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
2011
Clinical combination of the MEK inhibitor GDC-0973 and the PI3K inhibitor GDC-0941: A first-in-human phase Ib study testing daily and intermittent dosing schedules in patients with advanced solid tumors.
Shapiro G, LoRusso P, Kwak E, Cleary J, Musib L, Jones C, de Crespigny A, Belvin M, McKenzie M, Gates M, Chan I, Bendell J. Clinical combination of the MEK inhibitor GDC-0973 and the PI3K inhibitor GDC-0941: A first-in-human phase Ib study testing daily and intermittent dosing schedules in patients with advanced solid tumors. Journal Of Clinical Oncology 2011, 29: 3005-3005. DOI: 10.1200/jco.2011.29.15_suppl.3005.Peer-Reviewed Original Research
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 trial