2023
A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better
Djureinovic D, Weiss S, Krykbaeva I, Qu R, Vathiotis I, Moutafi M, Zhang L, Perdigoto A, Wei W, Anderson G, Damsky W, Hurwitz M, Johnson B, Schoenfeld D, Mahajan A, Hsu F, Miller-Jensen K, Kluger Y, Sznol M, Kaech S, Bosenberg M, Jilaveanu L, Kluger H. A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better. Molecular Cancer 2023, 22: 182. PMID: 37964379, PMCID: PMC10644655, DOI: 10.1186/s12943-023-01884-x.Peer-Reviewed Original ResearchConceptsStable diseasePartial responseMacrophage populationsThree-drug regimenUnconfirmed partial responsePhase I trialLimited treatment optionsMonocyte/macrophage populationNon-classical monocytesMurine melanoma modelTreatment-related changesResultsThirteen patientsWorse survivalI trialInflammatory tumorPatient populationTreatment optionsImmune cellsDisease progressionMurine studiesPreclinical modelsResistant melanomaAntigen presentationMurine modelCyTOF analysis
2021
A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1
Weiss SA, Djureinovic D, Jessel S, Krykbaeva I, Zhang L, Jilaveanu L, Ralabate A, Johnson B, Levit NS, Anderson G, Zelterman D, Wei W, Mahajan A, Trifan O, Bosenberg M, Kaech SM, Perry CJ, Damsky W, Gettinger S, Sznol M, Hurwitz M, Kluger HM. A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1. Clinical Cancer Research 2021, 27: 4757-4767. PMID: 34140403, PMCID: PMC9236708, DOI: 10.1158/1078-0432.ccr-21-0903.Peer-Reviewed Original ResearchConceptsAnti-PD-1/PD-L1Non-small cell lung cancerCell lung cancerRenal cell carcinomaPD-L1Lung cancerDisease progressionCommon treatment-related adverse eventsPD-1/PD-L1 inhibitorsTreatment-related adverse eventsPhase 2 doseSubstantial clinical challengeUnconfirmed partial responseDose-limiting toxicityPD-L1 inhibitorsPhase I trialDose-escalation designPro-inflammatory cytokinesMultiple tumor typesAsymptomatic elevationStable diseaseIntolerable toxicityAdverse eventsMedian durationPartial response
2018
First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study
Sullivan RJ, Infante JR, Janku F, Wong DJL, Sosman JA, Keedy V, Patel MR, Shapiro GI, Mier JW, Tolcher AW, Wang-Gillam A, Sznol M, Flaherty K, Buchbinder E, Carvajal RD, Varghese AM, Lacouture ME, Ribas A, Patel SP, DeCrescenzo GA, Emery CM, Groover AL, Saha S, Varterasian M, Welsch DJ, Hyman DM, Li BT. First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study. Cancer Discovery 2018, 8: 184-195. PMID: 29247021, DOI: 10.1158/2159-8290.cd-17-1119.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAminopyridinesFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesMutationNeoplasm StagingNeoplasmsProtein Kinase InhibitorsPyrrolesTomography, X-Ray ComputedTreatment OutcomeYoung AdultConceptsCommon treatment-related adverse eventsSolid tumorsHuman dose-escalation studyMulticenter phase I trialTreatment-related adverse eventsDose-escalation cohortsDose-expansion cohortsMutant solid tumorsPhase II doseAcceptable safety profileAdvanced solid tumorsDose-escalation studyPhase I trialPotent preclinical activityTreatment of patientsSolid tumor malignanciesERK1/2 kinase inhibitorEvaluable patientsDose expansionExpansion cohortAdverse eventsPartial responseDose escalationI trialSafety profile
2017
Phase Ib Study of Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Combination with Pembrolizumab (MK-3475) in Patients with Advanced Solid Tumors
Tolcher AW, Sznol M, Hu-Lieskovan S, Papadopoulos KP, Patnaik A, Rasco DW, Di Gravio D, Huang B, Gambhire D, Chen Y, Thall AD, Pathan N, Schmidt EV, Chow LQM. Phase Ib Study of Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Combination with Pembrolizumab (MK-3475) in Patients with Advanced Solid Tumors. Clinical Cancer Research 2017, 23: 5349-5357. PMID: 28634283, DOI: 10.1158/1078-0432.ccr-17-1243.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCombined Modality TherapyDiagnostic ImagingDrug MonitoringFemaleHumansImmunoglobulin GMaleMaximum Tolerated DoseMiddle AgedMolecular Targeted TherapyNeoplasm StagingNeoplasmsRetreatmentT-Lymphocyte SubsetsTreatment OutcomeTumor Necrosis Factor Receptor Superfamily, Member 9ConceptsAdvanced solid tumorsSolid tumorsTreatment-emergent adverse eventsPeripheral blood CD8Phase Ib studyTreatment-related discontinuationsDose-limiting toxicityCostimulatory receptor 4Event continual reassessment methodT cell costimulatory receptor 4Clin Cancer ResSupport further investigationBlood CD8Partial responseAdverse eventsDose escalationReceptor 4Clinical activityT cellsIb studyCombination treatmentContinual reassessment methodPatientsGrade 1Cancer Res
2014
Phase I/II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients With Advanced Melanoma
Ott PA, Hamid O, Pavlick AC, Kluger H, Kim KB, Boasberg PD, Simantov R, Crowley E, Green JA, Hawthorne T, Davis TA, Sznol M, Hwu P. Phase I/II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients With Advanced Melanoma. Journal Of Clinical Oncology 2014, 32: 3659-3666. PMID: 25267741, PMCID: PMC4879709, DOI: 10.1200/jco.2013.54.8115.Peer-Reviewed Original ResearchConceptsMaximum-tolerated doseObjective response rateGreater objective response rateGlembatumumab vedotinAdvanced melanomaGrade 3/4 treatment-related toxicitiesHuman immunoglobulin G2 monoclonal antibodyPhase I/II studyPhase II expansion cohortPromising objective response ratesEnd pointTreatment-related deathsPrimary end pointSecondary end pointsTreatment-related toxicityProgression-free survivalPhase II expansionMonomethyl auristatin E.Stable diseaseExpansion cohortII studyPartial responseDose escalationMore patientsFrequent dosing
2012
Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial
Margolin K, Ernstoff MS, Hamid O, Lawrence D, McDermott D, Puzanov I, Wolchok JD, Clark JI, Sznol M, Logan TF, Richards J, Michener T, Balogh A, Heller KN, Hodi FS. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. The Lancet Oncology 2012, 13: 459-465. PMID: 22456429, DOI: 10.1016/s1470-2045(12)70090-6.Peer-Reviewed Original ResearchConceptsBrain metastasesCohort ACohort BSerum aspartate aminotransferaseDisease controlIntravenous ipilimumabAdverse eventsAdvanced melanomaCohort B.Common grade 3 adverse eventsAspartate aminotransferaseGrade 3 adverse eventsCommon grade 3Drug-related complicationsPhase 2 trialProportion of patientsUnexpected toxic effectsBristol-Myers SquibbStable diseaseCorticosteroid treatmentPrimary endpointStable dosePartial responseWeek 24Complete response
2010
A phase 2 trial of dasatinib in advanced melanoma
Kluger HM, Dudek AZ, McCann C, Ritacco J, Southard N, Jilaveanu LB, Molinaro A, Sznol M. A phase 2 trial of dasatinib in advanced melanoma. Cancer 2010, 117: 2202-2208. PMID: 21523734, PMCID: PMC3116034, DOI: 10.1002/cncr.25766.Peer-Reviewed Original ResearchConceptsProgression-free survivalC-kit mutationsPhase 2 trialResponse ratePartial responseMedian progression-free survivalMelanoma cell proliferationDaily dasatinibMucosal primaryPFS ratesStarting dosageCommon toxicitiesUnresectable melanomaAdvanced melanomaPleural effusionMelanoma patientsPredictive biomarkersMinor responseCombination trialsTumor assessmentDose reductionPatientsPrespecified endpointsDasatinibMelanoma
2007
A Phase I study of the novel ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine®) in combination with the nucleoside analog fludarabine for patients with refractory acute leukemias and aggressive myeloproliferative disorders
Karp JE, Giles FJ, Gojo I, Morris L, Greer J, Johnson B, Thein M, Sznol M, Low J. A Phase I study of the novel ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine®) in combination with the nucleoside analog fludarabine for patients with refractory acute leukemias and aggressive myeloproliferative disorders. Leukemia Research 2007, 32: 71-77. PMID: 17640728, PMCID: PMC2726775, DOI: 10.1016/j.leukres.2007.05.003.Peer-Reviewed Original ResearchConceptsAggressive myeloproliferative disorderDaily x 5Refractory acute leukemiaMyeloproliferative disordersAcute leukemiaRibonucleotide reductase inhibitorReductase inhibitorsDays of fludarabineRefractory myeloid malignanciesPhase I trialDrug-related toxicityNovel ribonucleotide reductase inhibitorNucleoside analog fludarabinePotent ribonucleotide reductase inhibitorPartial responseI trialMetabolic acidosisSchedule AFludarabineMyeloid malignanciesPatientsPhase ILeukemiaDisordersInhibitors
2004
A phase I trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in combination with gemcitabine for patients with advanced cancer
Yen Y, Margolin K, Doroshow J, Fishman M, Johnson B, Clairmont C, Sullivan D, Sznol M. A phase I trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in combination with gemcitabine for patients with advanced cancer. Cancer Chemotherapy And Pharmacology 2004, 54: 331-342. PMID: 15148626, DOI: 10.1007/s00280-004-0821-2.Peer-Reviewed Original ResearchConceptsPhase I trialI trialAdvanced cancerToxicity profileDiffuse coronary artery diseaseST-T wave changesGemcitabine plasma concentrationsLarge liver metastasesNon-specific ST-T wave changesPhase II trialCoronary artery diseaseAsymptomatic myocardial infarctionMild QT prolongationCytotoxicity of gemcitabineEvaluable patientsGemcitabine 1000Gemcitabine doseAcute hypotensionII trialPartial responseArtery diseaseCardiovascular reserveComplete responseLiver metastasesAcute symptoms