2024
A Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2-Altered Advanced Solid Tumor Malignancies (NCI 10170)
Maldonado E, Rathmell W, Shapiro G, Takebe N, Rodon J, Mahalingam D, Trikalinos N, Kalebasty A, Parikh M, Boerner S, Balido C, Krings G, Burns T, Bergsland E, Munster P, Ashworth A, LoRusso P, Aggarwal R. A Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2-Altered Advanced Solid Tumor Malignancies (NCI 10170). Cancer Research Communications 2024, 4: 1793-1801. PMID: 38920407, PMCID: PMC11264598, DOI: 10.1158/2767-9764.crc-24-0213.Peer-Reviewed Original ResearchSolid tumor malignanciesStable diseaseTumor malignancyAdverse eventsDepth of tumor responseLoss of H3K36me3Median duration of treatmentAdvanced solid tumor malignanciesClear cell renal cell carcinomaMinor tumor regressionsProlonged stable diseaseArchival tumor tissuePhase II studyCell renal cell carcinomaPhase II trialRenal cell carcinomaDuration of treatmentArchival tissue samplesSimon's two-stageTumor responseTumor regressionII trialMedian durationII studySETD2 mutationsSafety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of KT-253, a targeted protein degrader of MDM2, in patients with relapsed/refractory (R/R) solid tumors, lymphoma, high grade myeloid malignancies and acute lymphoblastic leukemia (ALL).
Khawaja M, Naqash A, Schneider R, Shastri A, Stahl M, Moser J, Abdel Karim N, Madanat Y, Jonas B, Stein E, Gadgeel S, McCloskey J, Gollerkeri A, Perea R, Chutake Y, Agarwal S, Henrick P, Shi K, Daver N. Safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of KT-253, a targeted protein degrader of MDM2, in patients with relapsed/refractory (R/R) solid tumors, lymphoma, high grade myeloid malignancies and acute lymphoblastic leukemia (ALL). Journal Of Clinical Oncology 2024, 42: 3084-3084. DOI: 10.1200/jco.2024.42.16_suppl.3084.Peer-Reviewed Original ResearchAcute lymphoblastic leukemiaMouse double minute 2Arm BArm AAdverse eventsSolid tumorsOpen-label phase 1 studyMouse double minute 2 inhibitorUpregulated p53 activityDecreased oral intakeMerkel cell carcinomaAdenoid cystic carcinomaPhase 1 studySolid tumor typesAcute apoptotic responseDose-dependent increaseGDF-15 proteinPreclinical PDX modelsWild-type p53Anti-tumor activityDouble minute 2Upregulation of CDKN1AR/R AMLDose escalationTumor regressionASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts.
Hu B, Wiesehöfer M, de Miguel F, Liu Z, Chan L, Choi J, Melnick M, Arnal Estape A, Walther Z, Zhao D, Lopez-Giraldez F, Wurtz A, Cai G, Fan R, Gettinger S, Xiao A, Yan Q, Homer R, Nguyen D, Politi K. ASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts. Cancer Research 2024, 84: 1303-1319. PMID: 38359163, DOI: 10.1158/0008-5472.can-23-0438.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsPatient-derived xenograftsEGFR mutant lung cancerMutant lung cancerPre-treatment tumorsResidual diseaseDrug toleranceLung cancerResidual tumor cells in vivoEGFR mutant lung adenocarcinomaTyrosine kinase inhibitor osimertinibEGFR tyrosine kinase inhibitorsTyrosine kinase inhibitor treatmentTumor cells in vivoMutant lung adenocarcinomaMaximal tumor regressionTranscription factor Ascl1Drug-tolerant cellsTime of maximal responseEvidence of cellsCells in vivoOsimertinib treatmentTumor regressionSingle cell transcriptional profilingTumor cells
2023
Molecular Mechanism of Fasting-Mimicking Diet in Inhibiting Colorectal Cancer Progression: Implications for Immune Therapy and Metabolic Regulation.
Bush C, Perry R. Molecular Mechanism of Fasting-Mimicking Diet in Inhibiting Colorectal Cancer Progression: Implications for Immune Therapy and Metabolic Regulation. Cancer Research 2023, 83: 3493-3494. PMID: 37908187, DOI: 10.1158/0008-5472.can-23-2257.Commentaries, Editorials and LettersConceptsFasting-mimicking dietColorectal cancer progressionIgA class switchingColorectal cancerCancer progressionB cellsClass switchingFatty acid oxidationAnticancer immunityAntitumor immunityImmune therapyMolecular mechanismsTumor regressionMouse modelCaloric restrictionAnticancer effectsMetabolic reprogrammingProgressionDietCancerAcid oxidationCancer researchImmunityMetabolic regulationCellsIntrathecal delivery of nanoparticle PARP inhibitor to the cerebrospinal fluid for the treatment of metastatic medulloblastoma
Khang M, Lee J, Lee T, Suh H, Lee S, Cavaliere A, Rushing A, Geraldo L, Belitzky E, Rossano S, de Feyter H, Shin K, Huttner A, Roussel M, Thomas J, Carson R, Marquez-Nostra B, Bindra R, Saltzman W. Intrathecal delivery of nanoparticle PARP inhibitor to the cerebrospinal fluid for the treatment of metastatic medulloblastoma. Science Translational Medicine 2023, 15: eadi1617. PMID: 37910601, PMCID: PMC11078331, DOI: 10.1126/scitranslmed.adi1617.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidDelivery of drugsEffective therapyTherapeutic indexPARP inhibitorsBlood-brain barrierSite of tumorRapid systemic clearanceXenograft mouse modelSolvent evaporation processAdministration of substancesLeptomeningeal spreadIntrathecal deliveryLeptomeningeal metastasesBrain penetrationSystemic clearanceTumor regressionPolymer nanoparticlesMetastatic medulloblastomaMouse modelPediatric medulloblastomaDrug accumulationCSF turnoverEncapsulated drugsPET imagingCombinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance.
Krykbaeva I, Bridges K, Damsky W, Pizzurro G, Alexander A, McGeary M, Park K, Muthusamy V, Eyles J, Luheshi N, Turner N, Weiss S, Olino K, Kaech S, Kluger H, Miller-Jensen K, Bosenberg M. Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance. Cancer Immunology Research 2023, 11: 1332-1350. PMID: 37478171, DOI: 10.1158/2326-6066.cir-22-0699.Peer-Reviewed Original ResearchConceptsPD-1 resistanceDendritic cellsTumor regressionAnti-PD-1 resistanceActivates Dendritic CellsCytokine secretion profilingSystemic cytokine profileTriple therapy combinationInnate immune activationAdaptive immune responsesComplete tumor regressionMajority of miceSignificant clinical challengeMouse melanoma modelT cell activationAgonistic CD40Checkpoint inhibitorsDC subsetsTriple therapyCytokine profileImmune activationCombinatorial immunotherapyTherapy combinationsT cellsClinical challengeA phase 2 study of the WEE1 inhibitor AZD1775 in SETD2-deficient advanced solid tumor malignancies.
Maldonado E, Rathmell W, Shapiro G, Rodon Ahnert J, Mahalingam D, Trikalinos N, Rezazadeh A, Adorno Febles V, Parikh M, Boerner S, Krings G, Takebe N, LoRusso P, Aggarwal R. A phase 2 study of the WEE1 inhibitor AZD1775 in SETD2-deficient advanced solid tumor malignancies. Journal Of Clinical Oncology 2023, 41: 3104-3104. DOI: 10.1200/jco.2023.41.16_suppl.3104.Peer-Reviewed Original ResearchClear cell renal cell carcinomaSolid tumor malignanciesClinical benefit rateObjective response rateDuration of responseTumor malignancyEvaluable ptsStable diseaseObjective responseAdverse eventsTumor regressionMetastatic clear cell renal cell carcinomaAdvanced solid tumor malignanciesMetastatic solid tumor malignanciesCommon adverse eventsDurable stable diseaseECOG PS 0RECIST 1.1 criteriaSubset of ptsPhase 2 studyCohort of patientsCell renal cell carcinomaNext-generation sequencing panelBest overall responseRenal cell carcinomaSurvival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab
Topalian S, Sznol M, McDermott D, Kluger H, Carvajal R, Sharfman W, Brahmer J, Lawrence D, Atkins M, Powderly J, Leming P, Lipson E, Puzanov I, Smith D, Taube J, Wigginton J, Kollia G, Gupta A, Pardoll D, Sosman J, Hodi F. Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab. Journal Of Clinical Oncology 2023, 41: 943-954. PMID: 36750016, DOI: 10.1200/jco.22.02272.Peer-Reviewed Original ResearchLong-term safetyOverall survivalToxicity ratesTumor regressionResponse durationOngoing randomized clinical trialsDurable tumor remissionNivolumab-treated patientsMedian overall survivalMedian response durationPD-1 blockadeObjective tumor regressionMaintenance of responseCell death 1Randomized clinical trialsSimilar patient populationsActivated T cellsDrug discontinuationIntravenous nivolumabNivolumab therapyNivolumab treatmentTreatment discontinuationObjective responseAdvanced melanomaDeath-1
2022
YES1 Is a Druggable Oncogenic Target in SCLC
Redin E, Garrido-Martin EM, Valencia K, Redrado M, Solorzano JL, Carias R, Echepare M, Exposito F, Serrano D, Ferrer I, Nunez-Buiza A, Garmendia I, García-Pedrero JM, Gurpide A, Paz-Ares L, Politi K, Montuenga LM, Calvo A. YES1 Is a Druggable Oncogenic Target in SCLC. Journal Of Thoracic Oncology 2022, 17: 1387-1403. PMID: 35988891, DOI: 10.1016/j.jtho.2022.08.002.Peer-Reviewed Original ResearchConceptsSubpopulation of patientsOncogenic targetsPatient-derived xenograftsMarked antitumor activityGain/amplificationPlasma-derived exosomesDistant metastasisIndependent predictorsTargetable oncogenesPoor prognosisAggressive subtypeClinical managementLung cancerPharmacologic blockadeTumor regressionMouse modelTumor growthPlasma exosomesMolecular subgroupsPharmacologic inhibitionMetastasisAntitumor activityFunctional experimentsOrganoid modelsClinical samplesPhase II Study of Enzalutamide for Patients With Androgen Receptor–Positive Salivary Gland Cancers (Alliance A091404)
Ho AL, Foster NR, Zoroufy AJ, Campbell JD, Worden F, Price K, Adkins D, Bowles DW, Kang H, Burtness B, Sherman E, Morton R, Morris LGT, Nadeem Z, Katabi N, Munster P, Schwartz GK. Phase II Study of Enzalutamide for Patients With Androgen Receptor–Positive Salivary Gland Cancers (Alliance A091404). Journal Of Clinical Oncology 2022, 40: 4240-4249. PMID: 35867947, PMCID: PMC9916043, DOI: 10.1200/jco.22.00229.Peer-Reviewed Original ResearchConceptsSalivary gland cancerPrimary end pointProgression-free survivalAndrogen receptorStable diseaseEnd pointOverall survivalPartial responseGland cancerTumor regressionPartial response/stable diseaseBest overall response rateMedian progression-free survivalResponse/stable diseaseHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Common adverse eventsMedian overall survivalPhase II studySecondary end pointsPhase II trialFree testosterone levelsGrowth factor receptor 2Overall response rateProgression of diseaseActivity 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-lifeTumor MHC Class I Expression Associates with Intralesional IL2 Response in Melanoma
Pourmaleki M, Jones C, Ariyan C, Zeng Z, Pirun M, Navarrete D, Li Y, Zhang M, Nandakumar S, Campos C, Nadeem S, Klimstra D, Temple-Oberle C, Brenn T, Lipson E, Schenk K, Stein J, Taube J, White M, Traweek R, Wargo J, Kirkwood J, Gasmi B, Goff S, Corwin A, McDonough E, Ginty F, Callahan M, Schietinger A, Socci N, Mellinghoff I, Hollmann T. Tumor MHC Class I Expression Associates with Intralesional IL2 Response in Melanoma. Cancer Immunology Research 2022, 10: 303-313. PMID: 35013003, PMCID: PMC8898286, DOI: 10.1158/2326-6066.cir-21-1083.Peer-Reviewed Original ResearchConceptsCD8+ T cellsT cellsUntreated lesionsTumor cellsCohort of metastatic melanoma patientsProliferating CD8+ T cellsPredictive biomarkers of treatment responseExpression of PD-1MHC class I expressionBiomarkers of treatment responseMetastatic melanoma patientsB cell aggregatesResponse to IL2Class I expressionExpression of IFNGIL2 therapyPD-1Cancer immunotherapyTumor regressionMelanoma patientsLAG-3Tim-3IL2 responsivenessInjected lesionsPredictive biomarkersPraluzatamab Ravtansine, a CD166-Targeting Antibody–Drug Conjugate, in Patients with Advanced Solid Tumors: An Open-Label Phase I/II Trial
Boni V, Fidler MJ, Arkenau HT, Spira A, Meric-Bernstam F, Uboha N, Sanborn RE, Sweis RF, LoRusso P, Nagasaka M, Garcia-Corbacho J, Jalal S, Harding JJ, Kim SK, Miedema IHC, Vugts DJ, Huisman MC, Zwezerijnen GJC, van Dongen GAMS, van Oordt C, Wang S, Dang T, Zein IA, Vasiljeva O, Lyman SK, Paton V, Hannah A, Liu JF. Praluzatamab Ravtansine, a CD166-Targeting Antibody–Drug Conjugate, in Patients with Advanced Solid Tumors: An Open-Label Phase I/II Trial. Clinical Cancer Research 2022, 28: 2020-2029. PMID: 35165101, PMCID: PMC9365353, DOI: 10.1158/1078-0432.ccr-21-3656.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsOpen-label phase I/II trialSolid tumorsPhase I/II trialPhase I/II clinical trialsBasis of tolerabilityPhase II doseBreast cancer subsetsAntibody-drug conjugatesProtease-cleavable linkerEligible patientsPosttreatment biopsiesPrior therapyStable diseaseII trialPartial responseSafety profileTumor regressionClinical trialsPrevalent subtypeCancer subsetsClinical activityMetastatic cancerBreast cancerMedian number
2021
Phase 1/2 study of intratumoral G100 (TLR4 agonist) with or without pembrolizumab in follicular lymphoma
Halwani AS, Panizo C, Isufi I, Herrera AF, Okada CY, Cull EH, Kis B, Chaves JM, Bartlett NL, Ai W, de la Cruz-Merino L, Bryan LJ, Houot R, Linton K, Briones J, Chau I, von Keudell GR, Lu H, Yakovich A, Chen M, JH T, Yurasov S, Hsu FJ, Flowers CR. Phase 1/2 study of intratumoral G100 (TLR4 agonist) with or without pembrolizumab in follicular lymphoma. Leukemia & Lymphoma 2021, 63: 821-833. PMID: 34865586, DOI: 10.1080/10428194.2021.2010057.Peer-Reviewed Original ResearchConceptsFollicular lymphomaTumor regressionAnti-tumor immune responseToll-like receptor 4 agonistAbscopal tumor regressionAdverse events gradeImmune-mediated responsePhase 1/2 trialOverall response rateEarly phase studiesLow-dose radiationDose expansionDose escalationPreliminary efficacyTLR4 agonistImmune responseUnexpected toxicitiesEvents gradeIntratumoral injectionResponse ratePatientsLymphomaPembrolizumabAgonistsInjectionWEE1 inhibition induces anti-tumor immunity by activating ERV and the dsRNA pathway
Guo E, Xiao R, Wu Y, Lu F, Liu C, Yang B, Li X, Fu Y, Wang Z, Li Y, Huang Y, Li F, Wu X, You L, Qin T, Lu Y, Huang X, Ma D, Mills G, Sun C, Chen G. WEE1 inhibition induces anti-tumor immunity by activating ERV and the dsRNA pathway. Journal Of Experimental Medicine 2021, 219: e20210789. PMID: 34825915, PMCID: PMC8628262, DOI: 10.1084/jem.20210789.Peer-Reviewed Original ResearchMeSH KeywordsA549 CellsAnimalsAntineoplastic Combined Chemotherapy ProtocolsCD8-Positive T-LymphocytesCell Cycle ProteinsCell Line, TumorEndogenous RetrovirusesEnzyme InhibitorsFemaleGene Expression Regulation, NeoplasticHCT116 CellsHumansImmune Checkpoint InhibitorsMice, Inbred BALB CMice, Inbred C57BLMice, Inbred NODMice, SCIDNeoplasms, ExperimentalProtein-Tyrosine KinasesPyrazolesPyrimidinonesRNA, Double-StrandedSignal TransductionTumor BurdenConceptsImmune checkpoint blockadeAnti-tumor immunityEndogenous retroviral elementsWEE1 inhibitionCheckpoint blockadeCD8+ T cell-dependent mannerSensitivity to immune checkpoint blockadeResponse to immune checkpoint blockadeAnti-tumor T cellsCombination of WEE1 inhibitorT cell-dependent mannerPathway-targeted therapiesMultiple tumor modelsPopulation of patientsEmergence of resistanceDown-regulating FoxM1Viral defense pathwaysPD-L1Tumor regressionCombination therapyTargeted therapyCombination partnerT cellsPatient selectionWEE1 inhibitorElevated murine HB-EGF confers sensitivity to diphtheria toxin in EGFR-mutant lung adenocarcinoma
Robles-Oteiza C, Ayeni D, Levy S, Homer RJ, Kaech SM, Politi K. Elevated murine HB-EGF confers sensitivity to diphtheria toxin in EGFR-mutant lung adenocarcinoma. Disease Models & Mechanisms 2021, 14: dmm049072. PMID: 34494649, PMCID: PMC8617309, DOI: 10.1242/dmm.049072.Peer-Reviewed Original ResearchConceptsHuman diphtheria toxin receptorDiphtheria toxin receptorTumor regressionEGFR-mutant lung cancerEGFR-mutant lung adenocarcinomaEGFR-mutant tumorsMutant EGFRTissue-specific promotorsFVB miceLung cancerSystemic administrationLung adenocarcinomaMurine lungRapid regressionConditional ablationTumor cellsUpregulated expressionMiceElevated expressionToxin receptorHB-EGFCell populationsHBEGFEGFRPrimary targetImmune Therapy: What Can We Learn From Acquired Resistance?
Grant M, Politi K, Gettinger S. Immune Therapy: What Can We Learn From Acquired Resistance? Current Cancer Research 2021, 75-114. DOI: 10.1007/978-3-030-74028-3_5.ChaptersNon-small cell lung cancerAdvanced non-small cell lung cancerDeath-1 pathway inhibitorsPD-1 axis inhibitorsInitial tumor regressionCell lung cancerImmune checkpoint pathwaysIFN-γ signalingMediators of resistanceDisease stabilitySystemic progressionMost patientsLocal therapyClinical criteriaLung cancerTumor regressionTumor typesDisease sitesPathway inhibitorAcquired ResistancePresentation defectPatientsTranslational workProgressionEpigenetic changesYAP1 Withdrawal in Hepatoblastoma Drives Therapeutic Differentiation of Tumor Cells to Functional Hepatocyte‐Like Cells
Smith J, Rodríguez T, Mou H, Kwan S, Pratt H, Zhang X, Cao Y, Liang S, Ozata D, Yu T, Yin Q, Hazeltine M, Weng Z, Sontheimer E, Xue W. YAP1 Withdrawal in Hepatoblastoma Drives Therapeutic Differentiation of Tumor Cells to Functional Hepatocyte‐Like Cells. Hepatology 2021, 73: 1011-1027. PMID: 32452550, PMCID: PMC8500588, DOI: 10.1002/hep.31389.Peer-Reviewed Original ResearchConceptsYes-associated protein 1Tumor cellsTumor regressionB-cateninStage IV hepatoblastomaResidual tumor cellsPediatric liver tumorsTherapeutic targetLong-term regressionTherapeutic differentiationHepatocyte-like morphologyFunctional hepatocyte-like cellsChildren's HbHB tumorsHepatocyte gene expressionHepatocyte-like cellsTranscription factor occupancyChemotherapeutic advancesTargeted therapyTumor landscapeLiver tumorsMurine modelHepatoblastomaTumorPromote cell death
2019
Small-Molecule Dual PLK1 and BRD4 Inhibitors are Active Against Preclinical Models of Pediatric Solid Tumors
Timme N, Han Y, Liu S, Yosief H, García H, Bei Y, Klironomos F, MacArthur I, Szymansky A, von Stebut J, Bardinet V, Dohna C, Künkele A, Rolff J, Hundsdörfer P, Lissat A, Seifert G, Eggert A, Schulte J, Zhang W, Henssen A. Small-Molecule Dual PLK1 and BRD4 Inhibitors are Active Against Preclinical Models of Pediatric Solid Tumors. Translational Oncology 2019, 13: 221-232. PMID: 31869746, PMCID: PMC6931204, DOI: 10.1016/j.tranon.2019.09.013.Peer-Reviewed Original ResearchPediatric tumor cell linesTumor cell linesTreatment of patient-derived xenograftsClinical response to therapySignificant tumor regressionPediatric solid tumorsResponse to therapyPatient-derived xenograftsPediatric cancer modelsTumor-specific activationCell linesRhabdomyosarcoma tumor cellsTumor regressionPreclinical modelsSolid tumorsAntitumor effectCancer modelsTumor cellsConcurrent inhibitionAntitumor activityInduce apoptosisSimultaneous inhibitionMolecular targetsBRD4 inhibitorsCentral regulatorATIM-17. A PHASE I TRIAL OF HYPOFRACTIONATED STEREOTACTIC IRRADIATION (HFSRT) COMBINED WITH NIVOLUMAB (NIVO), IPILIMUMAB (IPI) AND BEVACIZUMAB (BEV) IN PATIENTS (PTS) WITH RECURRENT HIGH GRADE GLIOMAS
Sahebjam S, Forsyth P, Tran N, Etame A, Arrington J, Jaglal M, Mokhtari S, MacAulay R, Wicklund M, Evernden B, Gatewood T, Robinson T, Raval R, Yu M. ATIM-17. A PHASE I TRIAL OF HYPOFRACTIONATED STEREOTACTIC IRRADIATION (HFSRT) COMBINED WITH NIVOLUMAB (NIVO), IPILIMUMAB (IPI) AND BEVACIZUMAB (BEV) IN PATIENTS (PTS) WITH RECURRENT HIGH GRADE GLIOMAS. Neuro-Oncology 2019, 21: vi5-vi5. PMCID: PMC6847102, DOI: 10.1093/neuonc/noz175.017.Peer-Reviewed Original ResearchGrade 1 elevationExpansion cohortSafety cohortPD-1/PDLStrong pre-clinical evidencesAnti-tumor immune responseRecurrent high-grade gliomaPhase IDose-expansion cohortsGrade 1 anorexiaGrade 1 diarrheaRT treatment fieldUse of corticosteroidsPre-clinical evidenceHigh-grade gliomasPrimary study objectiveCommon toxicitiesEligible ptsPrior RTSecondary endpointsFlat doseRecurrent tumorsGrade IIITumor regressionEfficacy data
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