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
2019
Single agent ONC201 in adult recurrent H3 K27M-mutant glioma.
Arrillaga I, Kurz S, Sumrall A, Butowski N, Harrison R, De Groot J, Shonka N, Lieberman F, Odia Y, Tarapore R, Merdinger K, Allen J, Oster W, Mehta M, Cloughesy T, Chi A, Lassman A, Batchelor T, Wen P. Single agent ONC201 in adult recurrent H3 K27M-mutant glioma. Journal Of Clinical Oncology 2019, 37: 3005-3005. DOI: 10.1200/jco.2019.37.15_suppl.3005.Peer-Reviewed Original ResearchH3 K27M-mutant gliomasResponse of stable diseaseStable diseaseMedian followTumor regressionTreatment discontinuation due to toxicitySingle agentDiscontinued due to toxicityMedian prior linesDose-limiting toxicityTreated with single agentsCompassionate use protocolProgression-freePrior radiationPartial responseConfirmatory scanDRD2 antagonistsMedian ageAssociated with improvementsProgressive diseaseTumor lesionsOn-treatmentAdult patientsPoor prognosisNeurological symptoms