2012
A phase 1 study of weekly dosing of trastuzumab emtansine (T‐DM1) in patients with advanced human epidermal growth factor 2–positive breast cancer
Beeram M, Krop IE, Burris HA, Girish SR, Yu W, Lu MW, Holden SN, Modi S. A phase 1 study of weekly dosing of trastuzumab emtansine (T‐DM1) in patients with advanced human epidermal growth factor 2–positive breast cancer. Cancer 2012, 118: 5733-5740. PMID: 22648179, DOI: 10.1002/cncr.27622.Peer-Reviewed Original ResearchConceptsHER2-positive metastatic breast cancerMetastatic breast cancerAdverse eventsT-DM1Breast cancerTrastuzumab emtansineObjective partial tumor responseTreatment-related adverse eventsClinical benefit rateDose-escalation studyPartial tumor responsePhase 1 studyTotal trastuzumabDose modificationMedian durationWeekly doseWeekly dosingAdditional patientsTumor responseBenefit rateHuman epidermal growth factorEpidermal growth factorPatientsGrowth factorAntitumor activityPhase I Pharmacologic and Pharmacodynamic Study of the Gamma Secretase (Notch) Inhibitor MK-0752 in Adult Patients With Advanced Solid Tumors
Krop I, Demuth T, Guthrie T, Wen PY, Mason WP, Chinnaiyan P, Butowski N, Groves MD, Kesari S, Freedman SJ, Blackman S, Watters J, Loboda A, Podtelezhnikov A, Lunceford J, Chen C, Giannotti M, Hing J, Beckman R, LoRusso P. Phase I Pharmacologic and Pharmacodynamic Study of the Gamma Secretase (Notch) Inhibitor MK-0752 in Adult Patients With Advanced Solid Tumors. Journal Of Clinical Oncology 2012, 30: 2307-2313. PMID: 22547604, DOI: 10.1200/jco.2011.39.1540.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsClinical benefitDose levelsSolid tumorsCommon drug-related toxicitiesGene signatureObjective complete responsePreliminary antitumor efficacyWeekly dose levelMaximum-tolerated doseDose-proportional mannerDrug-related toxicityHigh-grade gliomasHighest dose levelStable diseaseWeekly dosingAdult patientsComplete responseOral inhibitorNotch signalingCombination trialsNovel agentsPharmacodynamic studiesPatientsNotch pathway activation
2009
A phase I study of weekly dosing of trastuzumab-DM1 (T-DM1) in patients with advanced HER2+ breast cancer.
Krop I, Mita M, Burris H, Birkner M, Girish S, Tibbitts J, Holden S, Lutzker S, Modi S. A phase I study of weekly dosing of trastuzumab-DM1 (T-DM1) in patients with advanced HER2+ breast cancer. Cancer Research 2009, 69: 3136. DOI: 10.1158/0008-5472.sabcs-3136.Peer-Reviewed Original ResearchTrastuzumab-DM1Advanced HER2Antibody-drug conjugatesBreast cancerChemotherapy regimenCycle 1 day 1HER2 antibody-drug conjugatesFirst antibody-drug conjugatePhase IActivity of trastuzumabGrade 4 thrombocytopeniaReversible transaminase elevationT-DM1 exposureDose-escalation studyPhase II trialMeasurable diseaseQ3W dosingTransaminase elevationEscalation studyII trialPartial responseWeekly dosingCardiac toxicityTumor responseClinical trials
2008
A phase I study of weekly dosing of trastuzumab-DM1 (T-DM1) in patients (pts) with advanced HER2+ breast cancer (BC)
Holden S, Beeram M, Krop I, Burris H, Birkner M, Girish S, Tibbitts J, Lutzker S, Modi S. A phase I study of weekly dosing of trastuzumab-DM1 (T-DM1) in patients (pts) with advanced HER2+ breast cancer (BC). Journal Of Clinical Oncology 2008, 26: 1029-1029. DOI: 10.1200/jco.2008.26.15_suppl.1029.Peer-Reviewed Original Research