Pts) with advanced cancer including breast cancer (BC).
Boni V, Burris III H, Liu J, Spira A, Arkenau H, Fidler M, Rosen L, Sweis R, Uboha N, Sanborn R, O'Neil B, Harding J, LoRusso P, Weise A, Garcia-Corbacho J, Victoria I, Frye J, Li R, Stroh M, Meric-Bernstam F. CX-2009, a CD166-directed probody drug conjugate (PDC): Results from the first-in-human study in patients (Pts) with advanced cancer including breast cancer (BC). Journal Of Clinical Oncology 2020, 38: 526-526. DOI: 10.1200/jco.2020.38.15_suppl.526.Peer-Reviewed Original ResearchTreatment-related adverse eventsBreast cancerQ3w scheduleAdvanced cancerGrade 3 treatment-related adverse eventsHuman studiesCommon treatment-related adverse eventsMultiple solid tumor modelsInfusion-related reactionsPhase II doseAdvanced solid tumorsDose-escalation phaseDose-escalation studyPhase II expansionClinical trial informationPopulation pharmacokinetic simulationsMicrotubule inhibitorsSolid tumor modelsTumor-associated proteasesCX-072Prior therapyQ2W dosingQ3W dosingAdverse eventsPartial response
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 KynA phase I/Ib multicenter study to evaluate the humanized anti-CD73 antibody, CPI-006, as a single agent, in combination with CPI-444, and in combination with pembrolizumab in adult patients with advanced cancers.
Mobasher M, Miller R, Kwei L, Strahs D, Das V, Luciano G, Powderly J, Merchan J, Barve M, LoRusso P, Tripathi A, Luke J. A phase I/Ib multicenter study to evaluate the humanized anti-CD73 antibody, CPI-006, as a single agent, in combination with CPI-444, and in combination with pembrolizumab in adult patients with advanced cancers. Journal Of Clinical Oncology 2019, 37: tps2646-tps2646. DOI: 10.1200/jco.2019.37.15_suppl.tps2646.Peer-Reviewed Original ResearchSingle agentCD73 antibodyTumor growthNon-small cell lungAdequate organ functionAnti-CD73 antibodiesOpen-label trialTreatment of patientsRenal cell carcinomaSelective A2AR antagonistNumber of malignanciesKnockout mice exhibitTriple-negative breastEligible patientsMeasurable diseaseLabel trialAdult patientsStandard therapyAdvanced cancerCD73 expressionImmunosuppressive adenosineMulticenter studyUrothelial bladderCell carcinomaCell lung
2018
ICONIC: Biologic and clinical activity of first in class ICOS agonist antibody JTX-2011 +/- nivolumab (nivo) in patients (pts) with advanced cancers.
Yap T, Burris H, Kummar S, Falchook G, Pachynski R, LoRusso P, Tykodi S, Gibney G, Gainor J, Rahma O, Seiwert T, Meric-Bernstam F, Blum Murphy M, Litton J, Hooper E, Hirsch H, Harvey C, Clancy M, McClure T, Callahan M. ICONIC: Biologic and clinical activity of first in class ICOS agonist antibody JTX-2011 +/- nivolumab (nivo) in patients (pts) with advanced cancers. Journal Of Clinical Oncology 2018, 36: 3000-3000. DOI: 10.1200/jco.2018.36.15_suppl.3000.Peer-Reviewed Original Research
2014
Erratum to: Phase I study of PF-04691502, a small-molecule, oral, dual inhibitor of PI3K and mTOR, in patients with advanced cancer
Britten C, Adjei A, Millham R, Houk B, Borzillo G, Pierce K, Wainberg Z, LoRusso P. Erratum to: Phase I study of PF-04691502, a small-molecule, oral, dual inhibitor of PI3K and mTOR, in patients with advanced cancer. Investigational New Drugs 2014, 32: 575-575. DOI: 10.1007/s10637-014-0069-6.Peer-Reviewed Original Research
2013
Phase I study of REGN421 (R)/SAR153192, a fully-human delta-like ligand 4 (Dll4) monoclonal antibody (mAb), in patients with advanced solid tumors.
Jimeno A, LoRusso P, Strother R, Diamond J, Plato L, Younger A, Messersmith W, Kittaneh M, Sawyer D, Adriaens L, Liu L, Kao R, DiCioccio A, Brownstein C, Lowy I, Trail P, Chiorean E. Phase I study of REGN421 (R)/SAR153192, a fully-human delta-like ligand 4 (Dll4) monoclonal antibody (mAb), in patients with advanced solid tumors. Journal Of Clinical Oncology 2013, 31: 2502-2502. DOI: 10.1200/jco.2013.31.15_suppl.2502.Peer-Reviewed Original ResearchAbdominal painVentricular dysfunctionSolid tumorsGrade 3 nauseaGrade 3/4 AEsPhase II doseRight ventricular dysfunctionAcceptable safety profileAdvanced solid tumorsDose-escalation trialAnti-tumor activityBNP increaseCA125 responseHuman Dll4Prolonged SDsEscalation trialExpansion cohortPulmonary hypertensionLaboratory abnormalitiesDose escalationAdvanced cancerSafety profileFrequent treatmentHypertensionNausea
2012
497P Dose-Escalation Phase I Study of Cabazitaxel (CBZ) + Gemcitabine (GEM) in Patients (PTS) with Metastatic or Unresectable Advanced Solid Malignancy
Rixe O, Puzanov I, LoRusso P, Yin J, Doroumian S, Zhi X, Olszanski A. 497P Dose-Escalation Phase I Study of Cabazitaxel (CBZ) + Gemcitabine (GEM) in Patients (PTS) with Metastatic or Unresectable Advanced Solid Malignancy. Annals Of Oncology 2012, 23: ix170. DOI: 10.1016/s0923-7534(20)33059-3.Peer-Reviewed Original ResearchTreatment-emergent AEsAdministration sequenceFebrile neutropeniaMetastatic castration-resistant prostate cancerDose-escalation phase IAntitumour activityCastration-resistant prostate cancerPhase IPreliminary PK dataAdvanced solid malignanciesGrade 4 neutropeniaAlternative dosing regimensDrug-drug interactionsUnresectable solid tumorsDrug administration sequenceStable diseaseHaematological toxicityTaxane combinationsOverall survivalPartial responseAdvanced cancerDosing regimensGEM 1000Study treatmentTolerable combination
2011
Phase I study of TAK-285, an investigational HER2/EGFR inhibitor, in patients (pts) with advanced cancer: Updated results and assessment of human CSF distribution.
Chiorean E, Sausville E, Heath E, Weise A, Gomez-Navarro J, Venkatakrishnan K, Sankoh S, Wu J, Corvez M, LoRusso P. Phase I study of TAK-285, an investigational HER2/EGFR inhibitor, in patients (pts) with advanced cancer: Updated results and assessment of human CSF distribution. Journal Of Clinical Oncology 2011, 29: 2538-2538. DOI: 10.1200/jco.2011.29.15_suppl.2538.Peer-Reviewed Original Research
2010
364 The first-in-human, first-in-class study of CUDC-101, a multi-targeted inhibitor of HDAC, EGFR, and HER2: A Phase I study in patients with advanced cancer
Shimizu T, Tolcher A, LoRusso P, Papadopoulos K, Patnaik A, Smith L, Keegan M. 364 The first-in-human, first-in-class study of CUDC-101, a multi-targeted inhibitor of HDAC, EGFR, and HER2: A Phase I study in patients with advanced cancer. European Journal Of Cancer Supplements 2010, 8: 115. DOI: 10.1016/s1359-6349(10)72071-1.Peer-Reviewed Original Research383 First-in-human study of PF-04691502, a small molecule oral dual inhibitor of PI3K and mTOR in patients with advanced cancer: Preliminary report on safety and pharmacokinetics
Britten C, Adjei A, Millham R, Houk B, Wainberg Z, Guthrie T, Dy G, LoRusso P. 383 First-in-human study of PF-04691502, a small molecule oral dual inhibitor of PI3K and mTOR in patients with advanced cancer: Preliminary report on safety and pharmacokinetics. European Journal Of Cancer Supplements 2010, 8: 121-122. DOI: 10.1016/s1359-6349(10)72090-5.Peer-Reviewed Original Research
2007
A phase I dose escalation trial of a daily oral CDK 4/6 inhibitor PD-0332991
O’Dwyer P, LoRusso P, DeMichele A, Gupta V, Barbi A, Dials H, Chen I, Courtney R, Wilner K, Schwartz G. A phase I dose escalation trial of a daily oral CDK 4/6 inhibitor PD-0332991. Journal Of Clinical Oncology 2007, 25: 3550-3550. DOI: 10.1200/jco.2007.25.18_suppl.3550.Peer-Reviewed Original ResearchMTD/RP2DSchedule 2/1Stable diseasePD-0332991Escalation trialPhase IPositive solid tumorsRb-positive tumorsCommon tumor typesDose-dependent increaseNovel oral inhibitorEffect of foodPhospho-Rb proteinsCommon AEsPharmacodynamic modulationMedian ageAdvanced cancerOral inhibitorPositive tumorsTumor specimensPatientsSingle agentSolid tumorsTumor typesSuccessive dose
2006
648 POSTER A phase I dose-escalation study of weekly IMC-A12, a fully human insulin like growth factor-I receptor (IGF-IR) IgG1 monoclonal antibody (Mab), in patients (pts) with advanced cancer
Higano C, Gordon M, LoRusso P, Fox F, Katz T, Roecker J, Rowinsky E, Youssoufian H. 648 POSTER A phase I dose-escalation study of weekly IMC-A12, a fully human insulin like growth factor-I receptor (IGF-IR) IgG1 monoclonal antibody (Mab), in patients (pts) with advanced cancer. European Journal Of Cancer Supplements 2006, 4: 195. DOI: 10.1016/s1359-6349(06)70653-x.Peer-Reviewed Original ResearchPhase-1 study of isophosphoramide mustard (IPM)-lysine in advanced cancers
Gale R, Van Vugt A, Rosen L, Chang L, Lorusso P, Valdivieso M, Malburg L, Struck R, Morgan L. Phase-1 study of isophosphoramide mustard (IPM)-lysine in advanced cancers. Journal Of Clinical Oncology 2006, 24: 9524-9524. DOI: 10.1200/jco.2006.24.18_suppl.9524.Peer-Reviewed Original ResearchCNS toxicityAdvanced cancerProximal renal tubular acidosisExtensive prior therapyHuman-mouse xenograftsPhase 1 studyPhase 1 trialRenal tubular acidosisPre-clinical modelsDiverse cancer modelsGI complaintsPrior therapyStable diseaseCancer cell linesLimited diseaseStarting doseHemorrhagic cystitisMedian ageColorectal cancerTubular acidosisThyroid cancerDose levelsCancer modelGreater efficacyHuman cancer cell lines
2005
A phase 1–2 clinical study of a second generation oral MEK inhibitor, PD 0325901 in patients with advanced cancer
Lorusso P, Krishnamurthi S, Rinehart J, Nabell L, Croghan G, Varterasian M, Sadis S, Menon S, Leopold J, Meyer M. A phase 1–2 clinical study of a second generation oral MEK inhibitor, PD 0325901 in patients with advanced cancer. Journal Of Clinical Oncology 2005, 23: 3011-3011. DOI: 10.1200/jco.2005.23.16_suppl.3011.Peer-Reviewed Original Research
2004
Phase I dose-escalation trial investigating the safety and tolerability of EPO906 plus gemcitabine in patients with advanced cancer
Rinehart J, Rothermel J, Anderson J, Lorusso P. Phase I dose-escalation trial investigating the safety and tolerability of EPO906 plus gemcitabine in patients with advanced cancer. Journal Of Clinical Oncology 2004, 22: 3100-3100. DOI: 10.1200/jco.2004.22.14_suppl.3100.Peer-Reviewed Original ResearchPhase I dose-escalation trial investigating the safety and tolerability of EPO906 plus gemcitabine in patients with advanced cancer
Rinehart J, Rothermel J, Anderson J, Lorusso P. Phase I dose-escalation trial investigating the safety and tolerability of EPO906 plus gemcitabine in patients with advanced cancer. Journal Of Clinical Oncology 2004, 22: 3100-3100. DOI: 10.1200/jco.2004.22.90140.3100.Peer-Reviewed Original Research