2024
Phase 1 trial safety and efficacy of ragistomig, a bispecific antibody targeting PD-L1 and 4-1BB, in advanced solid tumors.
Falchook G, LoRusso P, Goldman J, El-Khoueiry A, Tolcher A, Xing Y, Henry J, Keam B, Kim D, Kim T, Kim H, Hong M, Kim M, Lee D, Lee S, Jeon J, Hayslip J, Xu C, Garon E. Phase 1 trial safety and efficacy of ragistomig, a bispecific antibody targeting PD-L1 and 4-1BB, in advanced solid tumors. Journal Of Clinical Oncology 2024, 42: 2529-2529. DOI: 10.1200/jco.2024.42.16_suppl.2529.Peer-Reviewed Original ResearchTreatment related adverse eventsClinical benefit rateOverall response ratePD-L1Dose levelsPD-(L)1Complete responsePartial responseSolid tumorsHead and neck squamous cellAntibody targeting PD-L1Treated with checkpoint inhibitorsActivation of T cellsDose-limiting toxicityPre-treated patientsPD-(L)1 inhibitorsDose-expansion cohortRelapsed/refractory solid tumorsWeight-based dosingLines of treatmentPD-L1 antagonistsRelated adverse eventsAnti-tumor effectsDose-dependent increaseMultiple tumor typesA phase I study of ATR inhibitor BAY1895344 (elimusertib) plus topotecan (ETCTN 10402): Results of dose escalation.
Stockton S, Shyr C, Cecchini M, Aljumaily R, Halfdanarson T, Sonbol M, Whisenant J, Ivy S, LoRusso P, Das S, Gore S, Berlin J, Beumer J, Heumann T. A phase I study of ATR inhibitor BAY1895344 (elimusertib) plus topotecan (ETCTN 10402): Results of dose escalation. Journal Of Clinical Oncology 2024, 42: 3076-3076. DOI: 10.1200/jco.2024.42.16_suppl.3076.Peer-Reviewed Original ResearchMaximum tolerated doseDose escalationDose levelsMedian progression-free survivalRecommended phase 2 doseRefractory advanced solid tumorsResults of dose escalationTreatment-related adverse eventsSmall cell lung cancerDisease control ratePhase 2 dosePhase Ia studyDose-limiting toxicityProgression-free survivalAdvanced solid tumorsPhase I studyCell lung cancerAnti-tumor activityExpansion cohortPartial responseTolerated doseTopotecan exposureStudy drugCancer xenograftsRespiratory failure
2023
A phase 1a dose-escalation study of PY159, a monoclonal antibody targeting TREM1 (triggering receptor expressed on myeloid cells 1).
Winer I, Patnaik A, Barve M, Kummar S, Schenk E, LoRusso P, Yeku O, Fu S, Jahchan N, Myers M, Liang L, Deegan D, Jackson L, Li Y, Reyno L, Chamberlain M. A phase 1a dose-escalation study of PY159, a monoclonal antibody targeting TREM1 (triggering receptor expressed on myeloid cells 1). Journal Of Clinical Oncology 2023, 41: 2523-2523. DOI: 10.1200/jco.2023.41.16_suppl.2523.Peer-Reviewed Original ResearchSingle agentDose levelsNon-small cell lung cancerAdvanced refractory solid tumorsDose-escalation study designImmune-related adverse eventsTriple-negative breast cancerImmune checkpoint inhibitorsAcceptable safety profileDose-escalation studyRefractory solid tumorsCell lung cancerArchival tumor tissueEnrollment of subjectsImmune-related reactionsDose proportionalECOG PSRECIST 1.1Stable diseaseTREM1 expressionCheckpoint inhibitorsAdverse eventsPartial responseRadiographic responseGynecologic cancer
2022
NCI 9938: Phase I clinical trial of ATR inhibitor berzosertib (M6620, VX-970) in combination with irinotecan in patients with advanced solid tumors.
Villaruz L, Kelly K, Waqar S, Davis E, Shapiro G, LoRusso P, Dees E, Normolle D, Rhee J, Chu E, Gore S, Beumer J. NCI 9938: Phase I clinical trial of ATR inhibitor berzosertib (M6620, VX-970) in combination with irinotecan in patients with advanced solid tumors. Journal Of Clinical Oncology 2022, 40: 3012-3012. DOI: 10.1200/jco.2022.40.16_suppl.3012.Peer-Reviewed Original ResearchDose-limiting toxicityExperienced dose-limiting toxicityCell lung cancerColorectal cancerPancreatic cancerLung cancerDose levelsSolid tumorsNon-small cell lung cancerCommon treatment-related gradeGrade 3 lung infectionStage IISmall cell lung cancerPhase I clinical trialDose-expansion cohortsGrade 3 diarrheaMutant solid tumorsPhase II doseTreatment-related gradeGrade 2 diarrheaAdvanced solid tumorsManageable side effectsDose-escalation designMutant colorectal cancerEfficacy of irinotecanA first-in-human, phase 1 study of ASTX029, a dual-mechanism inhibitor of ERK1/2, in relapsed/refractory solid tumors.
LoRusso P, Rasco D, Shapiro G, Mita A, Azad N, Swiecicki P, El-Khoueiry A, Gandara D, Kummar S, Tanajian H, Taylor J, Bottone F, Toguchi M, Hindley C, Chan D, Oganesian A, Keer H, Dao K, Sullivan R, Spira A. A first-in-human, phase 1 study of ASTX029, a dual-mechanism inhibitor of ERK1/2, in relapsed/refractory solid tumors. Journal Of Clinical Oncology 2022, 40: 9085-9085. DOI: 10.1200/jco.2022.40.16_suppl.9085.Peer-Reviewed Original ResearchRefractory solid tumorsPhase 1 studyCentral serous retinopathyDose levelsSolid tumorsPartial responseOpen-label phase 1 studyPhase 1bNon-small cell lung cancerTarget exposurePD effectsDose-limiting toxicity eventsPhase 2 dosePhase 2 studyPreliminary clinical activityCell lung cancerDaily dose levelsDose-escalation designDays of dosingFresh tumor biopsiesClass of drugsPhase 1aExtracellular signal-regulated kinase 1/2 (ERK1/2) inhibitorNSCLC subjectsOcular AEs
2021
Phase 1 trial of a novel, first-in-class G protein-coupled estrogen receptor (GPER) agonist, LNS8801, in patients with advanced or recurrent treatment-refractory solid malignancies.
Muller C, Brown-Glaberman U, Chaney M, Garyantes T, LoRusso P, McQuade J, Mita A, Mita M, Natale C, Orloff M, Papadopoulos K, Sato T, Yilmaz E, Rodon J. Phase 1 trial of a novel, first-in-class G protein-coupled estrogen receptor (GPER) agonist, LNS8801, in patients with advanced or recurrent treatment-refractory solid malignancies. Journal Of Clinical Oncology 2021, 39: 3084-3084. DOI: 10.1200/jco.2021.39.15_suppl.3084.Peer-Reviewed Original ResearchG protein-coupled estrogen receptorC-Myc depletionStable diseaseDose levelsMetastatic solid tumor malignanciesAnti-PD-1 antibodyProtein-coupled estrogen receptorHr of dosingPhase 2 doseRECIST partial responseTreatment-related SAEsImmune checkpoint inhibitorsPhase 1 trialSolid tumor malignanciesPK/PD dataSelective small molecule agonistHigh unmet needDays of treatmentAnti-tumor activityEstrogen receptor agonistsSmall molecule agonistsTumor immune recognitionG protein-coupled receptorsAnti-cancer therapyCombination cohort
2020
412 First-in-human phase I/IIa trial to evaluate the safety and initial clinical activity of DuoBody®-PD-L1×4–1BB (GEN1046) in patients with advanced solid tumors
Garralda E, Geva R, Ben-Ami E, Maurice-Dror C, Calvo E, LoRusso P, Türeci Ö, Niewood M, Şahin U, Jure-Kunkel M, Forssmann U, Ahmadi T, Melero I. 412 First-in-human phase I/IIa trial to evaluate the safety and initial clinical activity of DuoBody®-PD-L1×4–1BB (GEN1046) in patients with advanced solid tumors. Journal For ImmunoTherapy Of Cancer 2020, 8: a250-a251. DOI: 10.1136/jitc-2020-sitc2020.0412.Peer-Reviewed Original ResearchAdvanced solid tumorsDose-limiting toxicityPhase I/IIa trialTransaminase elevationAdverse eventsSolid tumorsIIa trialClinical activityT cellsDose levelsGrade 3 transaminase elevationTreatment-related adverse eventsEffector memory T cellsSerum interferon-gamma levelTriple-negative breast cancerInitial clinical activityAntitumor activityImmune checkpoint inhibitorsManageable safety profilePD-L1 axisInterferon-gamma levelsMemory T cellsEarly clinical activityEnd of infusionNarrow therapeutic windowPharmacodynamic effects in blood and tumor tissue of eftozanermin alfa, a tumor necrosis factor-related apoptosis-inducing ligand receptor agonist.
Motwani M, Modi D, Penugonda S, Zhang C, Palma J, Cunningham A, Calvo E, de Jonge M, LoRusso P. Pharmacodynamic effects in blood and tumor tissue of eftozanermin alfa, a tumor necrosis factor-related apoptosis-inducing ligand receptor agonist. Journal Of Clinical Oncology 2020, 38: e15668-e15668. DOI: 10.1200/jco.2020.38.15_suppl.e15668.Peer-Reviewed Original ResearchPharmacodynamic effectsReceptor agonistMultiplex immunohistochemistryKRAS-mutant colorectal cancerTumor tissueDose-expansion cohortsSimilar time pointsMutant allele fractionM65 levelsH postdoseColorectal cancerPost-TxDownstream pathway activationPancreatic cancerHematologic malignanciesLiver enzymesScreening periodReverse phase protein arrayBiopsy coresTumor biopsiesMutant allele frequencyBiopsy samplesDose levelsBiopsyTumor types
2019
466P Interim results from trial of SL-801, a novel XPO-1 inhibitor, in patients with advanced solid tumours
Wang J, Barve M, Chiorean E, LoRusso P, Courtney K, Qi D, Bullington J, Sardone M, Chen J, Brooks C, Shemesh S, Bauer T. 466P Interim results from trial of SL-801, a novel XPO-1 inhibitor, in patients with advanced solid tumours. Annals Of Oncology 2019, 30: v175. DOI: 10.1093/annonc/mdz244.028.Peer-Reviewed Original ResearchSchedule ADay 1Optimal dose/schedulePreliminary anti-tumor activityDose-escalation stageStudy dose levelsMetastatic solid tumorsDose/scheduleAggressive tumor behaviorAnti-tumor activityAssess pharmacokineticsStarting doseDose intensityStandard therapyPoor prognosisHematologic malignanciesTumor behaviorDose levelsSolid tumorsPatientsNuclear export proteinVivo activityDoseLonger recovery timeDays457P First-in-human study of ABBV-621 in patients (pts) with previously treated sold tumours: Dose-optimization cohorts
Calvo E, de Jonge M, Rasco D, Moreno V, Chang Y, Chiney M, Motwani M, Penugonda S, Petrich A, Ratain M, LoRusso P. 457P First-in-human study of ABBV-621 in patients (pts) with previously treated sold tumours: Dose-optimization cohorts. Annals Of Oncology 2019, 30: v169-v170. DOI: 10.1093/annonc/mdz244.019.Peer-Reviewed Original ResearchDose levelsPancreatic cancerNon-cardiac chest painGenentech/RochePhase 2 dosePrior treatment regimensAntitumor activityAcceptable safety profileDose-limiting toxicityRoche/GenentechDeath receptor 4Bristol-Myers SquibbEligible ptsPleuritic painStable diseaseChest painGrade 3/4Respiratory failureMedian durationPartial responseToxic hepatitisDose escalationTreatment regimensSafety profileConclusion AdministrationPhase 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
Phase I study combining the aurora kinase A (AURKA) inhibitor alisertib (Ali) with mFOLFOX in gastrointestinal (GI) cancer.
Goff L, Azad N, Stein S, Whisenant J, Vaishampayan U, Hochster H, Connolly R, Weise A, LoRusso P, El-Rifai W, Berlin J. Phase I study combining the aurora kinase A (AURKA) inhibitor alisertib (Ali) with mFOLFOX in gastrointestinal (GI) cancer. Journal Of Clinical Oncology 2017, 35: 2593-2593. DOI: 10.1200/jco.2017.35.15_suppl.2593.Peer-Reviewed Original ResearchGI cancersStandard platinum-based therapyCorrelative biomarker studyDisease control rateMost frequent toxicitiesPreliminary clinical activityPlatinum-based therapyMajority of ptsEvaluable ptsStable diseaseEligible patientsFrequent toxicitiesHematologic toxicityPartial responseStandard therapyDose escalationInhibition of AURKAControl rateGastrointestinal cancerPreclinical dataClinical activityPlatinum agentsDose levelsInhibitor alisertibOptimal timing window
2013
A phase I, first-in-human study to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of IMGN853 in patients (Pts) with epithelial ovarian cancer (EOC) and other FOLR1-positive solid tumors.
Kurkjian C, LoRusso P, Sankhala K, Birrer M, Kirby M, Ladd S, Hawes S, Running K, O'Leary J, Moore K. A phase I, first-in-human study to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of IMGN853 in patients (Pts) with epithelial ovarian cancer (EOC) and other FOLR1-positive solid tumors. Journal Of Clinical Oncology 2013, 31: 2573-2573. DOI: 10.1200/jco.2013.31.15_suppl.2573.Peer-Reviewed Original ResearchNon-small cell lung cancerEpithelial ovarian cancerStudy drug-related serious adverse eventsAdverse eventsEndometrial cancerDose escalationDose levelsSolid tumorsAntibody-drug conjugatesRefractory non-small cell lung cancerDrug-related serious adverse eventsRefractory epithelial ovarian cancerResistant epithelial ovarian cancerClear cell renal cell cancerSerous epithelial ovarian cancerFLT-PET imagingPhase 2 doseSerious adverse eventsRefractory solid tumorsAccelerated titration designCell lung cancerRenal cell cancerPrimary study objectiveEvaluation of safetyGCIG criteria
2012
Safety, pharmacokinetics, and antitumor activity of MEDI-573, an investigational monoclonal antibody that targets IGF-I and IGF-II, in adult patients with advanced solid tumors.
Haluska P, Menefee M, Plimack E, Rosenberg J, Northfelt D, LaVallee T, Huang W, Yu X, Viner J, LoRusso P. Safety, pharmacokinetics, and antitumor activity of MEDI-573, an investigational monoclonal antibody that targets IGF-I and IGF-II, in adult patients with advanced solid tumors. Journal Of Clinical Oncology 2012, 30: tps2618-tps2618. DOI: 10.1200/jco.2012.30.15_suppl.tps2618.Peer-Reviewed Original ResearchMEDI-573Advanced solid tumorsSolid tumorsAdult patientsGlucose homeostasisDose levelsDrug-related adverse eventsMedian age 64 yearsAdequate organ functionIGF-I/-IIInvestigational monoclonal antibodyAntitumor activityAcceptable safety profileAdvanced bladder cancerAge 64 yearsKarnofsky statusQ3W dosingStable diseaseAdverse eventsSafety profileIGF-IIBladder cancerSerum glucoseSerious toxicityIGF-1R
2009
A first-in-human phase I study to evaluate the pan-PI3K inhibitor GDC-0941 administered QD or BID in patients with advanced solid tumors
Wagner A, Von Hoff D, LoRusso P, Tibes R, Mazina K, Ware J, Yan Y, Derynck M, Demetri G. A first-in-human phase I study to evaluate the pan-PI3K inhibitor GDC-0941 administered QD or BID in patients with advanced solid tumors. Journal Of Clinical Oncology 2009, 27: 3501-3501. DOI: 10.1200/jco.2009.27.15_suppl.3501.Peer-Reviewed Original ResearchDose-proportional increaseAnti-tumor activityDose levelsPK dataPan-PI3K inhibitor GDCSolid tumorsPhase ICA-125 responseDose escalation armDose-escalation cohortsDrug-related AEsGrade 1/2 nauseaPreliminary PK dataSingle-dose PKAdvanced solid tumorsTotal daily dosesFDG-PET uptakeSelective oral inhibitorSteady-state PKHuman phase IProstate cancer modelPotential signsBID armCancer ptsQD armPhase I study of MGCD265 administered intermittently to patients with advanced malignancies (Study 265–102)
Hong D, LoRusso P, Kurzrock R, Maroun C, Mehran M, Drouin M, Martell R, Wheler J. Phase I study of MGCD265 administered intermittently to patients with advanced malignancies (Study 265–102). Journal Of Clinical Oncology 2009, 27: e14516-e14516. DOI: 10.1200/jco.2009.27.15_suppl.e14516.Peer-Reviewed Original ResearchDose levelsSolid tumorsGrade 3 nonhematologic toxicityPhase IDrug-related AEsGrade 4 neutropeniaGrade 4 thrombocytopeniaAdvanced solid tumorsDrug-related toxicityTreatment of patientsDose-dependent increaseVariety of cancersEfficacious exposureNonhematologic toxicitySustained hypertensionAdvanced malignanciesEscalation studyFirst doseIntermittent administrationDisease progressionAvailable small moleculesPD markersXenograft modelPatientsDay 1
2007
A phase I study of EC145 administered weeks 1 and 3 of a 4-week cycle in patients with refractory solid tumors
Sausville E, LoRusso P, Quinn M, Forman K, Leamon C, Morganstern D, Bever S, Messmann R. A phase I study of EC145 administered weeks 1 and 3 of a 4-week cycle in patients with refractory solid tumors. Journal Of Clinical Oncology 2007, 25: 2577-2577. DOI: 10.1200/jco.2007.25.18_suppl.2577.Peer-Reviewed Original ResearchBolus dosesDay 1Folate receptorPhase IRefractory solid tumorsCommon side effectsFolic acidPhase I trialTime of presentationIntravenous bolus doseEligible patientsDisease stabilizationFlat doseI trialIntravenous bolusBolus doseMinor responsePK analysisSide effectsPatientsWeek 1Dose levelsEscalation plansSolid tumorsPK model
2006
Phase I pharmacokinetic (PK), and pharmacodynamic (PD) trial of the novel oral Notch inhibitor MK-0752 in patients (pts) with advanced breast cancer (BC) and other solid tumors
Krop I, Kosh M, Fearen I, Savoie J, Dallob A, Matthews C, Stone J, Winer E, Freedman S, Lorusso P. Phase I pharmacokinetic (PK), and pharmacodynamic (PD) trial of the novel oral Notch inhibitor MK-0752 in patients (pts) with advanced breast cancer (BC) and other solid tumors. Journal Of Clinical Oncology 2006, 24: 10574-10574. DOI: 10.1200/jco.2006.24.18_suppl.10574.Peer-Reviewed Original ResearchGrade 3 diarrheaAdvanced breast cancerBreast cancerPlasma AbetaDay 1Notch intracellular domainDose levelsSolid tumorsAccelerated dose escalationGamma-SecretaseGrade 2/3 fatigueMean PK parametersSubset of ptsElevated liver transaminasesAdvanced solid tumorsDaily oral dosingIntermittent dosing scheduleAnalysis of efficacyHuman breast cancerBC cell proliferationInhibition of NotchAbdominal crampingLiver transaminasesDosing schedulesPharmacodynamic trialA phase I dose escalation trial of ispinesib (SB-715992) administered days 1–3 of a 21-day cycle in patients with advanced solid tumors
Heath E, Alousi A, Eder J, Valdivieso M, Vasist L, Appleman L, Bhargava P, Colevas A, Lorusso P, Shapiro G. A phase I dose escalation trial of ispinesib (SB-715992) administered days 1–3 of a 21-day cycle in patients with advanced solid tumors. Journal Of Clinical Oncology 2006, 24: 2026-2026. DOI: 10.1200/jco.2006.24.18_suppl.2026.Peer-Reviewed Original ResearchGrade 4 neutropeniaAdvanced solid tumorsDose levelsDay 1Phosphohistone 3Solid tumorsGrade 3 febrile neutropeniaMultiple murine tumor modelsGrade 1 fatigueGrade 3 neutropeniaToxicity of myelosuppressionGrade 3/4 toxicitiesSerial tumor biopsiesRenal cell carcinomaMurine tumor modelsKinesin spindle proteinPreliminary pharmacokinetic dataSignificant antitumor activityNovel cytotoxic agentsEvaluable patientsFebrile neutropeniaMTD cohortStable diseaseEscalation trialCell carcinomaPhase-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