2020
Mogamulizumab in Combination with Durvalumab or Tremelimumab in Patients with Advanced Solid Tumors: A Phase I Study
Zamarin D, Hamid O, Nayak-Kapoor A, Sahebjam S, Sznol M, Collaku A, Fox FE, Marshall MA, Hong DS. Mogamulizumab in Combination with Durvalumab or Tremelimumab in Patients with Advanced Solid Tumors: A Phase I Study. Clinical Cancer Research 2020, 26: 4531-4541. PMID: 32586937, PMCID: PMC8375360, DOI: 10.1158/1078-0432.ccr-20-0328.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsDose-Response Relationship, DrugFemaleHumansLymphocyte DepletionMaleMiddle AgedNeoplasm StagingPancreatic NeoplasmsReceptors, CCR4T-Lymphocytes, RegulatoryYoung AdultConceptsAdvanced solid tumorsDose escalationSolid tumorsCohort expansionEffector regulatory T cellsC chemokine receptor 4Phase IDose-expansion cohortsAdvanced pancreatic cancerObjective response rateMajority of patientsRegulatory T cellsChemokine receptor 4Potent antitumor efficacyMogamulizumab treatmentCheckpoint inhibitorsDose expansionExpansion cohortIntratumoral TregsPrimary endpointClinical responseEscalation studyBaseline degreePharmacodynamic profilePancreatic cancer
2016
Phase I trial of daily triapine in combination with cisplatin chemotherapy for advanced-stage malignancies
Kunos CA, Chu E, Beumer JH, Sznol M, Ivy SP. Phase I trial of daily triapine in combination with cisplatin chemotherapy for advanced-stage malignancies. Cancer Chemotherapy And Pharmacology 2016, 79: 201-207. PMID: 27878356, PMCID: PMC5226891, DOI: 10.1007/s00280-016-3200-x.Peer-Reviewed Original ResearchConceptsPhase I trialSolid tumor malignanciesI trialObjective responseTumor malignancyDaily days 1Frequent grade 3Advanced-stage malignanciesDose-finding phase I trialResultsThe MTDStable diseasePrimary endpointSecondary endpointsVulvar cancerElectrolyte abnormalitiesAdverse eventsCisplatin chemotherapyUterine cervixGrade 3Day 1Day 2Day 3PatientsMalignancyDifferent schedulesPembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial
Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, Tsiouris AJ, Cohen J, Vortmeyer A, Jilaveanu L, Yu J, Hegde U, Speaker S, Madura M, Ralabate A, Rivera A, Rowen E, Gerrish H, Yao X, Chiang V, Kluger HM. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. The Lancet Oncology 2016, 17: 976-983. PMID: 27267608, PMCID: PMC5526047, DOI: 10.1016/s1470-2045(16)30053-5.Peer-Reviewed Original ResearchConceptsProgressive brain metastasesUntreated brain metastasesBrain metastasis responseYale Cancer CenterBrain metastasesPhase 2 trialCell lung cancerAdverse eventsMetastasis responseCancer CenterLung cancerMelanoma cohortGrade 3 colitisGrade 3 fatigueGrade 3 pneumonitisPD-1 axisAcute kidney injuryNeurological adverse eventsPD-1 inhibitorsAcceptable safety profilePD-L1 expressionSystemic immunotherapyKidney injuryPrimary endpointNSCLC cohort
2015
Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial
Weber JS, D'Angelo SP, Minor D, Hodi FS, Gutzmer R, Neyns B, Hoeller C, Khushalani NI, Miller WH, Lao CD, Linette GP, Thomas L, Lorigan P, Grossmann KF, Hassel JC, Maio M, Sznol M, Ascierto PA, Mohr P, Chmielowski B, Bryce A, Svane IM, Grob JJ, Krackhardt AM, Horak C, Lambert A, Yang AS, Larkin J. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. The Lancet Oncology 2015, 16: 375-384. PMID: 25795410, DOI: 10.1016/s1470-2045(15)70076-8.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCTLA-4 AntigenDisease-Free SurvivalDrug-Related Side Effects and Adverse ReactionsFemaleHumansIpilimumabMaleMelanomaMiddle AgedNeoplasm StagingNivolumabPaclitaxelProto-Oncogene Proteins B-rafConceptsPhase 3 trialObjective responseAdvanced melanomaBRAF inhibitorsPrimary endpointAdverse eventsGrade 3Human IgG4 PD-1 immune checkpoint inhibitor antibodyDrug-related serious adverse eventsICC groupImmune checkpoint inhibitor antibodyCheckpoint inhibitor antibodyDurable objective responsesLater-line treatmentNivolumab-treated patientsSafety of nivolumabTreatment-related deathsUnacceptable toxic effectsSerious adverse eventsProportion of patientsFirst interim analysisNew treatment optionsBest overall responseDose of treatmentHigh unmet need
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