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 activationEfficacy and safety of brigimadlin (BI 907828), an MDM2–p53 antagonist, in patients (pts) with advanced biliary tract cancer: Data from two phase Ia/Ib dose-escalation/expansion trials.
Yamamoto N, Tolcher A, Hafez N, Lugowska I, Ramlau R, Geng J, Li J, Teufel M, Maerten A, LoRusso P. Efficacy and safety of brigimadlin (BI 907828), an MDM2–p53 antagonist, in patients (pts) with advanced biliary tract cancer: Data from two phase Ia/Ib dose-escalation/expansion trials. Journal Of Clinical Oncology 2024, 42: 487-487. DOI: 10.1200/jco.2024.42.3_suppl.487.Peer-Reviewed Original ResearchBiliary tract cancerTreatment-related AEsAdvanced biliary tract cancerMonotherapy trialsStable diseasePartial responseCombination trialsMouse double minute 2MDM2-p53 antagonistsEscalating dosesSolid tumorsCases of biliary tract cancerTP53 wild-type tumorsAnti-PD-1 antibodyStandard-of-care chemotherapyData cut-offWild-type tumorsAdvanced/metastatic solid tumorsResponding ptsMDM2-p53MDM2 amplified tumorsDouble minute 2MDM2-amplifiedAmpullary adenocarcinomaCell cycle arrest
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 endpoint
2021
A phase I dose-escalation study of the MDM2-p53 antagonist BI 907828 in patients (pts) with advanced solid tumors.
LoRusso P, Gounder M, Patel M, Yamamoto N, Bauer T, Laurie S, Grempler R, Davenport T, Geng J, Rohrbacher M, Lahmar M. A phase I dose-escalation study of the MDM2-p53 antagonist BI 907828 in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2021, 39: 3016-3016. DOI: 10.1200/jco.2021.39.15_suppl.3016.Peer-Reviewed Original ResearchDose-limiting toxicityAdvanced solid tumorsArm AAdverse eventsArm BSolid tumorsDay 1Phase I dose-escalation studyExperienced dose-limiting toxicityNon-hematologic adverse eventsTreatment-related adverse eventsI dose-escalation studyAntitumor activityBiomarkers GDF-15Dose-escalation partGrade 3 nauseaManageable safety profileMDM2-p53 antagonistsPreliminary PK dataDose-escalation studyPatient-derived xenograftsClearance/FCycle 1Favorable PK propertiesLogistic regression models
2019
A phase Ia/Ib, open label, multicenter, dose-escalation study of BI 907828 (MDM2-p53 antagonist) in adult patients with advanced or metastatic solid tumors.
Chong C, Bauer T, Laurie S, Patel M, Yamamoto N, Davenport T, Geng J, Gibson N, Vallaster M, LoRusso P. A phase Ia/Ib, open label, multicenter, dose-escalation study of BI 907828 (MDM2-p53 antagonist) in adult patients with advanced or metastatic solid tumors. Journal Of Clinical Oncology 2019, 37: tps3166-tps3166. DOI: 10.1200/jco.2019.37.15_suppl.tps3166.Peer-Reviewed Original ResearchDose-limiting toxicityMetastatic solid tumorsFirst treatment cycleSolid tumorsEvaluable patientsPrimary endpointTreatment cyclesPhase 1bPreliminary anti-tumor activityMDM2-p53 antagonistsNon-squamous NSCLCDose-escalation studyDose-escalation trialSoft tissue sarcomasNumber of patientsTP53 wild-type statusWild-type statusAnti-tumor activityMDM2 amplification statusTumor protein 53New anti-cancer drugsIA/IBOpen labelRECIST v1.1Brain metastases