2025
Phase II Trial of Pembrolizumab in Combination With Bevacizumab for Untreated Melanoma Brain Metastases.
Weiss S, Djureinovic D, Wei W, Tran T, Austin M, Markowitz J, Eroglu Z, Khushalani N, Hegde U, Cohen J, Sznol M, Anderson G, Johnson B, Piteo C, Mahajan A, Adeniran A, Jilaveanu L, Goldberg S, Chiang V, Forsyth P, Kluger H. Phase II Trial of Pembrolizumab in Combination With Bevacizumab for Untreated Melanoma Brain Metastases. Journal Of Clinical Oncology 2025, jco2402219. PMID: 40048689, DOI: 10.1200/jco-24-02219.Peer-Reviewed Original ResearchMelanoma brain metastasesOverall survivalBrain metastasesAnti-vascular endothelial growth factor therapyMedian intracranial progression-free survivalFour-year OS ratesIntracranial progression-free survivalResponse rateCirculating angiopoietin-2Median overall survivalTrial of pembrolizumabYears of pembrolizumabDose of bevacizumabProgression-free survivalPhase II trialGrowth factor therapyAdverse event ratesAssociated with responseOS ratesPD-1Radiation necrosisLocal therapyOn-therapyMetastatic tumorsFactor therapyHER2DX in HER2-positive inflammatory breast cancer: correlative insights and comparative analysis with noninflammatory breast cancers ☆
Lynce F, Martínez-Sáez O, Walbaum B, Brasó-Maristany F, Waks A, Villagrasa P, Javierre G, Sanfeliu E, Galván P, Paré L, Anderson L, Perou C, Parker J, Vivancos A, DiLullo M, Pernas S, Winer E, Overmoyer B, Mittendorf E, Bueno-Muiño C, Martín M, Prat A, Tolaney S. HER2DX in HER2-positive inflammatory breast cancer: correlative insights and comparative analysis with noninflammatory breast cancers ☆. ESMO Open 2025, 10: 104100. PMID: 39826476, PMCID: PMC11786065, DOI: 10.1016/j.esmoop.2024.104100.Peer-Reviewed Original ResearchHER2-positive inflammatory breast cancerPathological complete responseInflammatory breast cancerNeoadjuvant systemic therapyNon-IBCBreast cancerSystemic therapyEarly-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancerPredictors of pathologic complete responseHuman epidermal growth factor receptor 2 (HER2)-positive breast cancerIBC cohortIBC statusPathologic complete response rateLow axillary burdenNoninflammatory breast cancerTrastuzumab-based chemotherapyTreatment de-escalationPhase II trialClinical-pathological featuresLong-term prognosisPCR scoreAxillary burdenNeoadjuvant trastuzumabPCR rateComplete response
2024
Isatuximab in Relapsed AL Amyloidosis: Results of a Prospective Phase II Trial (SWOG S1702)
Parker T, Rosenthal A, Sanchorawala V, Landau H, Campagnaro E, Kapoor P, Neparidze N, Girnius S, Hagen P, Scott E, Hoering A, Durie B, Orlowski R. Isatuximab in Relapsed AL Amyloidosis: Results of a Prospective Phase II Trial (SWOG S1702). Blood 2024, 144: 3378-3378. DOI: 10.1182/blood-2024-208341.Peer-Reviewed Original ResearchMedian time to responseRelapsed AL amyloidosisTime to responseAL amyloidosisPartial responseHematologic responseComplete responseCardiac involvementOverall survivalRenal involvementOrgan involvementEastern Cooperative Oncology Group performance statusRate of hematologic responseAutologous stem cell transplantationProspective phase II trialLight chain (AL) amyloidosisDistribution of organ involvementProgression free survivalHematologic complete responseHematologic response rateStem cell transplantationPhase II trialAnti-CD38 antibodiesSystemic AL amyloidosisRate of patientsEfficacy and Safety of Pembrolizumab Added to Azacitidine Plus Venetoclax for Patients with Acute Myeloid Leukemia: Results from an Investigator-Initiated, Multi-Center, CTEP-Sponsored Randomized, Phase II Trial (BLAST AML-2)
Stempel J, Uy G, Dinner S, Gojo I, Reed D, Roy R, Byrd K, Yerrabothala S, Lai C, Doucette K, Caldwell A, Blaha O, Podoltsev N, Mendez L, Bewersdorf J, Kewan T, Wistuba I, Alatrash G, Haymaker C, Streicher H, Sharon E, Little R, Gore S, Radich J, Wood B, Zeidan A, Shallis R. Efficacy and Safety of Pembrolizumab Added to Azacitidine Plus Venetoclax for Patients with Acute Myeloid Leukemia: Results from an Investigator-Initiated, Multi-Center, CTEP-Sponsored Randomized, Phase II Trial (BLAST AML-2). Blood 2024, 144: 736. DOI: 10.1182/blood-2024-210370.Peer-Reviewed Original ResearchPhase II trialTreatment-related AEsII trialFrequent treatment-related AEsSafety run-in periodAllogeneic stem cell transplantationNo dose limiting toxicitiesRandomized phase II trialAML-2Multi-centerControl armSafety of pembrolizumabDose-limiting toxicityPD-1 inhibitionAnti-PD1 antibodyIncomplete count recoveryFLT3 wild-typeIntermediate cytogenetic riskStem cell transplantationAcute myeloid leukemiaActivated T cellsRun-in periodIntention-to-treat analysisCancer Immune MonitoringLong-term survivalNeoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial
Davar D, Morrison R, Dzutsev A, Karunamurthy A, Chauvin J, Amatore F, Deutsch J, Das Neves R, Rodrigues R, McCulloch J, Wang H, Hartman D, Badger J, Fernandes M, Bai Y, Sun J, Cole A, Aggarwal P, Fang J, Deitrick C, Bao R, Duvvuri U, Sridharan S, Kim S, A Choudry H, Holtzman M, Pingpank J, O'Toole J, DeBlasio R, Jin Y, Ding Q, Gao W, Groetsch C, Pagliano O, Rose A, Urban C, Singh J, Divarkar P, Mauro D, Bobilev D, Wooldridge J, Krieg A, Fury M, Whiteaker J, Zhao L, Paulovich A, Najjar Y, Luke J, Kirkwood J, Taube J, Park H, Trinchieri G, Zarour H. Neoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial. Cancer Cell 2024, 42: 1898-1918.e12. PMID: 39486411, PMCID: PMC11560503, DOI: 10.1016/j.ccell.2024.10.007.Peer-Reviewed Original ResearchConceptsPlasmacytoid dendritic cellsHigh-risk resected melanomaResected melanomaCD8<sup>+</sup> tumor-infiltrating lymphocytesAnti-PD-1 nivolumabAnti-tumor immune responseProspective phase II trialAnti-PD-1Associated with gene signaturesTumor-infiltrating lymphocytesPhase II trialResponse to therapySingle-arm studyAssociated with necrosisGut microbiotaClinical responseII trialPrimary endpointDendritic cellsTLR9 agonistsTumor microenvironmentT cellsMyeloid cellsPathological responseImmune activationNivolumab plus anlotinib hydrochloride in advanced gastric adenocarcinoma and esophageal squamous cell carcinoma: the phase II OASIS trial
Wu J, Zhang S, Yu S, An G, Wang Y, Yu Y, Liang L, Wang Y, Xu X, Xiong Y, Shao D, Shi Z, Li N, Wang J, Jin D, Liu T, Cui Y. Nivolumab plus anlotinib hydrochloride in advanced gastric adenocarcinoma and esophageal squamous cell carcinoma: the phase II OASIS trial. Nature Communications 2024, 15: 8876. PMID: 39406730, PMCID: PMC11480398, DOI: 10.1038/s41467-024-53109-4.Peer-Reviewed Original ResearchConceptsEsophageal squamous cell carcinomaAdvanced gastric adenocarcinomaSquamous cell carcinomaTyrosine kinase inhibitorsGastric adenocarcinomaVariant allele frequencyAnlotinib hydrochlorideCell carcinomaVascular endothelial growth factor inhibitorsAnti-PD-1 antibodySafety of nivolumabAnti-PD-1Disease control rateMedian overall survivalProgression-free survivalGrowth factor inhibitorsPhase II trialOverall response rateOASIS trialPD-1Second-lineOverall survivalImmune signaturesII trialFactor inhibitorsA Phase II Study of Atezolizumab, Pertuzumab, and High-Dose Trastuzumab for Central Nervous System Metastases in Patients with HER2-Positive Breast Cancer
Giordano A, Kumthekar P, Jin Q, Kurt B, Ren S, Li T, Leone J, Mittendorf E, Pereslete A, Sharp L, Davis R, DiLullo M, Tayob N, Mayer E, Winer E, Tolaney S, Lin N. A Phase II Study of Atezolizumab, Pertuzumab, and High-Dose Trastuzumab for Central Nervous System Metastases in Patients with HER2-Positive Breast Cancer. Clinical Cancer Research 2024, 30: of1-of10. PMID: 39226397, PMCID: PMC11528201, DOI: 10.1158/1078-0432.ccr-24-1161.Peer-Reviewed Original ResearchHER2-positive breast cancer brain metastasesBreast cancer brain metastasesClinical benefit rateCancer brain metastasesCentral nervous systemCNS responseBrain metastasesOverall response rateOverall survivalAny-grade adverse eventsEffective systemic therapy optionsNeuro-Oncology Brain MetastasesHER2-positive breast cancerIntracranial partial responseSystemic therapy optionsPhase II studyPhase II trialCNS ORRRANO-BMDose delaysPartial responseII studyPrimary endpointHigh-doseBenefit ratePhase II Trial of Afatinib in Patients With EGFR-Mutated Solid Tumors Excluding Lung Cancer: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol A
Gettinger S, Song Z, Reckamp K, Moscow J, Gray R, Wang V, McShane L, Rubinstein L, Patton D, Williams P, Hamilton S, Kong X, Tricoli J, Conley B, Arteaga C, Harris L, O'Dwyer P, Chen A, Flaherty K. Phase II Trial of Afatinib in Patients With EGFR-Mutated Solid Tumors Excluding Lung Cancer: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol A. JCO Precision Oncology 2024, 8: e2300725. PMID: 38986051, DOI: 10.1200/po.23.00725.Peer-Reviewed Original ResearchConceptsProgression-free survivalTyrosine kinase inhibitorsEGFR tyrosine kinase inhibitorsNCI-MATCHLung cancerGlioblastoma multiformeOverall survivalAdvanced non-small cell lung cancerNational Cancer Institute-Molecular AnalysisNon-small cell lung cancerEnd pointsTumor genomic testingTrial primary end pointPhase 2 trialPhase II trialSecondary end pointsPrimary end pointCell lung cancerCohort of patientsMedian OSStable diseaseAdenosquamous carcinomaProtocol therapyPartial responseArm APatterns of brain metastases response to immunotherapy with pembrolizumab
Mahajan A, Goldberg S, Weiss S, Tran T, Singh K, Joshi K, Aboian M, Kluger H, Chiang V. Patterns of brain metastases response to immunotherapy with pembrolizumab. Journal Of Neuro-Oncology 2024, 169: 555-561. PMID: 38963658, DOI: 10.1007/s11060-024-04754-8.Peer-Reviewed Original ResearchNon-small cell lung cancerBrain metastasesComplete resolutionLung cancerMedian time to CNS progressionLesion progressionNon-small cell lung cancer patientsModified RECIST criteriaPD-1 inhibitorsTrial of pembrolizumabEffective systemic treatmentResponse to immunotherapyPhase II trialCell lung cancerMethodsThis retrospective studyLocal treatment decisionsPurposeCentral nervous systemCNS progressionRECIST criteriaPD-1Local therapySystemic treatmentMRI evaluationResponse assessmentRetrospective studyA 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 mutationsCompletion Rate and Positive Results Reporting Among Immunotherapy Trials in Breast Cancer, 2004-2023
Mariani M, Viale G, Galbardi B, Licata L, Bosi C, Dugo M, Notini G, Naldini M, Callari M, Criscitiello C, Pusztai L, Bianchini G. Completion Rate and Positive Results Reporting Among Immunotherapy Trials in Breast Cancer, 2004-2023. JAMA Network Open 2024, 7: e2423390. PMID: 39028669, PMCID: PMC11259908, DOI: 10.1001/jamanetworkopen.2024.23390.Peer-Reviewed Original ResearchConceptsCross-sectional studyPhase III trialsIII trialsBreast cancerImmunotherapy trialsLandscape of breast cancerPhase II studyPhase II trialPhase I trialSingle-center studySingle-center trialCancer immunotherapy trialsBreast cancer trialsPatient confidenceMain OutcomesFisher's exact testImmuno-oncology trialsTrial featuresProportion of trialsCompletion ratesAdjuvant settingPhase IIReport outcomesII trialPositive resultsAuthor Correction: TLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial
Everson R, Hugo W, Sun L, Antonios J, Lee A, Ding L, Bu M, Khattab S, Chavez C, Billingslea-Yoon E, Salazar A, Ellingson B, Cloughesy T, Liau L, Prins R. Author Correction: TLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial. Nature Communications 2024, 15: 4800. PMID: 38839763, PMCID: PMC11153605, DOI: 10.1038/s41467-024-48995-7.Peer-Reviewed Original ResearchA phase II trial of UGT1A1 genotype-guided FOLFIRI plus bevacizumab as first-line therapy for advanced, unresectable colorectal cancer
Sanoff H, Deal A, Patel J, Sorah J, Gaddy J, O’Neil B, Turk A, Irvin W, Boles J, Lee M, McRee A, Wardell A, Weck K, Basch E, Wood W, Innocenti F. A phase II trial of UGT1A1 genotype-guided FOLFIRI plus bevacizumab as first-line therapy for advanced, unresectable colorectal cancer. The Oncologist 2024, 29: 786-793. PMID: 38837045, PMCID: PMC11379652, DOI: 10.1093/oncolo/oyae122.Peer-Reviewed Original ResearchProgression-free survivalMetastatic colorectal cancerOverall survivalIrinotecan doseColorectal cancerMedian progression-free survivalMetastatic colorectal cancer patientsEstimates of overall survivalFirst-line settingUnresectable colorectal cancerRates of neutropeniaFirst-line therapyPhase II trialPatient-reported adverse eventsRate of diarrheaG3/4 toxicitiesUGT1A1 genotypeIrinotecan metabolismFirst-linePrimary endpointSecondary endpointsAdverse eventsFOLFIRIHistorical controlsNon-genotypeTP53 Mutations in Acute Leukemias and Myelodysplastic Syndromes: Insights and Treatment Updates.
Santini V, Stahl M, Sallman D. TP53 Mutations in Acute Leukemias and Myelodysplastic Syndromes: Insights and Treatment Updates. American Society Of Clinical Oncology Educational Book 2024, 44: e432650. PMID: 38768424, DOI: 10.1200/edbk_432650.Peer-Reviewed Original ResearchConceptsMissense mutationsResistant to current chemotherapyLoss-of-function effectPhase II trialPhase III trialsAnti-CD47 antibodyAnti-CD123 antibodyResponse to treatmentPressure of chemotherapyApoptosis systemP53 functionChromosome lossTP53 mutationsTruncating mutationsInhibitor therapyMyelodysplastic syndromeOverall survivalII trialIII trialsSelection pressureAnti-CD123Acute leukemiaAML casesDismal diseaseImproved survivalLong-term follow up of E3311, a phase II trial of transoral surgery (TOS) followed by pathology-based adjuvant treatment in HPV-associated (HPV+) oropharynx cancer (OPC): A trial of the ECOG-ACRIN Cancer Research Group.
Burtness B, Flamand Y, Quon H, Weinstein G, Mehra R, Garcia J, Kim S, O'malley B, Ozer E, Koch W, Gross N, Bell R, Patel M, Lango M, Morris L, Smith R, Karakla D, Richmon J, Holsinger F, Ferris R. Long-term follow up of E3311, a phase II trial of transoral surgery (TOS) followed by pathology-based adjuvant treatment in HPV-associated (HPV+) oropharynx cancer (OPC): A trial of the ECOG-ACRIN Cancer Research Group. Journal Of Clinical Oncology 2024, 42: 6009-6009. DOI: 10.1200/jco.2024.42.16_suppl.6009.Peer-Reviewed Original ResearchProgression-free survivalIntermediate risk patientsExtranodal extensionOverall survivalPhase II trialRisk patientsSmoking historyPack-yearsPrimary siteLong-term follow-upFavorable pathologic characteristicsMature outcome dataPrescribed radiation doseECOG-ACRIN Cancer Research GroupPost-operative radiationIncreased recurrence riskKaplan-Meier methodLog-rank testPost-operative managementCancer Research GroupHPV+ OPCWeekly cisplatinMedian followN1 diseaseN1 patientsSWOG S2302, PRAGMATICA-LUNG: A prospective randomized study of ramucirumab plus pembrolizumab (PR) versus standard of care (SOC) for participants previously treated with immunotherapy for stage IV or recurrent non-small cell lung cancer.
Reckamp K, Redman M, Dragnev K, Iams W, Henick B, Miao J, LeBlanc M, Carrizosa D, Herbst R, Blanke C, Gray J. SWOG S2302, PRAGMATICA-LUNG: A prospective randomized study of ramucirumab plus pembrolizumab (PR) versus standard of care (SOC) for participants previously treated with immunotherapy for stage IV or recurrent non-small cell lung cancer. Journal Of Clinical Oncology 2024, 42: tps8657-tps8657. DOI: 10.1200/jco.2024.42.16_suppl.tps8657.Peer-Reviewed Original ResearchNon-small cell lung cancerAdvanced non-small cell lung cancerStandard of careCell lung cancerPD-(L)1Overall survivalAdverse eventsRecurrent non-small cell lung cancerLung cancerTreatment-related adverse eventsRandomized phase II trialStandard of care treatmentPlatinum-based therapyTreated with immunotherapyPhase II trialLog-rank testCompare OSInhibitor therapyII trialCombination therapyStatistically significant improvementTumor resistanceSafety profileTherapeutic optionsRandomized studyPhase II trial of regorafenib in metastatic medullary thyroid carcinoma (MTC) and radioactive iodine refractory differentiated thyroid carcinoma (RAIR DTC).
Sehgal K, Shi R, Pappa T, Min J, Oakley L, ONeill A, Dennis M, Deshpande H, Haddad R, Lorch J. Phase II trial of regorafenib in metastatic medullary thyroid carcinoma (MTC) and radioactive iodine refractory differentiated thyroid carcinoma (RAIR DTC). Journal Of Clinical Oncology 2024, 42: 6109-6109. DOI: 10.1200/jco.2024.42.16_suppl.6109.Peer-Reviewed Original ResearchMetastatic medullary thyroid carcinomaTreatment-related adverse eventsProgression-free survivalRAIR-DTCProgression-freeOverall survivalClinical trialsMedian progression-free survivalCycle 2 onwardsMedian overall survivalPhase II clinical trialMedullary thyroid carcinomaPhase II trialMulti-kinase inhibitorII clinical trialsSimon's two-stage designRECIST v1.1Systemic therapyTolerated doseStage 2Thyroid carcinomaMedian agePlanned escalationTherapeutic optionsInhibitor exposureA phase Ib/II study of an anti-CD137 agonist antibody ADG106 in combination with weekly paclitaxel and dose-dense doxorubicin/cyclophosphamide.
Lee M, Ow S, Wong A, Lim S, Lim J, Soo R, Cheng Ean C, Tan D, Yong W, Chan G, Ho J, Sooi K, Low Q, Ang C, Cheo S, Sundar R, Goh B, Lee S. A phase Ib/II study of an anti-CD137 agonist antibody ADG106 in combination with weekly paclitaxel and dose-dense doxorubicin/cyclophosphamide. Journal Of Clinical Oncology 2024, 42: e14507-e14507. DOI: 10.1200/jco.2024.42.16_suppl.e14507.Peer-Reviewed Original ResearchAdverse eventsG3 neutropeniaTumor biopsiesWeekly PPeripheral neuropathyHER2 negative breast cancer patientsPhase IbDose levelsRecommended phase 2 doseAll-grade adverse eventsNegative breast cancer patientsMatched tumor biopsiesPhase 2 doseTumor immune markersPneumocystis jiroveci pneumoniaAdvanced solid tumorsPalliative systemic therapyPhase Ib trialPhase II trialPhase IISerial tumor biopsiesBreast cancer patientsIgG4 monoclonal antibodyAcneiform rashAnti-CD137TBCRC 048 (olaparib expanded) expansion cohorts: Phase 2 study of olaparib monotherapy in patients (pts) with metastatic breast cancer (MBC) with germline (g) mutations in PALB2 or somatic (s) mutations in BRCA1 or BRCA2.
Tung N, Robson M, Nanda R, Li T, Vinayak S, Shah P, Khoury K, Kimmick G, Santa-Maria C, Brufsky A, DeMeo M, Vieira J, Carey L, Wulf G, Domchek S, Krop I, Wolff A, Winer E, Garber J. TBCRC 048 (olaparib expanded) expansion cohorts: Phase 2 study of olaparib monotherapy in patients (pts) with metastatic breast cancer (MBC) with germline (g) mutations in PALB2 or somatic (s) mutations in BRCA1 or BRCA2. Journal Of Clinical Oncology 2024, 42: 1021-1021. DOI: 10.1200/jco.2024.42.16_suppl.1021.Peer-Reviewed Original ResearchProgression-free survivalDuration of responseMetastatic breast cancerClinical benefit rateTriple-negative breast cancerMedian duration of responseMedian progression-free survivalMutant allele frequencyExpansion cohortHER2-negativeHER2-positiveCohort 2aNon-respondersBreast cancerEarly due to slow enrollmentMetastatic chemotherapy regimensResponse to olaparibPhase 2 studyPhase II trialKaplan-Meier methodPredictors of responseCohort of womenWilcoxon rank sum testRank sum testBRCA1mETHAN: A phase II study comparing different endocrine therapies for male breast cancer.
Leone J, Ruddy K, Rashid N, Giordano S, Gupta G, Hilsenbeck S, Gucalp A, Walsh E, Sukumar J, Makhlin I, Ortiz-Perez T, Spanheimer P, Calhoun B, Wolff A, Krop I, Thompson A. ETHAN: A phase II study comparing different endocrine therapies for male breast cancer. Journal Of Clinical Oncology 2024, 42: tps632-tps632. DOI: 10.1200/jco.2024.42.16_suppl.tps632.Peer-Reviewed Original ResearchResidual cancer burdenMale breast cancerPreoperative endocrine prognostic indexTranslational Breast Cancer Research ConsortiumBreast cancerEndocrine therapyKi-67Patient-reported outcomesNeoadjuvant phaseArm BAromatase inhibitorsHuman epidermal growth factor receptor 2 (HER2)-negative breast cancerOutcome of endocrine therapyResidual cancer burden indexWindow phaseCyclin-dependent kinase 4/6Ki-67 reductionHormone receptor-positivePhase II studyInflammatory breast cancerLack of clinical trialsPhase II trialHR+/HER2- breast cancerAnti-cancer therapyStandard of care
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