2023
Multicenter Phase 2 Trial of the PARP Inhibitor Olaparib in Recurrent IDH1 and IDH2-Mutant Glioma
Fanucci K, Pilat M, Shyr D, Shyr Y, Boerner S, Li J, Durecki D, Drappatz J, Puduvalli V, Lieberman F, Gonzalez J, Giglio P, Ivy S, Bindra R, Omuro A, LoRusso P. Multicenter Phase 2 Trial of the PARP Inhibitor Olaparib in Recurrent IDH1 and IDH2-Mutant Glioma. Cancer Research Communications 2023, 3: 192-201. PMID: 36968138, PMCID: PMC10035510, DOI: 10.1158/2767-9764.crc-22-0436.Peer-Reviewed Original ResearchConceptsProgression-free survivalMedian progression-free survivalProlonged stable diseaseStable diseasePhase II trialGrade 4 tumorsII trialOlaparib monotherapyGrade 2Multicenter phase 2 trialSingle-arm phase II trialWorld Health Organization classificationMedian overall survivalNeuro-Oncology criteriaPhase 2 trialOverall response rateFuture patient stratificationMutant gliomasPARP inhibitor olaparibEvaluable patientsPrimary endpointOverall survivalProgressive diseaseSelect patientsClinical benefit
2022
Multicenter phase 2 trial of the PARP inhibitor (PARPi) olaparib in recurrent IDH1 and IDH2-mutant contrast-enhancing glioma.
Fanucci K, Pilat M, Shah R, Boerner S, Li J, Durecki D, Drappatz J, Collichio F, Puduvalli V, Lieberman F, Gonzalez J, Giglio P, Bao X, Ivy S, Bindra R, Omuro A, LoRusso P. Multicenter phase 2 trial of the PARP inhibitor (PARPi) olaparib in recurrent IDH1 and IDH2-mutant contrast-enhancing glioma. Journal Of Clinical Oncology 2022, 40: 2035-2035. DOI: 10.1200/jco.2022.40.16_suppl.2035.Peer-Reviewed Original ResearchProgression-free survivalMedian progression-free survivalStable diseaseDuration of responseOverall response ratePARP inhibitorsOverall survivalStandard therapyOlaparib monotherapyMulticenter phase 2 trialCDKN2A deletionClinical predictive markersGrade 3 lymphopeniaProlonged stable diseasePhase 2 trialGrade 4 tumorsFuture patient stratificationRecent preclinical studiesHigh-grade gliomasNovel drug combinationsContrast-enhancing gliomasEligible ptsEvaluable ptsRecent histologyPrimary endpoint
2018
Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma
Tun HW, Johnston PB, DeAngelis LM, Atherton PJ, Pederson LD, Koenig PA, Reeder CB, Omuro AMP, Schiff D, O'Neill B, Pulido J, Jaeckle KA, Grommes C, Witzig TE. Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma. Blood 2018, 132: 2240-2248. PMID: 30262659, PMCID: PMC6265643, DOI: 10.1182/blood-2018-02-835496.Peer-Reviewed Original ResearchConceptsPrimary central nervous system lymphomaOverall response ratePrimary vitreoretinal lymphomaProgression-free survivalRefractory primary central nervous system lymphomaComplete responsePartial responseVitreoretinal lymphomaGrade 3/4 hematologic toxicitiesGrade 3/4 nonhematologic toxicitiesMedian progression-free survivalCentral nervous system lymphomaDose escalation schedulePhase 1 studyNervous system lymphomaCombination of pomalidomideSignificant therapeutic activityMTD cohortNonhematologic toxicityHematologic toxicityRespiratory failureSystem lymphomaMTD determinationPrimary CNSSafety profile
2017
Phase I clinical trial on pomalidomide and dexamethasone in treating patients with relapsed/refractory primary central nervous system lymphoma (PCNSL) or primary vitreoretinal lymphoma (PVRL).
Tun H, Johnston P, Grommes C, Reeder C, Omuro A, Menke D, Copland J, DeAngelis L, Witzig T. Phase I clinical trial on pomalidomide and dexamethasone in treating patients with relapsed/refractory primary central nervous system lymphoma (PCNSL) or primary vitreoretinal lymphoma (PVRL). Journal Of Clinical Oncology 2017, 35: 7516-7516. DOI: 10.1200/jco.2017.35.15_suppl.7516.Peer-Reviewed Original ResearchPrimary central nervous system lymphomaOverall response rateRefractory primary central nervous system lymphomaPhase I clinical trialPrimary vitreoretinal lymphomaMTD cohortStable diseaseClinical trialsCentral nervous system lymphomaTherapeutic activityDiffuse large B-cell lymphomaLarge B-cell lymphomaDose level 3Grade 3/4 toxicitiesNovel immunomodulatory agentsNervous system lymphomaCycles of treatmentDose escalation levelsCSF/blood ratioB-cell lymphomaExcellent CNS penetrationPO weeklyPomalidomide treatmentPseudo progressionCNS lymphoma