2025
A Phase I/IB Trial of Pembrolizumab and Trametinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Enriched for KRAS Mutations
Riess J, Lara M, Luxardi G, de Rodas M, Shimoda M, Kelly K, Lara P, Beckett L, Monjazeb A, Schalper K, Maverakis E, Gandara D. A Phase I/IB Trial of Pembrolizumab and Trametinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Enriched for KRAS Mutations. JTO Clinical And Research Reports 2025, 100806. DOI: 10.1016/j.jtocrr.2025.100806.Peer-Reviewed Original ResearchNon-small cell lung cancerAdvanced non-small cell lung cancerMEK inhibitionAdverse eventsProgressive diseaseKRAS mutationsMyeloid-derived suppressor cellsTrametinib 2 mgDose-escalation studyPlatinum-based chemotherapyImmune cell alterationsTumor immune microenvironmentPhase 1 studyCell lung cancerHigh-parameter flow cytometryArm BEscalation studyPartial responseArm ASuppressor cellsImmune microenvironmentPembrolizumabTrametinibQuantitative immunofluorescenceLung cancer
2024
A phase Ib study of the combination of naporafenib with rineterkib or trametinib in patients with advanced and metastatic KRAS- or BRAF-mutant non-small cell lung cancer
Planchard D, Wolf J, Solomon B, Sebastian M, Wermke M, Heist R, Sun J, Min Kim T, Reguart N, Sanmamed M, Felip E, Garrido P, Santoro A, Bootle D, Couillebault X, Gaur A, Mueller C, Poggio T, Yang J, Moschetta M, Dooms C. A phase Ib study of the combination of naporafenib with rineterkib or trametinib in patients with advanced and metastatic KRAS- or BRAF-mutant non-small cell lung cancer. Lung Cancer 2024, 197: 107964. PMID: 39383771, DOI: 10.1016/j.lungcan.2024.107964.Peer-Reviewed Original ResearchNon-small cell lung cancerCell lung cancerBRAF-mutated non-small cell lung cancerLung cancerDose-escalation/dose-expansion studyTreatment-related adverse eventsAntitumor activityDose-limiting toxicityNRAS-mutant melanomaMEK1/2 inhibitor trametinibPartial responseInhibitor trametinibFrequent gradeSafety profileAdverse eventsPharmacodynamic effectsTrametinibGenetic alterationsMedian reductionPan-RAFIncreased lipasePatientsSecondary objectivesMRNA levelsEvaluate toleranceA Single-Arm Phase 2 Trial of Trametinib in Patients with Locally Advanced or Metastatic Epithelioid Hemangioendothelioma.
Schuetze S, Ballman K, Heise R, Ganjoo K, Davis E, George S, Burgess M, Choy E, Shepard D, Tinoco G, Hirbe A, Kelly C, Attia S, Deshpande H, Schwartz G, Siontis B, Riedel R, von Mehren M, Kozlowski E, Chen H, Astbury C, Rubin B. A Single-Arm Phase 2 Trial of Trametinib in Patients with Locally Advanced or Metastatic Epithelioid Hemangioendothelioma. Clinical Cancer Research 2024, 30: 4584-4592. PMID: 38446990, PMCID: PMC11377863, DOI: 10.1158/1078-0432.ccr-23-3817.Peer-Reviewed Original ResearchEpithelioid hemangioendotheliomaMetastatic epithelioid hemangioendotheliomaMedian PFSOS ratesEvidence of tumor progressionPhase 2 trialMedian pain intensityEffects of trametinibMAPK pathwayActivation of MAPK pathwayInhibitor of MEKPalliative benefitPain intensityPain scoresPrimary endpointAssociated with reductionsTrametinibTumor progressionTumor samplesOncogenic driversVascular cancerPatientsPatient safetyResponse ratePFSTopical trametinib for epidermal and sebaceous nevi in a child with Schimmelpenning‐Feuerstein‐Mims syndrome
Haller C, Leszczynska M, Brichta L, Maier E, Riddington I, Choate K, Levy M. Topical trametinib for epidermal and sebaceous nevi in a child with Schimmelpenning‐Feuerstein‐Mims syndrome. Pediatric Dermatology 2024, 41: 523-525. PMID: 38273779, PMCID: PMC11096062, DOI: 10.1111/pde.15523.Peer-Reviewed Original ResearchCombined BET and MEK Inhibition synergistically suppresses melanoma by targeting YAP1
Hu R, Hou H, Li Y, Zhang M, Li X, Chen Y, Guo Y, Sun H, Zhao S, Liao M, Cao D, Yan Q, Chen X, Yin M. Combined BET and MEK Inhibition synergistically suppresses melanoma by targeting YAP1. Theranostics 2024, 14: 593-607. PMID: 38169595, PMCID: PMC10758063, DOI: 10.7150/thno.85437.Peer-Reviewed Original ResearchConceptsMEK inhibitor resistanceMEK inhibitor trametinibTrametinib treatmentInhibitor resistanceInhibitor trametinibMelanoma patientsYAP1 expressionMEK inhibitionBRAF-mutant melanoma patientsResistance to MEK inhibitionYAP1 inhibitionResistance to trametinibMelanoma growth <i>inInhibition of BRD4Trametinib resistanceAntitumor effectMelanoma growthTrametinibNHWD-870YAP1 inhibitorDrug resistanceMelanomaMelanoma samplesMelanoma cellsBRD4 depletion
2021
KRAS‐Mutated, Estrogen Receptor‐Positive Low‐Grade Serous Ovarian Cancer: Unraveling an Exceptional Response Mystery
Kato S, McFall T, Takahashi K, Bamel K, Ikeda S, Eskander R, Plaxe S, Parker B, Stites E, Kurzrock R. KRAS‐Mutated, Estrogen Receptor‐Positive Low‐Grade Serous Ovarian Cancer: Unraveling an Exceptional Response Mystery. The Oncologist 2021, 26: e530-e536. PMID: 33528846, PMCID: PMC8018312, DOI: 10.1002/onco.13702.Peer-Reviewed Original ResearchConceptsMEK inhibitorsMechanism of actionOvarian cancerAromatase inhibitorsEstrogen modulationKRAS-mutantLow-grade serous ovarian cancerCombination of trametinibEstrogen receptor-positiveSerous ovarian cancerPrecision medicine strategiesPI3K inhibitorsReceptor-positiveCombination therapyEstrogen depletionTamoxifenTrametinibAgonist effectsIn vitro investigationLetrozoleEstrogenIn vitro experimentsMedicine strategiesMEKExceptional responseP15.04 A Phase I/IB Trial of Pembrolizumab and Trametinib Focused on Advanced KRAS Mutant Non-Small Cell Lung Cancer
Riess J, Schalper K, Kelly K, Shimoda M, Luxardi G, Merleev A, Monjazeb A, Danenberg K, Maverakis E, Gandara D. P15.04 A Phase I/IB Trial of Pembrolizumab and Trametinib Focused on Advanced KRAS Mutant Non-Small Cell Lung Cancer. Journal Of Thoracic Oncology 2021, 16: s345. DOI: 10.1016/j.jtho.2021.01.541.Peer-Reviewed Original Research
2018
Response to the BRAF/MEK inhibitors dabrafenib/trametinib in an adolescent with a BRAF V600E mutated anaplastic ganglioglioma intolerant to vemurafenib
Marks AM, Bindra RS, DiLuna ML, Huttner A, Jairam V, Kahle KT, Kieran MW. Response to the BRAF/MEK inhibitors dabrafenib/trametinib in an adolescent with a BRAF V600E mutated anaplastic ganglioglioma intolerant to vemurafenib. Pediatric Blood & Cancer 2018, 65: e26969. PMID: 29380516, DOI: 10.1002/pbc.26969.Peer-Reviewed Original ResearchConceptsAnaplastic gangliogliomaBRAF/MEK inhibitor combinationsBRAF V600ESubsequent tumor responseDabrafenib/trametinibLarge clinical trialsSquamous cell carcinomaMEK inhibitor combinationsSignificant side effectsSignificant skin reactionsCell carcinomaCase reportSkin reactionsTumor responseClinical trialsBrain tumorsInhibitor combinationsSide effectsAdolescent femalesGangliogliomaTrametinibPrevious reactionsV600EMonotherapyRash
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