2021
Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma: Evaluation of impact of prior anti-PD-1 therapy.
Larkin J, Sarnaik A, Chesney J, Khushalani N, Kirkwood J, Weber J, Lewis K, Medina T, Kluger H, Thomas S, Domingo-Musibay E, Olah J, Whitman E, Martin-Algarra S, Corrie P, Lutzky J, Shi W, Wu R, Fardis M, Hamid O. Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma: Evaluation of impact of prior anti-PD-1 therapy. Journal Of Clinical Oncology 2021, 39: 9505-9505. DOI: 10.1200/jco.2021.39.15_suppl.9505.Peer-Reviewed Original ResearchAnti-PD-1 therapyPrior anti-PD-1 therapyObjective response rateImmune checkpoint inhibitorsAdvanced melanomaPrimary resistanceAnti-PD-1 resistanceAnti-PD-1 responseBaseline tumor burdenDays of cyclophosphamideDays of fludarabineMedian cumulative durationMedian prior linesLong-term followAdoptive cell therapyStandard of careDetection of progressionNew safety risksDuration of exposureAutologous tumorMelanoma progressPrior therapyRECIST 1.1TIL productionCheckpoint inhibitorsLifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma
Sarnaik AA, Hamid O, Khushalani NI, Lewis KD, Medina T, Kluger HM, Thomas SS, Domingo-Musibay E, Pavlick AC, Whitman ED, Martin-Algarra S, Corrie P, Curti BD, Oláh J, Lutzky J, Weber JS, Larkin JMG, Shi W, Takamura T, Jagasia M, Qin H, Wu X, Chartier C, Finckenstein F, Fardis M, Kirkwood JM, Chesney JA. Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma. Journal Of Clinical Oncology 2021, 39: 2656-2666. PMID: 33979178, PMCID: PMC8376325, DOI: 10.1200/jco.21.00612.Peer-Reviewed Original ResearchConceptsObjective response rateDisease control rateAdvanced melanomaPrimary refractoryControl rateMetastatic melanomaTreatment optionsInterleukin-2Investigator-assessed objective response rateHigh-dose interleukin-2Tumor-Infiltrating Lymphocyte TherapyImmune checkpoint inhibitorsPrimary end pointTumor-infiltrating lymphocytesEffective treatment optionLimited treatment optionsAdoptive cell therapyMajor unmet needLymphodepletion regimenPrior therapyCheckpoint inhibitorsAdverse eventsDurable responsesMedian durationPartial response
2020
Long-term follow up of lifileucel (LN-144) cryopreserved autologous tumor infiltrating lymphocyte therapy in patients with advanced melanoma progressed on multiple prior therapies.
Sarnaik A, Khushalani N, Chesney J, Lewis K, Medina T, Kluger H, Thomas S, Domingo Musibay E, Pavlick A, Whitman E, Martin-Algarra S, Corrie P, Lutzky J, Hamid O, Wu R, Shi W, Fardis M, Weber J, Larkin J, Kirkwood J. Long-term follow up of lifileucel (LN-144) cryopreserved autologous tumor infiltrating lymphocyte therapy in patients with advanced melanoma progressed on multiple prior therapies. Journal Of Clinical Oncology 2020, 38: 10006-10006. DOI: 10.1200/jco.2020.38.15_suppl.10006.Peer-Reviewed Original ResearchBRAF/MEK inhibitorsMultiple prior therapiesMedian DoRPrior therapyCheckpoint inhibitorsAdvanced melanomaMelanoma patientsMedian studyMEK inhibitorsBaseline tumor burdenCohort 2 patientsIL-2 regimensAdverse event profileLong-term followMetastatic melanoma patientsIL-2 dosesAdoptive cell therapyUnresectable metastatic melanomaBaseline disease burdenBody's natural defensesAnti-cancer therapyAutologous tumorRECIST v1.1TIL productionAdvanced disease
2019
Safety and efficacy of cryopreserved autologous tumor infiltrating lymphocyte therapy (LN-144, lifileucel) in advanced metastatic melanoma patients who progressed on multiple prior therapies including anti-PD-1.
Sarnaik A, Khushalani N, Chesney J, Kluger H, Curti B, Lewis K, Thomas S, Whitman E, Hamid O, Lutzky J, Pavlick A, Weber J, Larkin J, Barton D, Yung L, Suzuki S, Fardis M, Kirkwood J. Safety and efficacy of cryopreserved autologous tumor infiltrating lymphocyte therapy (LN-144, lifileucel) in advanced metastatic melanoma patients who progressed on multiple prior therapies including anti-PD-1. Journal Of Clinical Oncology 2019, 37: 2518-2518. DOI: 10.1200/jco.2019.37.15_suppl.2518.Peer-Reviewed Original ResearchBRAF/MEK inhibitorsTumor-infiltrating lymphocytesMetastatic melanoma patientsMelanoma patientsTIL therapyPrior therapyAdvanced metastatic melanoma patientsDurable long-term responsesMEK inhibitorsBaseline tumor burdenCohort 2 patientsMultiple prior therapiesTIL infusion productsIL-2 dosesAdoptive cell therapyUnresectable metastatic melanomaBaseline disease burdenOverall disease controlAutologous tumorTIL infusionTIL productionMedian followCheckpoint inhibitorsUnresectable melanomaAdverse eventsSafety and efficacy of cryopreserved autologous tumor infiltrating lymphocyte therapy (LN-144, lifileucel) in advanced metastatic melanoma patients previously treated with at least one prior systemic therapy.
Sarnaik A, Thomas S, Davar D, Kirkwood J, Kluger H, Lutzky J, Wilson M, Pavlick A, Curti B, Whitman E, Phan G, Ernstoff M, Takamura K, Barton D, Suzuki S, Karyampudi L, Samberg N, Fardis M, Chesney J. Safety and efficacy of cryopreserved autologous tumor infiltrating lymphocyte therapy (LN-144, lifileucel) in advanced metastatic melanoma patients previously treated with at least one prior systemic therapy. Journal Of Clinical Oncology 2019, 37: 136-136. DOI: 10.1200/jco.2019.37.8_suppl.136.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesBRAF/MEK inhibitorsMetastatic melanoma patientsMetastatic melanomaPrior therapyCheckpoint inhibitorsMelanoma patientsIL-2Advanced metastatic melanoma patientsHigh-dose IL-2MEK inhibitorsBaseline tumor burdenCohort 2 patientsDose IL-2Frequency of AEsPrior systemic therapyAdoptive cell therapyUnresectable metastatic melanomaPreliminary dataAutologous tumorLymphodepletion regimenTIL treatmentMedian followProgressive diseaseComplete response
2017
Efficacy of single administration of tumor-infiltrating lymphocytes (TIL) in heavily pretreated patients with metastatic melanoma following checkpoint therapy.
Sarnaik A, Kluger H, Chesney J, Sethuraman J, Veerapathran A, Simpson-Abelson M, Lotze M, Larsen B, Fischkoff S, Suzuki S, Wang L, Mirgoli M, Fardis M, Curti B. Efficacy of single administration of tumor-infiltrating lymphocytes (TIL) in heavily pretreated patients with metastatic melanoma following checkpoint therapy. Journal Of Clinical Oncology 2017, 35: 3045-3045. DOI: 10.1200/jco.2017.35.15_suppl.3045.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesAdvanced metastatic melanomaMetastatic melanomaTIL productsPrior therapySafety profileIL-2Advanced metastatic melanoma patientsNon-hematologic grade 3Cell therapyPrior systemic therapyAcceptable safety profilePhase 2 studyMetastatic melanoma patientsAdoptive cell therapyEx vivo expansionEnlisted patientsRECIST 1.1Study patientsCheckpoint therapyMedian durationSurgical resectionSystemic therapyAutologous lymphocytesMedian age
2014
Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL).
Sznol M, Kluger H, Callahan M, Postow M, Gordon R, Segal N, Rizvi N, Lesokhin A, Atkins M, Kirkwood J, Burke M, Ralabate A, Rivera A, Kronenberg S, Agunwamba B, Feely W, Hong Q, Krishnan S, Gupta A, Wolchok J. Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL). Journal Of Clinical Oncology 2014, 32: lba9003-lba9003. DOI: 10.1200/jco.2014.32.18_suppl.lba9003.Peer-Reviewed Original ResearchClinical activityTreatment-related adverse eventsMT statusManageable safety profilePrior systemic therapyPhase I trialMajority of ptsBRAF mutation statusBRAF MTIPI therapyStage M1cPrior therapyMedian durationObjective responseSystemic therapyAdvanced melanomaAdverse eventsConcurrent therapyI trialOS ratesSafety profileTumor reductionTumor responseGrade 3Wk 24
2013
Survival and long-term follow-up of safety and response in patients (pts) with advanced melanoma (MEL) in a phase I trial of nivolumab (anti-PD-1; BMS-936558; ONO-4538).
Sznol M, Kluger H, Hodi F, McDermott D, Carvajal R, Lawrence D, Topalian S, Atkins M, Powderly J, Sharfman W, Puzanov I, Smith D, Wigginton J, Kollia G, Gupta A, Sosman J. Survival and long-term follow-up of safety and response in patients (pts) with advanced melanoma (MEL) in a phase I trial of nivolumab (anti-PD-1; BMS-936558; ONO-4538). Journal Of Clinical Oncology 2013, 31: cra9006-cra9006. DOI: 10.1200/jco.2013.31.18_suppl.cra9006.Peer-Reviewed Original ResearchPhase I trialI trialInhibitory immune checkpoint receptorsDrug-related AEsDrug-related diarrheaDrug-related pneumonitisAcceptable safety profilePhase III trialsOverall survival dataImmune checkpoint receptorsCycles of treatmentLong-term safetyMonoclonal antibody nivolumabActivated T cellsGr 3Cohort expansionECOG PSMedian OSPrior therapyIII trialsAdvanced melanomaAntibody nivolumabDose escalationPD-1Checkpoint receptorsSafety and clinical activity of nivolumab (anti-PD-1, BMS-936558, ONO-4538) in combination with ipilimumab in patients (pts) with advanced melanoma (MEL).
Wolchok J, Kluger H, Callahan M, Postow M, Gordon R, Segal N, Rizvi N, Lesokhin A, Reed K, Burke M, Caldwell A, Kronenberg S, Agunwamba B, Feely W, Hong Q, Horak C, Korman A, Wigginton J, Gupta A, Sznol M. Safety and clinical activity of nivolumab (anti-PD-1, BMS-936558, ONO-4538) in combination with ipilimumab in patients (pts) with advanced melanoma (MEL). Journal Of Clinical Oncology 2013, 31: 9012-9012. DOI: 10.1200/jco.2013.31.15_suppl.9012.Peer-Reviewed Original ResearchObjective response rateRelated adverse eventsPhase III trialsConcurrent therapyIII trialsPD-1Clinical activityCTLA-4/PDIpilimumab combination therapyCTLA-4 blockadeManageable safety profilePhase 1 studyPhase I trialImmune checkpoint receptorsIpilimumab therapyMonotherapy dataPrior therapySymptom resolutionAdverse eventsI trialAdvanced melanomaDurable CRCheckpoint receptorsSafety profileCombination therapySurvival, safety, and response duration results of nivolumab (Anti-PD-1; BMS-936558; ONO-4538) in a phase I trial in patients with previously treated metastatic renal cell carcinoma (mRCC): Long-term patient follow-up.
Drake C, McDermott D, Sznol M, Choueiri T, Kluger H, Powderly J, Smith D, Sankar V, Gutierrez A, Wigginton J, Kollia G, Gupta A, Atkins M. Survival, safety, and response duration results of nivolumab (Anti-PD-1; BMS-936558; ONO-4538) in a phase I trial in patients with previously treated metastatic renal cell carcinoma (mRCC): Long-term patient follow-up. Journal Of Clinical Oncology 2013, 31: 4514-4514. DOI: 10.1200/jco.2013.31.15_suppl.4514.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaOverall survivalDrug-related AEsGrade 3 pneumonitisMedian overall survivalAcceptable safety profilePhase III trialsPD-1 ligandsPhase I trialLong-term patientsPD-1 receptorImmune checkpoint receptorsRenal cell carcinomaLong-term safetyT cell activationPopulation of ptsPrior therapyTreatment discontinuationAdverse eventsIII trialsMedian durationUnacceptable toxicityComplete responseDeath-1I trial