2024
Treatment of patients with dedifferentiated liposarcoma (DDLPS) with the MDM2–p53 antagonist brigimadlin and p53 function: A longitudinal analysis of circulating microRNAs (miRNAs) in a first-in-human phase Ia/Ib study.
Peltzer A, LoRusso P, Gounder M, Yamamoto N, Somaiah N, Lugowska I, Moreno V, Teufel M, Jayadeva G, Hesse R, Sturm G, Schöffski P. Treatment of patients with dedifferentiated liposarcoma (DDLPS) with the MDM2–p53 antagonist brigimadlin and p53 function: A longitudinal analysis of circulating microRNAs (miRNAs) in a first-in-human phase Ia/Ib study. Journal Of Clinical Oncology 2024, 42: 11540-11540. DOI: 10.1200/jco.2024.42.16_suppl.11540.Peer-Reviewed Original ResearchDedifferentiated liposarcomaP53 functionMDM2-p53Plasma samplesMiRNA analysisRestoration of p53 functionTranscription factor p53Phase Ia/Ib studyCox hazard ratio modelWild-type diseaseAdvanced solid tumorsDifferential expression analysisNext-generation sequencingBaseline plasma samplesTreatment of patientsMDM2-p53 antagonistsPlasma of patientsAnalysis of miRNAsTranscriptional regulationHsa-miR-92b-3pMDM2-amplifiedHazard ratio modelMiRNA expressionPharmacodynamic markersExpression analysisProteomic analysis in patients with dedifferentiated liposarcoma (DDLPS) in a phase Ia/Ib study of the MDM2–p53 antagonist brigimadlin.
Jaimes Y, LoRusso P, Sturm G, Gounder M, Yamamoto N, Somaiah N, Lugowska I, Moreno V, Peltzer A, Teufel M, Jayadeva G, Schöffski P. Proteomic analysis in patients with dedifferentiated liposarcoma (DDLPS) in a phase Ia/Ib study of the MDM2–p53 antagonist brigimadlin. Journal Of Clinical Oncology 2024, 42: 11541-11541. DOI: 10.1200/jco.2024.42.16_suppl.11541.Peer-Reviewed Original ResearchPhase Ia/Ib studyDedifferentiated liposarcomaDDLPS samplesTranscriptional regulation of target genesPlasma samplesPAI-1Angiopoietin-1Cycle 3 day 1Neutrophil gelatinase-associated lipocalin levelsC-C motif chemokine 5Regulation of target genesTumor suppressor p53Cox hazard ratio modelAdvanced solid tumorsProteomic analysis of plasma samplesRestore p53 activityAXL receptor tyrosine kinaseElevated GDF-15MDM2-p53 antagonistsReceptor tyrosine kinasesP53 targetsTranscriptional regulationHazard ratio modelMyelosuppression eventsP53 activation56O A phase Ia/Ib study of the MDM2-p53 antagonist brigimadlin (BI 907828): Safety and efficacy in patients with dedifferentiated liposarcoma
Schöffski P, Lorusso P, Yamamoto N, Reichardt P, Schwartz L, Dercle L, Zhao B, Chitalia R, Montgomery G, Hu C, Landsteiner H, Jayadeva G, Gounder M. 56O A phase Ia/Ib study of the MDM2-p53 antagonist brigimadlin (BI 907828): Safety and efficacy in patients with dedifferentiated liposarcoma. ESMO Open 2024, 9: 102446. DOI: 10.1016/j.esmoop.2024.102446.Peer-Reviewed Original ResearchDedifferentiated liposarcoma
2023
The MDM2–p53 antagonist BI 907828 in patients with advanced or metastatic solid tumors: results of a phase Ia, first-in-human, dose-escalation study
LoRusso P, Yamamoto N, Patel M, Laurie S, Bauer T, Geng J, Davenport T, Teufel M, Li J, Lahmar M, Gounder M. The MDM2–p53 antagonist BI 907828 in patients with advanced or metastatic solid tumors: results of a phase Ia, first-in-human, dose-escalation study. Cancer Discovery 2023, 13: 1802-1813. PMID: 37269344, PMCID: PMC10401071, DOI: 10.1158/2159-8290.cd-23-0153.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsSolid tumorsDay 1Common treatment-related adverse eventsGrowth differentiation factor-15 levelsMDM2-p53 antagonistsManageable safety profileAdvanced solid tumorsDose-escalation studyDose-limiting toxicityMetastatic solid tumorsDose-dependent increaseIA/IBAdverse eventsSafety profilePreliminary efficacyDedifferentiated liposarcomaClinical investigationCommon gradePatientsRelated commentaryIssue featureTarget engagementAntitumor activityTumorsA phase Ia/Ib, dose-escalation/expansion study of the MDM2–p53 antagonist BI 907828 in patients (pts) with solid tumors: Safety and efficacy in patients with dedifferentiated liposarcoma (DDLPS).
LoRusso P, Gounder M, Yamamoto N, Patel M, Bauer T, Geng J, Sailer R, Tang Y, Jayadeva G, Schöffski P. A phase Ia/Ib, dose-escalation/expansion study of the MDM2–p53 antagonist BI 907828 in patients (pts) with solid tumors: Safety and efficacy in patients with dedifferentiated liposarcoma (DDLPS). Journal Of Clinical Oncology 2023, 41: 11554-11554. DOI: 10.1200/jco.2023.41.16_suppl.11554.Peer-Reviewed Original ResearchTreatment-related AEsProgression-free survivalManageable safety profileOverall response rateDedifferentiated liposarcomaSafety profileCohort 1Day 1Phase IbSolid tumorsMedian progression-free survivalDisease control rateECOG PS 0/1MDM2-p53 antagonistsPrior systemic therapySmall intestine obstructionSubgroups of ptsAdvanced solid tumorsFirst-line treatmentPreclinical antitumor activityFast track designationIA/IBPS 0/1Serious AEsPrimary endpoint42O A phase Ia/b, dose-escalation and expansion study evaluating the MDM2–p53 antagonist BI 907828 in patients with solid tumours: Safety and efficacy in patients with dedifferentiated liposarcoma (DDLPS)
Schoeffski P, Yamamoto N, Bauer T, Patel M, Lorusso P, Lahmar M, Durland-Busbice S, Geng J, Gounder M. 42O A phase Ia/b, dose-escalation and expansion study evaluating the MDM2–p53 antagonist BI 907828 in patients with solid tumours: Safety and efficacy in patients with dedifferentiated liposarcoma (DDLPS). ESMO Open 2023, 8: 101079. DOI: 10.1016/j.esmoop.2023.101079.Peer-Reviewed Original ResearchA 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
2020
7LBA Late Breaking Milademetan, an oral MDM2 inhibitor, in well-differentiated/ dedifferentiated liposarcoma: results from a phase 1 study in patients with solid tumors or lymphomas
Gounder M, Bauer T, Schwartz G, LoRusso P, Kumar P, Kato K, Tao B, Hong Y, Patel P, Hong D. 7LBA Late Breaking Milademetan, an oral MDM2 inhibitor, in well-differentiated/ dedifferentiated liposarcoma: results from a phase 1 study in patients with solid tumors or lymphomas. European Journal Of Cancer 2020, 138: s3-s4. DOI: 10.1016/s0959-8049(20)31080-7.Peer-Reviewed Original Research