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
2021
1033TiP A first-in-human phase I study of FS120, an OX40/CD137 tetravalent bispecific antibody, in patients with advanced malignancies
Papadopoulos K, Yap T, Piha-Paul S, Lorusso P, Hu-Lieskovan S, Shepherd C, Marshall S, Holz J, Poon E, Grabowska U, Kayitalire L. 1033TiP A first-in-human phase I study of FS120, an OX40/CD137 tetravalent bispecific antibody, in patients with advanced malignancies. Annals Of Oncology 2021, 32: s864-s865. DOI: 10.1016/j.annonc.2021.08.1417.Peer-Reviewed Original Research
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 responseA First-in-Human Phase I Study to Evaluate the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors
Varga A, Soria JC, Hollebecque A, LoRusso P, Bendell J, Huang SA, Wagle MC, Okrah K, Liu L, Murray E, Sanabria-Bohorquez SM, Tagen M, Dokainish H, Mueller L, Burris H. A First-in-Human Phase I Study to Evaluate the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors. Clinical Cancer Research 2020, 26: 1229-1236. PMID: 31848189, DOI: 10.1158/1078-0432.ccr-19-2574.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedDose-Response Relationship, DrugFatigueFemaleHumansMaleMAP Kinase Signaling SystemMaximum Tolerated DoseMiddle AgedMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3NauseaNeoplasmsPatient SafetyProtein Kinase InhibitorsPyridonesPyrimidinesTissue DistributionVomitingConceptsBRAF-mutant colorectal cancerColorectal cancerAdverse eventsFDG-PETCommon drug-related adverse eventsSolid tumorsDrug-related adverse eventsPhase IPartial metabolic responseAcceptable safety profileAdvanced solid tumorsDose-proportional increaseGrade 3 rashMetastatic solid tumorsSerial tumor biopsiesSingle-agent activityBest overall responseHuman phase IMAPK pathway inhibitionMultiple tumor typesStable diseaseEscalation studyPartial responseOral inhibitorPharmacodynamic effects
2019
A first-in-human phase I study of FS118, an anti-LAG-3/PD-L1 bispecific antibody in patients with solid tumors that have progressed on prior PD-1/PD-L1 therapy.
Yap T, Papadopoulos K, LoRusso P, Wong D, Hu-Lieskovan S, Holz J. A first-in-human phase I study of FS118, an anti-LAG-3/PD-L1 bispecific antibody in patients with solid tumors that have progressed on prior PD-1/PD-L1 therapy. Journal Of Clinical Oncology 2019, 37: tps2652-tps2652. DOI: 10.1200/jco.2019.37.15_suppl.tps2652.Peer-Reviewed Original ResearchSafety Review CommitteePD-L1Dose escalationLAG-3PD-1/PD-L1 checkpoint inhibitorsPD-1/PD-L1 therapyPD-1/PD-L1 treatmentTranslational studiesSolid tumorsPD-1/PD-L1Immunotherapy-related adverse effectsPD-L1 checkpoint inhibitorsBispecific antibodiesLymphocyte activation gene-3PD-1 mAbPD-L1 treatmentPhase 2 dosePD-L1 therapyLAG-3 expressionMinority of patientsAnti-tumor responseSuperior anti-tumor efficacyEarly clinical trialsRemarkable anti-tumor activityHuman phase I
2016
18 A first-in-human phase I study to evaluate the ERK1/2 inhibitor GDC-0994 in patients with advanced solid tumors
Varga A, Soria J, Hollebecque A, LoRusso P, Vaishampayan U, Okrah K, Huang S, Murray E, Sanabria-Bohorquez S, Tagen M, Dokainish H, Mueller L, Burris H. 18 A first-in-human phase I study to evaluate the ERK1/2 inhibitor GDC-0994 in patients with advanced solid tumors. European Journal Of Cancer 2016, 69: s11. DOI: 10.1016/s0959-8049(16)32624-7.Peer-Reviewed Original Research
2014
2 Safety and early evidence of activity of a first-in-human phase I study of the novel cancer stem cell (CSC) targeting antibody OMP-52M51 (anti-Notch1) administered intravenously to patients with certain advanced solid tumors
Patnaik A, LoRusso P, Munster P, Tolcher A, Davis S, Heymach J, Ferraroto R, Xu L, Kapoun A, Faoro L, Lewicki J, Dupont J, Eckhardt S. 2 Safety and early evidence of activity of a first-in-human phase I study of the novel cancer stem cell (CSC) targeting antibody OMP-52M51 (anti-Notch1) administered intravenously to patients with certain advanced solid tumors. European Journal Of Cancer 2014, 50: 7. DOI: 10.1016/s0959-8049(14)70128-5.Peer-Reviewed Original Research
2012
A phase I study of MM-302, a HER2-targeted liposomal doxorubicin, in patients with advanced, HER2-positive (HER2+) breast cancer.
Munster P, Miller K, Krop I, Dhindsa N, Reynolds J, Geretti E, Niyikiza C, Nielsen U, Hendriks B, Wickham T, Moyo V, LoRusso P. A phase I study of MM-302, a HER2-targeted liposomal doxorubicin, in patients with advanced, HER2-positive (HER2+) breast cancer. Journal Of Clinical Oncology 2012, 30: tps663-tps663. DOI: 10.1200/jco.2012.30.15_suppl.tps663.Peer-Reviewed Original ResearchAdvanced breast cancerMaximum feasible doseBreast cancerMM-302Liposomal doxorubicinHER2-positive breast cancerTumor cellsAdequate performance statusAnthracycline-free regimensBone marrow reserveDose-escalation portionClinical benefit rateDose-limiting toxicityDose-escalation designHER2-positive cancersPreliminary efficacy dataHuman phase IStandard therapy existsBreast cancer therapyAvailable anthracyclinesPrimary endpointSecondary endpointsMarrow reservePerformance statusStandard therapy
2011
A first-in-human phase I study of U3-1287 (AMG 888), a HER3 inhibitor, in patients (pts) with advanced solid tumors.
Berlin J, Keedy V, Janne P, Yee L, Rizvi N, Jin X, Copigneaux C, Hettmann T, Beaupre D, LoRusso P. A first-in-human phase I study of U3-1287 (AMG 888), a HER3 inhibitor, in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2011, 29: 3026-3026. DOI: 10.1200/jco.2011.29.15_suppl.3026.Peer-Reviewed Original Research
2010
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.
Von Hoff D, LoRusso P, Tibes R, Shapiro G, Weiss G, Ware J, Fredrickson J, Mazina K, Levy G, Wagner A. 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 2010, 28: 2541-2541. DOI: 10.1200/jco.2010.28.15_suppl.2541.Peer-Reviewed Original Research
2009
1205 A first-in-human Phase I study to evaluate the pan-PI3K inhibitor GDC-0941 administered QD or BID in patients with advanced solid tumours
Von Hoff D, Wagner A, LoRusso P, Tibes R, Jin J, Ware J, Yan Y, Derynck M, Dolezal M, Demetri G. 1205 A first-in-human Phase I study to evaluate the pan-PI3K inhibitor GDC-0941 administered QD or BID in patients with advanced solid tumours. European Journal Of Cancer Supplements 2009, 7: 122. DOI: 10.1016/s1359-6349(09)70417-3.Peer-Reviewed Original ResearchA 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 arm
2008
First in human phase I study of MK-2461, a small molecule inhibitor of c-Met, for patients with advanced solid tumors
Camacho L, Moulder S, LoRusso P, Blumenschein G, Bristow P, Kurzrock R, Fu S, Schlienger K, Bergstrom D. First in human phase I study of MK-2461, a small molecule inhibitor of c-Met, for patients with advanced solid tumors. Journal Of Clinical Oncology 2008, 26: 14657-14657. DOI: 10.1200/jco.2008.26.15_suppl.14657.Peer-Reviewed Original Research