2022
Nivolumab plus radiotherapy with or without temozolomide in newly diagnosed glioblastoma: Results from exploratory phase I cohorts of CheckMate 143
Omuro A, Reardon DA, Sampson JH, Baehring J, Sahebjam S, Cloughesy TF, Chalamandaris AG, Potter V, Butowski N, Lim M. Nivolumab plus radiotherapy with or without temozolomide in newly diagnosed glioblastoma: Results from exploratory phase I cohorts of CheckMate 143. Neuro-Oncology Advances 2022, 4: vdac025. PMID: 35402913, PMCID: PMC8989388, DOI: 10.1093/noajnl/vdac025.Peer-Reviewed Original ResearchSafety/tolerabilityNew safety signalsOverall survivalCheckMate 143Median OSSafety signalsGrade 3/4 treatment-related adverse eventsTreatment-related adverse eventsEfficacy of nivolumabImmune checkpoint inhibitionMedian overall survivalPhase 1 cohortFirst-line treatmentPart APrimary endpointSecondary endpointsAdverse eventsCheckpoint inhibitionPatientsI cohortNivolumabTemozolomideRadiotherapyMonthsPart BPhase I/randomized phase II trial of TRC105 plus bevacizumab versus bevacizumab in recurrent glioblastoma: North Central Cancer Treatment Group N1174 (Alliance)
Galanis E, Anderson SK, Twohy E, Butowski NA, Hormigo A, Schiff D, Omuro A, Jaeckle KA, Kumar S, Kaufmann TJ, Geyer S, Kumthekar PU, Campian J, Giannini C, Buckner JC, Wen PY. Phase I/randomized phase II trial of TRC105 plus bevacizumab versus bevacizumab in recurrent glioblastoma: North Central Cancer Treatment Group N1174 (Alliance). Neuro-Oncology Advances 2022, 4: vdac041. PMID: 35664553, PMCID: PMC9154335, DOI: 10.1093/noajnl/vdac041.Peer-Reviewed Original ResearchProgression-free survivalRandomized phase II trialPhase II trialBevacizumab monotherapyRecurrent glioblastomaII trialTreatment armsMedian progression-free survivalLimited effective treatment optionsPhase IQuestionable survival benefitEarly clinical dataEffective treatment optionPhase IIQuality of lifeCombination armPrimary endpointAdverse eventsSurvival benefitLife scoresPoor prognosisTreatment optionsMechanisms of resistanceBevacizumabClinical data
2021
CTIM-25. A RANDOMIZED PHASE 3 STUDY OF NIVOLUMAB OR PLACEBO COMBINED WITH RADIOTHERAPY PLUS TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA WITH METHYLATED MGMT PROMOTER: CHECKMATE 548
Weller M, Lim M, Idbaih A, Steinbach J, Finocchiaro G, Raval R, Ashby L, Ansstas G, Baehring J, Taylor J, Honnorat J, Petrecca K, de Vos F, Wick A, Sumrall A, Roberts M, Slepetis R, Warad D, Lee M, Reardon D, Omuro A. CTIM-25. A RANDOMIZED PHASE 3 STUDY OF NIVOLUMAB OR PLACEBO COMBINED WITH RADIOTHERAPY PLUS TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA WITH METHYLATED MGMT PROMOTER: CHECKMATE 548. Neuro-Oncology 2021, 23: vi55-vi56. PMCID: PMC8598415, DOI: 10.1093/neuonc/noab196.217.Peer-Reviewed Original ResearchProgression-free survivalMedian overall survivalPhase 3 studyOverall survivalMGMT promoterBaseline corticosteroidsMedian progression-free survivalTreatment-related adverse eventsRandomized phase 3 studyTumor PD-L1 expressionBlinded independent central reviewDual primary endpointsRole of immunotherapyNew safety signalsPD-L1 expressionPositive prognostic factorIndependent central reviewPredictors of benefitCare radiotherapyTreatment landscapeAdverse eventsPrognostic factorsCentral reviewNivolumabNovel therapies
2020
Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma
Reardon DA, Brandes AA, Omuro A, Mulholland P, Lim M, Wick A, Baehring J, Ahluwalia MS, Roth P, Bähr O, Phuphanich S, Sepulveda JM, De Souza P, Sahebjam S, Carleton M, Tatsuoka K, Taitt C, Zwirtes R, Sampson J, Weller M. Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma. JAMA Oncology 2020, 6: 1003-1010. PMID: 32437507, PMCID: PMC7243167, DOI: 10.1001/jamaoncol.2020.1024.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAngiogenesis InhibitorsAntineoplastic Agents, ImmunologicalBevacizumabBrain NeoplasmsDNA Modification MethylasesDNA Repair EnzymesFemaleGlioblastomaHumansImmune Checkpoint InhibitorsMaleMiddle AgedNeoplasm Recurrence, LocalNivolumabProgrammed Cell Death 1 ReceptorTemozolomideTreatment OutcomeTumor Suppressor ProteinsYoung AdultConceptsTreatment-related adverse eventsPhase 3 clinical trialsPrimary end pointOverall survivalRecurrent glioblastomaClinical trialsMedian OSGrade 3/4 treatment-related adverse eventsRandomized phase 3 clinical trialSingle-agent PD-1 blockadeEnd pointEffects of nivolumabUnacceptable toxic effectsMedian overall survivalObjective response ratePD-1 blockadeOverall patient populationImmune checkpoint blockadeData cutoffAdverse eventsCheckpoint blockadeFirst recurrenceInhibitor therapyClinical outcomesSafety profile
2019
Complications associated with immunotherapy for brain metastases.
Tran TT, Jilaveanu LB, Omuro A, Chiang VL, Huttner A, Kluger HM. Complications associated with immunotherapy for brain metastases. Current Opinion In Neurology 2019, 32: 907-916. PMID: 31577604, PMCID: PMC7398556, DOI: 10.1097/wco.0000000000000756.Peer-Reviewed Original ResearchConceptsBrain metastasesNeurologic toxicityImmune therapyPhase 2 clinical trialCheckpoint inhibitor therapyImmune checkpoint inhibitorsMultiple phase 2 clinical trialsTreatment-related morbidityBrain metastatic diseaseSymptomatic edemaCheckpoint inhibitorsAdverse eventsDurable responsesMedian survivalMetastatic diseaseInhibitor therapyMore patientsIntracranial activityPatient groupRadiation necrosisClinical trialsTherapy trialsMultidisciplinary teamMetastasisPatientsBuparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial
Wen PY, Touat M, Alexander BM, Mellinghoff IK, Ramkissoon S, McCluskey CS, Pelton K, Haidar S, Basu SS, Gaffey SC, Brown LE, Martinez-Ledesma JE, Wu S, Kim J, Wei W, Park MA, Huse JT, Kuhn JG, Rinne ML, Colman H, Agar NYR, Omuro AM, DeAngelis LM, Gilbert MR, de Groot JF, Cloughesy TF, S. A, Roberts TM, Zhao JJ, Lee EQ, Nayak L, Heath JR, Horky LL, Batchelor TT, Beroukhim R, Chang SM, Ligon AH, Dunn IF, Koul D, Young GS, Prados MD, Reardon DA, Yung WKA, Ligon KL. Buparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial. Journal Of Clinical Oncology 2019, 37: jco.18.01207. PMID: 30715997, PMCID: PMC6553812, DOI: 10.1200/jco.18.01207.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAminopyridinesAntineoplastic AgentsBrain NeoplasmsChemotherapy, AdjuvantDisease ProgressionEnzyme ActivationFemaleGlioblastomaHumansMaleMiddle AgedMorpholinesNeoadjuvant TherapyNeoplasm Recurrence, LocalPhosphatidylinositol 3-KinasePhosphoinositide-3 Kinase InhibitorsProgression-Free SurvivalTime FactorsConceptsPhase II trialCohort 2Cohort 1PI3K pathwayTumor tissueII trialRecurrent glioblastomaBrain penetrationPan-PI3K inhibitor buparlisibPathway inhibitionPathway activationCommon grade 3K pathwayPrimary end pointGreater adverse eventsProgression-free survivalPI3K pathway inhibitionPI3K pathway activationPlasma drug levelsSingle-agent efficacySignificant brain penetrationPI3K inhibitorsMedian PFSOpen labelAdverse events
2017
Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143
Omuro A, Vlahovic G, Lim M, Sahebjam S, Baehring J, Cloughesy T, Voloschin A, Ramkissoon SH, Ligon KL, Latek R, Zwirtes R, Strauss L, Paliwal P, Harbison CT, Reardon DA, Sampson JH. Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143. Neuro-Oncology 2017, 20: 674-686. PMID: 29106665, PMCID: PMC5892140, DOI: 10.1093/neuonc/nox208.Peer-Reviewed Original ResearchConceptsAdverse eventsRecurrent glioblastomaCommon treatment-related adverse eventsTreatment-related adverse eventsDeath ligand 1 (PD-L1) expressionEffects of nivolumabExploratory efficacy outcomesSafety/tolerabilityFindings merit further investigationLigand 1 expressionCheckMate 143Ipilimumab doseNivolumab monotherapyStable diseaseAlternative regimenEfficacy outcomesRadiographic progressionMost patientsPartial responseNivolumabIpilimumabMerit further investigationPatientsI cohortFurther evaluationUpdated results of single-agent ibrutinib in recurrent/refractory primary (PCNSL) and secondary CNS lymphoma (SCNSL).
Grommes C, Gavrilovic I, Kaley T, Nolan C, Omuro A, Wolfe J, Pentsova E, Hatzoglou V, Mellinghoff I, DeAngelis L. Updated results of single-agent ibrutinib in recurrent/refractory primary (PCNSL) and secondary CNS lymphoma (SCNSL). Journal Of Clinical Oncology 2017, 35: 7515-7515. DOI: 10.1200/jco.2017.35.15_suppl.7515.Peer-Reviewed Original ResearchSecondary CNS lymphomaProgression-free survivalMedian progression-free survivalALT elevationCNS lymphomaAdverse eventsClinical responseGrade 4 adverse eventsRecurrent/refractory diseaseAggressive primary brain tumorCerebrospinal fluid involvementCNS lymphoma patientsGrade 5 eventsManageable adverse eventsGrade 3 toxicityMedian overall survivalMethotrexate-based chemotherapyEnd-organ functionNormal end-organ functionSingle-agent ibrutinibUrinary tract infectionPrimary brain tumorsPromising clinical responsesMantle cell lymphomaCommon toxicitiesMulticenter phase II study of temozolomide and myeloablative chemotherapy with autologous stem cell transplant for newly diagnosed anaplastic oligodendroglioma
Thomas AA, Abrey LE, Terziev R, Raizer J, Martinez NL, Forsyth P, Paleologos N, Matasar M, Sauter CS, Moskowitz C, Nimer SD, DeAngelis LM, Kaley T, Grimm S, Louis DN, Cairncross JG, Panageas KS, Briggs S, Faivre G, Mohile NA, Mehta J, Jonsson P, Chakravarty D, Gao J, Schultz N, Brennan CW, Huse JT, Omuro A. Multicenter phase II study of temozolomide and myeloablative chemotherapy with autologous stem cell transplant for newly diagnosed anaplastic oligodendroglioma. Neuro-Oncology 2017, 19: 1380-1390. PMID: 28472509, PMCID: PMC5596171, DOI: 10.1093/neuonc/nox086.Peer-Reviewed Original ResearchConceptsAutologous stem cell transplantProgression-free survivalHigh-dose chemotherapyStem cell transplantAnaplastic oligodendrogliomaAnaplastic oligoastrocytomaHDC-ASCTMulticenter phase II studyMyeloablative high-dose chemotherapyChemotherapy-based approachesCycles of temozolomideOverall survival 93Phase II studyRadiation-related toxicityUnexpected adverse eventsNext-generation sequencingChemotherapy-sensitive tumorsWide molecular heterogeneityToxic deathsAdverse eventsII studyMyeloablative chemotherapyProspective trialIntact patientsCell transplantOS07.3 Nivolumab in Combination With Radiotherapy With or Without Temozolomide in Patients With Newly Diagnosed Glioblastoma: Updated Results From CheckMate 143
Omuro A, Vlahovic G, Baehring J, Butowski N, Reardon D, Cloughesy T, Sahebjam S, Lim M, Zwirtes R, Sampson J. OS07.3 Nivolumab in Combination With Radiotherapy With or Without Temozolomide in Patients With Newly Diagnosed Glioblastoma: Updated Results From CheckMate 143. Neuro-Oncology 2017, 19: iii13-iii13. PMCID: PMC5463686, DOI: 10.1093/neuonc/nox036.044.Peer-Reviewed Original ResearchTreatment-related AEsAdverse eventsCheckMate 143Standard radiotherapyDisease progressionFirst prospective clinical trialHerpes simplex virus encephalitisTreatment-related adverse eventsTolerability of nivolumabTreatment-related deathsImmune checkpoint inhibitorsSimplex virus encephalitisDeath-1 receptorNew safety signalsPhase 2/3 studyProspective clinical trialsImmune cell infiltrationNovel therapeutic optionsMonoclonal antibody inhibitorMultiple cancer typesConcurrent temozolomideUnmethylated MGMTAdjuvant temozolomideCheckpoint inhibitorsRadiographic progression
2016
Single-Agent Ibrutinib in Recurrent/Refractory Central Nervous System Lymphoma
Grommes C, Pastore A, Gavrilovic I, Kaley T, Nolan C, Omuro A, Wolfe J, Pentsova E, Hatzoglou V, Mellinghoff I, DeAngelis L. Single-Agent Ibrutinib in Recurrent/Refractory Central Nervous System Lymphoma. Blood 2016, 128: 783. DOI: 10.1182/blood.v128.22.783.783.Peer-Reviewed Original ResearchPrimary central nervous system lymphomaProgression-free survivalSecondary CNS lymphomaMedian progression-free survivalHigh-dose methotrexate chemotherapyCentral nervous system lymphomaNervous system lymphomaAdverse eventsCNS lymphomaCombination armClinical responseMethotrexate chemotherapySystem lymphomaGrade 4 adverse eventsRecurrent/refractory diseaseAggressive primary brain tumorCerebrospinal fluid involvementCNS lymphoma patientsManageable adverse eventsGrade 3 toxicityMethotrexate-based chemotherapyEnd-organ functionNormal end-organ functionUrinary tract infectionPrimary brain tumorsATIM-16. NIVOLUMAB COMBINED WITH RADIOTHERAPY WITH OR WITHOUT TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA: RESULTS FROM PHASE 1 SAFETY COHORTS IN CHECKMATE 143
Omuro A, Vlahovic G, Baehring J, Butowski N, Reardon D, Cloughesy T, Sahebjam S, Lim M, Strauss L, Latek R, Zwirtes R, Paliwal P, Harbison C, Sampson J. ATIM-16. NIVOLUMAB COMBINED WITH RADIOTHERAPY WITH OR WITHOUT TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA: RESULTS FROM PHASE 1 SAFETY COHORTS IN CHECKMATE 143. Neuro-Oncology 2016, 18: vi21-vi21. DOI: 10.1093/neuonc/now212.081.Peer-Reviewed Original ResearchAdverse eventsCheckMate 143Frequent treatment-related adverse eventsTreatment-related serious adverse eventsFirst prospective clinical trialProgression/unacceptable toxicityTreatment-related adverse eventsCombination of nivolumabTolerability of nivolumabSerious adverse eventsDeath-1 receptorProspective clinical trialsNew safety concernsMonoclonal antibody inhibitorMultiple cancer typesMeasurable diseaseNivolumab CombinedSafety cohortToxic deathsTumor flareRadiographic progressionTreatment discontinuationMost patientsUnacceptable toxicityPoor prognosis
2015
Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non–small cell lung cancer
Nayak L, DeAngelis LM, Robins HI, Govindan R, Gadgeel S, Kelly K, Rigas JR, Peereboom DM, Rosenfeld SS, Muzikansky A, Zheng M, Urban P, Abrey LE, Omuro A, Wen PY. Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non–small cell lung cancer. Cancer 2015, 121: 4165-4172. PMID: 26308485, PMCID: PMC5941922, DOI: 10.1002/cncr.29636.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerProgressive brain metastasesBrain metastasesCell lung cancerAdverse eventsStudy drugLung cancerGrade 3/4 adverse eventsMulticenter phase 2 studyNSCLC brain metastasesSteady-state distribution volumePhase 1/2 studyRecurrent brain metastasesPhase 2 studyProgression-free survivalFirst prospective studyConcentration-time curvePrimary endpointAdult patientsOverall survivalPulmonary embolismMedian agePeripheral neuropathyMedian timeProspective studyPhase I dose-escalation study of the PI3K/mTOR inhibitor voxtalisib (SAR245409, XL765) plus temozolomide with or without radiotherapy in patients with high-grade glioma
Wen PY, Omuro A, Ahluwalia MS, Fathallah-Shaykh HM, Mohile N, Lager JJ, Laird AD, Tang J, Jiang J, Egile C, Cloughesy TF. Phase I dose-escalation study of the PI3K/mTOR inhibitor voxtalisib (SAR245409, XL765) plus temozolomide with or without radiotherapy in patients with high-grade glioma. Neuro-Oncology 2015, 17: 1275-1283. PMID: 26019185, PMCID: PMC4588757, DOI: 10.1093/neuonc/nov083.Peer-Reviewed Original ResearchConceptsHigh-grade gliomasAdverse eventsRadiation therapySkin biopsiesPhase I dose-escalation studyTreatment-related adverse eventsI dose-escalation studyPI3K/mTOR pathway inhibitionTreatment-related gradeDose-escalation studyDose-escalation designFavorable safety profileMTOR pathway inhibitionEvaluable patientsStable diseasePartial responsePharmacodynamic effectsPlatelet countRapamycin inhibitorsSafety profilePreliminary efficacyTumor responsePlasma pharmacokineticsVoxtalisibPatients
2014
AT-35INTERMITTENT HIGH DOSE (PULSATILE) ERLOTINIB FOR EGFRvIII MUTANT RECURRENT MALIGNANT GLIOMAS: A PILOT CLINICAL TRIAL
Lassman A, Grommes C, Panageas K, Iwamoto F, DeAngelis L, Kaley T, Gavrilovic I, Pentsova E, Omuro A, Corpuz C, Briggs S, Otap D, Qin W, Cross J, Mellinghoff I. AT-35INTERMITTENT HIGH DOSE (PULSATILE) ERLOTINIB FOR EGFRvIII MUTANT RECURRENT MALIGNANT GLIOMAS: A PILOT CLINICAL TRIAL. Neuro-Oncology 2014, 16: v16-v16. PMCID: PMC4217814, DOI: 10.1093/neuonc/nou237.35.Peer-Reviewed Original ResearchRecurrent malignant gliomaMalignant gliomasInhibitor therapyHigh-dose erlotinibOngoing complete responseEGFR-TKI erlotinibPopulation of patientsMedian age 58Pilot clinical trialInadequate drug deliveryKinase inhibitor therapyDose erlotinibEligible patientsPulsatile dosingAdverse eventsMedian survivalComplete responseDaily doseTKI erlotinibMedian CmaxAnaplastic gliomasClinical trialsAge 58Surgical armLimited efficacy
2013
A phase I study of carboxyamidotriazole orotate (CTO) in of advanced solid tumors.
Sandler A, Taylor M, Urba W, Omuro A, Anderson B, Hansen D, Fisher B, Claeys A, Greathouse A, McLean S, Karmali R. A phase I study of carboxyamidotriazole orotate (CTO) in of advanced solid tumors. Journal Of Clinical Oncology 2013, 31: 2518-2518. DOI: 10.1200/jco.2013.31.15_suppl.2518.Peer-Reviewed Original ResearchAdvanced solid tumorsCell lung cancerStable diseaseLung cancerSolid tumorsSquamous cell lung cancerSmall cell lung cancerAdequate organ functionGrade 3 fatigueCreatine kinase elevationSquamous cell carcinomaColon tumor xenograftsAnti-tumor effectsAnti-invasive propertiesPharmacokinetic samplingAdverse eventsQTc prolongationCell carcinomaTumor responseEGFR mutationsPIK3CA mutationsMalignant gliomasLung adenocarcinomaTumor assessmentCT scan
2011
A phase II study of the Ras-MAPK signaling pathway inhibitor TLN-4601 in patients with glioblastoma at first progression
Mason WP, Belanger K, Nicholas G, Vallières I, Mathieu D, Kavan P, Desjardins A, Omuro A, Reymond D. A phase II study of the Ras-MAPK signaling pathway inhibitor TLN-4601 in patients with glioblastoma at first progression. Journal Of Neuro-Oncology 2011, 107: 343-349. PMID: 22048878, DOI: 10.1007/s11060-011-0747-6.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsBrain NeoplasmsChromatography, LiquidDibenzazepinesErbB ReceptorsFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticGlioblastomaHumansInfusions, IntraventricularKaplan-Meier EstimateMagnetic Resonance ImagingMaleMiddle AgedPTEN PhosphohydrolaseTandem Mass SpectrometryConceptsPharmacokinetic evaluationProgressive glioblastomaFirst progressionM2/dayPhase II studyMR scansPhase II trialContinuous intravenous administrationBlood-brain barrierLack of efficacyPeripheral benzodiazepine receptorEvaluable patientsStable diseaseII trialRadiographic progressionAdverse eventsII studyRecurrent glioblastomaDisease progressionDrug levelsIntravenous administrationBiomarker assessmentPatientsAnimal modelsBenzodiazepine receptors