2024
ONC201 (Dordaviprone) in Recurrent H3 K27M–Mutant Diffuse Midline Glioma
Arrillaga-Romany I, Gardner S, Odia Y, Aguilera D, Allen J, Batchelor T, Butowski N, Chen C, Cloughesy T, Cluster A, de Groot J, Dixit K, Graber J, Haggiagi A, Harrison R, Kheradpour A, Kilburn L, Kurz S, Lu G, MacDonald T, Mehta M, Melemed A, Nghiemphu P, Ramage S, Shonka N, Sumrall A, Tarapore R, Taylor L, Umemura Y, Wen P. ONC201 (Dordaviprone) in Recurrent H3 K27M–Mutant Diffuse Midline Glioma. Journal Of Clinical Oncology 2024, 42: 1542-1552. PMID: 38335473, PMCID: PMC11095894, DOI: 10.1200/jco.23.01134.Peer-Reviewed Original ResearchConceptsH3 K27M-mutant diffuse midline gliomaDiffuse midline gliomaDuration of responseTime to responseHigh-grade gliomasLow-grade gliomasMidline gliomaMedian duration of responseMedian time to responseTreatment-emergent adverse eventsEnd pointsBlinded independent central reviewCorticosteroid dose reductionIndependent central reviewSecondary end pointsClinically meaningful efficacyRadiographic end pointsSpinal tumorsDose reductionDismal prognosisCentral reviewPerformance scoresCorticosteroid responseResponse assessmentAdverse events
2022
Activity of Adagrasib (MRTX849) in Brain Metastases: Preclinical Models and Clinical Data From Patients With KRASG12C-Mutant Non-Small Cell Lung CancerPreliminary Activity of Adagrasib in Brain Metastases
Sabari J, Velcheti V, Shimizu K, Strickland M, Heist R, Singh M, Nayyar N, Giobbie-Hurder A, Digumarthy S, Gainor J, Rajan A, Nieblas-Bedolla E, Burns A, Hallin J, Olson P, Christensen J, Kurz S, Brastianos P, Wakimoto H. Activity of Adagrasib (MRTX849) in Brain Metastases: Preclinical Models and Clinical Data From Patients With KRASG12C-Mutant Non-Small Cell Lung CancerPreliminary Activity of Adagrasib in Brain Metastases. Clinical Cancer Research 2022, 28: 3318-3328. PMID: 35404402, PMCID: PMC9662862, DOI: 10.1158/1078-0432.ccr-22-0383.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerKRAS-mutant non-small cell lung cancerBrain metastasesCerebrospinal fluidAntitumor activityUntreated BMCentral nervous system penetrationDose-dependent pharmacokineticsCell lung cancerKRASG12C inhibitorsPreliminary clinical dataRetrospective database queryCerebrospinal fluid concentrationsPharmacokinetic propertiesExtensive tissue distributionTumor regressionNSCLC xenograftsPreclinical modelsPoor prognosisPreclinical studiesAdagrasibExtended survivalLung cancerClinical dataLong half-life