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
484 Preliminary efficacy of the IL-15 superagonist SO-C101 in combination with pembrolizumab in patients with advanced/metastatic solid tumors
Garralda E, Galvao V, Champiat S, LoRusso P, Grell P, Naing A, Janku F, Sachse R, Bechard D, Kiemle-Kallee J, Marabelle A, Garralda E. 484 Preliminary efficacy of the IL-15 superagonist SO-C101 in combination with pembrolizumab in patients with advanced/metastatic solid tumors. Journal For ImmunoTherapy Of Cancer 2021, 9: a514-a514. DOI: 10.1136/jitc-2021-sitc2021.484.Peer-Reviewed Original ResearchStudy drug-related adverse eventsDrug-related adverse eventsCytokine release syndromeDose-limiting toxicityAdverse eventsCommon study drug-related adverse eventsAnti-programmed cell death protein 1 antibodyGrade 3 cytokine release syndromeSolid tumorsCell death protein 1 antibodyAnti-PD-1 therapyLong-term stable diseaseLocal injection site reactionsSkin squamous cell carcinomaPhase 2 dosePrevious systemic therapyTreatment-related deathsInjection site reactionsMetastatic solid tumorsAdditional clinical benefitDose-escalation designProtective memory responsesProtein 1 antibodySquamous cell carcinomaAvailable safety data502 Recommended phase 2 dose, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the IL-15 superagonist SO-C101 as monotherapy in patients with advanced/metastatic solid tumors
Marabelle A, Champiat S, Galvao V, Naing A, Janku F, LoRusso P, Grell P, Sachse R, Bechard D, Kiemle-Kallee J, Garralda E. 502 Recommended phase 2 dose, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the IL-15 superagonist SO-C101 as monotherapy in patients with advanced/metastatic solid tumors. 2021, a534-a534. DOI: 10.1136/jitc-2021-sitc2021.502.Peer-Reviewed Original ResearchPhase 2 doseDose-limiting toxicityAdverse eventsPartial responseStable diseaseTransaminase increaseSolid tumorsDrug-related adverse eventsIL-15 receptor αCutaneous squamous cell carcinomaLocal injection site reactionsPrevious systemic therapyResults Thirty patientsSignificant partial responseTreatment-related deathsCommon adverse eventsFlu-like syndromeRelated adverse eventsInjection site reactionsMetastatic solid tumorsAdditional clinical benefitDose-escalation designSquamous cell carcinomaDose-dependent increaseT cell activation
2020
A 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
2018
A phase I dose-escalation and dose-expansion study of brontictuzumab in subjects with selected solid tumors
Ferrarotto R, Eckhardt G, Patnaik A, LoRusso P, Faoro L, Heymach J, Kapoun A, Xu L, Munster P. A phase I dose-escalation and dose-expansion study of brontictuzumab in subjects with selected solid tumors. Annals Of Oncology 2018, 29: 1561-1568. PMID: 29726923, DOI: 10.1093/annonc/mdy171.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntineoplastic Agents, ImmunologicalCohort StudiesDose-Response Relationship, DrugDrug Resistance, NeoplasmFemaleFollow-Up StudiesHumansMaleMaximum Tolerated DoseMiddle AgedNeoplasm Recurrence, LocalNeoplasmsPrognosisReceptor, Notch1Salvage TherapySurvival RateTissue DistributionConceptsNotch1 pathway activationPartial responseSolid tumorsPathway activationAdverse eventsCommon drug-related adverse eventsDrug-related adverse eventsDose-expansion studyGrade 3 diarrheaGrade 3 fatigueUnconfirmed partial responseRefractory solid tumorsProlonged SDsDisease stabilizationExpansion cohortMain toxicityRECIST 1.1Dose escalationEfficacy signalsClinical benefitPharmacodynamic effectsPreliminary efficacyAssessable subjectsImmunohistochemistry assaysNonlinear pharmacokinetics
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