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
2017
A call for global harmonization of phase I oncology trials: Results from two parallel, first-in-human phase I studies of DS-7423, an oral PI3K/mTOR dual inhibitor in advanced solid tumors conducted in the United States and Japan.
Yokota T, Bendell J, LoRusso P, Tsushima T, Desai V, Kenmotsu H, Watanabe J, Ono A, Murugesan B, Silva J, Naito T, Greenberg J, Kumar P, Wang Y, Jikoh T, Shiga R, Ho A, Gounder M. A call for global harmonization of phase I oncology trials: Results from two parallel, first-in-human phase I studies of DS-7423, an oral PI3K/mTOR dual inhibitor in advanced solid tumors conducted in the United States and Japan. Journal Of Clinical Oncology 2017, 35: 2536-2536. DOI: 10.1200/jco.2017.35.15_suppl.2536.Peer-Reviewed Original ResearchMaximum-tolerated doseBody mass indexAdvanced solid tumorsBody weightPhase IFrequent treatment-related adverse eventsSolid tumorsNon-small cell lung cancerGrade 3 lung infectionHuman Phase I StudyTreatment-related adverse eventsCorresponding phase IGrade 3 dehydrationGrade 3 fatigueGrade 3 stomatitisGrade 4 hyperglycemiaPhase 2 doseGrade 3 rashCell lung cancerPhase I studiesSquamous cell carcinomaPI3K/mTOR dual inhibitorPI3K/mTORMTOR dual inhibitorStable disease
2016
Preclinical and first‐in‐human phase I studies of KW‐2450, an oral tyrosine kinase inhibitor with insulin‐like growth factor receptor‐1/insulin receptor selectivity
Schwartz GK, Dickson MA, LoRusso P, Sausville EA, Maekawa Y, Watanabe Y, Kashima N, Nakashima D, Akinaga S. Preclinical and first‐in‐human phase I studies of KW‐2450, an oral tyrosine kinase inhibitor with insulin‐like growth factor receptor‐1/insulin receptor selectivity. Cancer Science 2016, 107: 499-506. PMID: 26850678, PMCID: PMC4832855, DOI: 10.1111/cas.12906.Peer-Reviewed Original ResearchConceptsOral tyrosine kinase inhibitorTyrosine kinase inhibitorsIGF-1RSolid tumorsHuman Phase I StudyInsulin-like growth factor receptor 1Colon carcinoma xenograft modelKinase inhibitorsHuman epidermal growth factor receptorPhase I clinical trialDose of KWModest antitumor activityAdvanced solid tumorsMetastatic breast cancerPhase I studiesGrowth factor receptor 1Human IGF-1RHuman malignant cell linesEpidermal growth factor receptorFactor receptor 1Inhibitory activityEvaluable patientsGrowth factor receptorMalignant cell linesStable disease