2024
Efficacy and Safety of the MDM2–p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced Biliary Tract Cancer: A Case Series
Yamamoto N, Tolcher A, Hafez N, Lugowska I, Ramlau R, Macarulla T, Geng J, Li J, Teufel M, Märten A, LoRusso P. Efficacy and Safety of the MDM2–p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced Biliary Tract Cancer: A Case Series. OncoTargets And Therapy 2024, 17: 267-280. PMID: 38567193, PMCID: PMC10986405, DOI: 10.2147/ott.s440979.Peer-Reviewed Original ResearchBiliary tract cancerAdvanced biliary tract cancerAdverse eventsDose reduction due to adverse eventsBiliary tract cancer casesChemotherapy plus immunotherapyPhase Ia/Ib trialPD-1 inhibitorsSecond-line optionAnti-tumor activityStable diseasePartial responsePD-1Treatment discontinuationCase seriesSafety profilePatientsImprove outcomesMolecular heterogeneityCancerMDM2-p53DiseaseImmunotherapyDoseEfficacyEfficacy 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.
Macarulla T, 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
Efficacy and safety of the MDM2–p53 antagonist BI 907828 in patients 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, Gounder M, Geng J, Li J, Teufel M, Maerten A, LoRusso P. Efficacy and safety of the MDM2–p53 antagonist BI 907828 in patients with advanced biliary tract cancer: Data from two phase Ia/Ib dose-escalation/expansion trials. Journal Of Clinical Oncology 2023, 41: 543-543. DOI: 10.1200/jco.2023.41.4_suppl.543.Peer-Reviewed Original ResearchAdvanced biliary tract cancerBiliary tract cancerTreatment-related AEsMost common gradeMonotherapy trialsCombination trialsStable diseaseTract cancerExpansion trialGallbladder carcinomaCommon gradeAnti-PD-1 antibodyWhite blood cell countManageable safety profileAdvanced solid tumorsBiliary tract adenocarcinomaBlood cell countRange of malignanciesPreclinical antitumor activityNegative prognostic markerPotential antitumor strategyAmpullary adenocarcinomaIIb trialAmpullary carcinomaSafety profile
2022
Dose escalation of a phase 1b/2 study of modakafusp alfa, an immune-targeting attenuated cytokine, in patients (pts) with metastatic solid tumors.
Johnson M, Abdul-Karim R, Sommerhalder D, Hafez N, Wang S, Li C, Liu Y, Yang L, Collins S, Parot X, Strauss J. Dose escalation of a phase 1b/2 study of modakafusp alfa, an immune-targeting attenuated cytokine, in patients (pts) with metastatic solid tumors. Journal Of Clinical Oncology 2022, 40: 2503-2503. DOI: 10.1200/jco.2022.40.16_suppl.2503.Peer-Reviewed Original ResearchTreatment-related adverse eventsMetastatic solid tumorsAnti-drug antibodiesPhase 1b/2 studySolid tumorsDose escalationAttenuated cytokineGrade 4 thrombocytopeniaManageable safety profileMedian prior linesPhase 2 doseStrong clinical responseDose-escalation phaseInfusion-related reactionsDose-limiting toxicityProof of mechanismPreclinical mouse modelsImmune cell activationDose range 0.1IgG4 monoclonal antibodyQ3W dosingStable diseaseCheckpoint inhibitorsRefractory/Adverse events
2020
CX-2029, a PROBODY drug conjugate targeting CD71 (transferrin receptor): Results from a first-in-human study (PROCLAIM-CX-2029) in patients (Pts) with advanced cancer.
Johnson M, El-Khoueiry A, Hafez N, Lakhani N, Mamdani H, Rodon Ahnert J, Sanborn R, Ho T, Li R, Waldes J, Spira A. CX-2029, a PROBODY drug conjugate targeting CD71 (transferrin receptor): Results from a first-in-human study (PROCLAIM-CX-2029) in patients (Pts) with advanced cancer. Journal Of Clinical Oncology 2020, 38: 3502-3502. DOI: 10.1200/jco.2020.38.15_suppl.3502.Peer-Reviewed Original ResearchTreatment-related AEsAntibody-drug conjugatesHuman studiesCommon treatment-related AEsTumor modelObserved safety profileInfusion-related reactionsPK/PD analysisAdvanced solid tumorsAnti-tumor activityXenograft tumor modelMedian molar ratiosMultiple xenograft tumor modelsTumor-associated proteasesECOG 0Dose cohortsStable diseasePartial responsePhase 1/2Systemic therapyAdvanced cancerDose escalationSafety profileGrade 3Ocular melanoma