2024
669P CBX-12-101: Final results of a phase I study of CBX-12, a peptide drug conjugate (PDC) in patients (pts) with metastatic solid tumors
Lorusso P, Meric-Bernstam F, Hafez N, Rivera I, Tripathy D, Wilks S, Pearson P, Needle M, Tolcher A. 669P CBX-12-101: Final results of a phase I study of CBX-12, a peptide drug conjugate (PDC) in patients (pts) with metastatic solid tumors. Annals Of Oncology 2024, 35: s525. DOI: 10.1016/j.annonc.2024.08.735.Peer-Reviewed Original ResearchA Relative Bioavailability, Bioequivalence, and Food Effect Study of Niraparib Tablets in Patients with Advanced Solid Tumors
Falchook G, Patnaik A, Richardson D, Harvey R, Sharma M, Hafez N, Hamilton E, Piha-Paul S, Barve M, Wise-Draper T, Patel M, Dowlati A, Pascuzzo J, Tang S, Faltermeier C, Malinowska I, Shtessel L, Striha A, Potocka E. A Relative Bioavailability, Bioequivalence, and Food Effect Study of Niraparib Tablets in Patients with Advanced Solid Tumors. Clinical Therapeutics 2024, 46: 228-238. PMID: 38423866, DOI: 10.1016/j.clinthera.2024.01.004.Peer-Reviewed Original ResearchHigh-fat mealFood effectPK parametersSolid tumorsGeometric least square meansAdvanced ovarian cancerAdvanced solid tumorsFood effect studyEstimate PK parametersSafety populationOpen-labelStandard therapyOvarian cancerPK variabilityFE stageMaintenance treatmentNiraparibDisease progressionSafety signalsTreatment periodInhibitor niraparibConcentration dataPatientsFasting stateCapsule formulationEfficacy 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
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 eventsA phase Ia/Ib, dose-escalation/expansion study of BI 907828 in combination with BI 754091 (ezabenlimab) and BI 754111 in patients (pts) with advanced solid tumors.
Yamamoto N, Hafez N, Tolcher A, Teufel M, Geng J, Svensson L, Lahmar M, Gounder M. A phase Ia/Ib, dose-escalation/expansion study of BI 907828 in combination with BI 754091 (ezabenlimab) and BI 754111 in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2022, 40: 3095-3095. DOI: 10.1200/jco.2022.40.16_suppl.3095.Peer-Reviewed Original ResearchDose-limiting toxicityImmune checkpoint inhibitorsDoublet combinationsCheckpoint inhibitorsPrimary endpointPhase Ia/Ib studySolid tumorsManageable safety profileMDM2-p53 antagonistsProgression-free survivalAdvanced solid tumorsBiliary tract carcinomaMetastatic solid tumorsSoft tissue sarcomasAnti-tumor effectsWild-type cancersAnti-tumor activityLogistic regression modelsPhase IaMultiple tumor typesG3 anemiaG3 neutropeniaG4 thrombocytopeniaIA/IBMurine double minuteKRYSTAL-1: Updated activity and safety of adagrasib (MRTX849) in patients (Pts) with unresectable or metastatic pancreatic cancer (PDAC) and other gastrointestinal (GI) tumors harboring a KRASG12C mutation.
Bekaii-Saab T, Spira A, Yaeger R, Buchschacher G, McRee A, Sabari J, Johnson M, Barve M, Hafez N, Velastegui K, Christensen J, Kheoh T, Der-Torossian H, Rybkin I. KRYSTAL-1: Updated activity and safety of adagrasib (MRTX849) in patients (Pts) with unresectable or metastatic pancreatic cancer (PDAC) and other gastrointestinal (GI) tumors harboring a KRASG12C mutation. Journal Of Clinical Oncology 2022, 40: 519-519. DOI: 10.1200/jco.2022.40.4_suppl.519.Peer-Reviewed Original ResearchDisease control rateKRAS G12C mutationProgression-free survivalPartial responseGI tumorsClinical activityG12C mutationPancreatic cancerSolid tumorsMedian progression-free survivalTreatment-related adverse eventsGrade 3/4 eventsGrade 5 eventsPhase 1/2 studyAdvanced solid tumorsMetastatic pancreatic cancerMetastatic solid tumorsEncouraging clinical activityPhase 2 cohortExtensive tissue distributionKRAS G12C inhibitorsFavorable pharmacokinetic propertiesEvaluable ptsKRASG12C mutationData cutoff
2020
A phase Ia/Ib, dose-escalation/expansion study of BI 907828 in combination with BI 754091 and BI 754111 in patients (pts) with advanced solid tumors.
Tolcher A, Hafez N, Yamamoto N, Park J, Grempler R, Lucarelli A, Lahmar M, Wang B, Gounder M. A phase Ia/Ib, dose-escalation/expansion study of BI 907828 in combination with BI 754091 and BI 754111 in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2020, 38: tps3660-tps3660. DOI: 10.1200/jco.2020.38.15_suppl.tps3660.Peer-Reviewed Original ResearchDose-limiting toxicityProgression-free survivalPrimary endpointSecondary endpointsPhase IbPhase Ia/Ib studySolid tumorsAnti-PD-1 antibodyMeasurable target lesionsAdvanced solid tumorsMaximum-tolerated doseFirst treatment cycleMetastatic solid tumorsAnti-LAG-3 antibodyTP53 wild-type tumorsAnti-tumor effectsWild-type cancersWild-type tumorsTP53 mutation statusLogistic regression modelsMultiple tumor typesEvaluable ptsIA/IBMurine double minutePFS rates