2017
A randomized, double-blinded, controlled study of tucatinib (ONT-380) vs. placebo in combination with capecitabine (C) and trastuzumab (Tz) in patients with pretreated HER2+ unresectable locally advanced or metastatic breast carcinoma (mBC) (HER2CLIMB).
Anders C, Murthy R, Hamilton E, Borges V, Cameron D, Carey L, Müller V, Curigliano G, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pivot X, Pegram M, Slamon D, Hurvitz S, Tsai M, Winer E. A randomized, double-blinded, controlled study of tucatinib (ONT-380) vs. placebo in combination with capecitabine (C) and trastuzumab (Tz) in patients with pretreated HER2+ unresectable locally advanced or metastatic breast carcinoma (mBC) (HER2CLIMB). Journal Of Clinical Oncology 2017, 35: tps1107-tps1107. DOI: 10.1200/jco.2017.35.15_suppl.tps1107.Peer-Reviewed Original ResearchProgression-free survivalMetastatic breast carcinomaBrain metsIndependent data monitoring committeeClinical benefit ratePhase 1b studyDuration of responseIndependent central reviewPrimary study objectiveData monitoring committeeCNS progressionEGFR agentsPo bidBrain metastasesAdult patientsObjective responseOverall survivalCentral reviewStudy treatmentT-DM1CNS therapyTrastuzumab emtansineBenefit rateSelective small molecule inhibitorsBreast carcinoma
2012
Phase 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