2024
Phase Ib dose-escalation trial of taselisib (GDC-0032) in combination with HER2-directed therapies in patients with advanced HER2+ breast cancer
Grinshpun A, Ren S, Graham N, DeMeo M, Wrabel E, Carter J, Tayob N, Pereslete A, Hamilton E, Juric D, Mayer E, Tolaney S, Krop I, Metzger O. Phase Ib dose-escalation trial of taselisib (GDC-0032) in combination with HER2-directed therapies in patients with advanced HER2+ breast cancer. ESMO Open 2024, 9: 103465. PMID: 38833970, PMCID: PMC11179085, DOI: 10.1016/j.esmoop.2024.103465.Peer-Reviewed Original ResearchProgression-free survivalMaximal tolerated doseHER2+ breast cancerAdverse eventsBreast cancerT-DM1Cohort AHuman epidermal growth factor receptor 2-positiveEpidermal growth factor receptor 2-positiveHER2+) breast cancerMedian progression-free survivalAll-grade adverse eventsAssociated with significant toxicityCirculating tumor DNA analysisDevelopment of acquired resistanceHER2-directed regimensHER2-directed therapyAnti-HER2 therapyHER2-targeted therapyPhase Ib studyTumor DNA analysisPI3KDose escalationImprove disease controlOral inhibitor
2021
A phase II study of efficacy, toxicity, and the potential impact of genomic alterations on response to eribulin mesylate in combination with trastuzumab and pertuzumab in women with human epidermal growth factor receptor 2 (HER2)+ metastatic breast cancer
Balch SM, Vaz-Luis I, Li T, Tayob N, Jain E, Helvie K, Buendia-Buendia JE, Shannon E, Isakoff SJ, Tung NM, Krop IE, Lin NU, Wagle N, Freedman RA. A phase II study of efficacy, toxicity, and the potential impact of genomic alterations on response to eribulin mesylate in combination with trastuzumab and pertuzumab in women with human epidermal growth factor receptor 2 (HER2)+ metastatic breast cancer. Breast Cancer Research And Treatment 2021, 189: 411-423. PMID: 34302589, DOI: 10.1007/s10549-021-06329-x.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 2Objective response ratePhase II studyWhole-exome sequencingEribulin 1.4II studyTreatment landscapeCohort AEribulin mesylateDay 1Genomic alterationsMetastatic breast cancer settingEpidermal growth factor receptor 2More frequent alterationsBreast cancer settingModest clinical activityGrowth factor receptor 2Metastatic breast cancerResponse/resistanceFactor receptor 2Manageable toxicityPertuzumab exposurePrimary endpointSix patientsCohort B
2020
Phase I dose-escalation trial of tucatinib in combination with trastuzumab in patients with HER2-positive breast cancer brain metastases
Filho O, Leone JP, Li T, Tan-Wasielewski Z, Trippa L, Barry WT, Younger J, Lawler E, Walker L, Freedman RA, Tolaney SM, Krop I, Winer EP, Lin NU. Phase I dose-escalation trial of tucatinib in combination with trastuzumab in patients with HER2-positive breast cancer brain metastases. Annals Of Oncology 2020, 31: 1231-1239. PMID: 32461105, DOI: 10.1016/j.annonc.2020.05.014.Peer-Reviewed Original ResearchConceptsClinical benefit rateHER2-positive brain metastasesAlanine aminotransferase elevationCohort ABrain metastasesCohort BAminotransferase elevationBreast cancerHER2-positive breast cancer brain metastasesPhase I dose-escalation trialMedian progression-free survivalBreast cancer brain metastasesCommon dose-limiting toxicityI dose-escalation trialHER2-positive breast cancerCombination of tucatinibSecondary end pointsCancer brain metastasesDose-escalation trialProgression-free survivalDose-limiting toxicityMetastatic breast cancerBrain radiationObjective responseIntracranial activity
2017
A phase II study of eribulin mesylate in combination with trastuzumab and pertuzumab in patients (pts) with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC).
Luis I, Guo H, Barry W, Krop I, Wagle N, Lowe A, Gore D, Andrews C, Osmani W, Isakoff S, Tung N, Winer E, Lin N, Freedman R. A phase II study of eribulin mesylate in combination with trastuzumab and pertuzumab in patients (pts) with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC). Journal Of Clinical Oncology 2017, 35: 1034-1034. DOI: 10.1200/jco.2017.35.15_suppl.1034.Peer-Reviewed Original ResearchMetastatic breast cancerOverall response ratePhase II studyStable diseasePertuzumab exposureAdverse eventsII studyCohort AHuman epidermal growth factor receptorActivity of eribulinDose of eribulinFrequent grade 3First-line settingMost adverse eventsAnti-HER2 therapyCorrelative studiesEpidermal growth factor receptorCell-free DNAGrowth factor receptorHematologic toxicityCohort studyOverall survivalPartial responseCohort BSingle center
2013
Phase II study of ruxolitinib in patients with pStat3+ breast cancer.
Lin N, Gelman R, Brock J, Bardia A, Mayer E, Overmoyer B, Wang V, Iannone M, Krop I, Polyak K, Winer E. Phase II study of ruxolitinib in patients with pStat3+ breast cancer. Journal Of Clinical Oncology 2013, 31: tps1134-tps1134. DOI: 10.1200/jco.2013.31.15_suppl.tps1134.Peer-Reviewed Original ResearchBreast cancerObjective responseCohort BCohort AOpen-label phase 2 trialIL-6/JAK2/STAT3Tumor tissueM.D. Anderson Symptom InventoryTriple-negative breast cancerAdequate organ functionBaseline tumor biopsiesECOG PS 0High-risk myelofibrosisPhase II studyEORTC QLQ CPhase 2 trialInflammatory breast cancerArchival tumor tissueWk 4JAK2/STAT3Further studiesAccessible diseaseMeasurable diseasePrior therapyPrimary endpoint