2023
DTRMWXHS‐12, a novel Bruton tyrosine kinase inhibitor, in combination with everolimus and pomalidomide in patients with relapsed/refractory lymphomas: An open‐label, multicenter, phase 1a/1b study
Huntington S, Schuster S, Ding W, Koehler A, Brander D, Rosenthal A, Leis J, Tun H, Moustafa M, Iqbal M, He W, Kearney A, McKinlay T, Gui M, Mato A. DTRMWXHS‐12, a novel Bruton tyrosine kinase inhibitor, in combination with everolimus and pomalidomide in patients with relapsed/refractory lymphomas: An open‐label, multicenter, phase 1a/1b study. American Journal Of Hematology 2023, 98: 739-749. PMID: 36810799, DOI: 10.1002/ajh.26888.Peer-Reviewed Original ResearchConceptsBruton tyrosine kinase inhibitorsTyrosine kinase inhibitorsRefractory lymphomaTriplet combinationsKinase inhibitorsOral combination therapyPhase 2 doseOpen-label studyDose-escalation studyAccelerated titration designB-cell NHLNovel Bruton's tyrosine kinase inhibitorEligible patientsEverolimus 5Refractory CLLEscalation studyTriplet therapyMedian ageCombination therapyHodgkin's lymphomaIMiD therapyImmunomodulatory agentsClinical activityDoublet combinationsPreclinical studies
2020
A Once Daily, Oral, Triple Combination of BTK Inhibitor, mTOR Inhibitor and IMiD for Treatment of Relapsed/Refractory Richter's Transformation and De Novo Diffuse Large B-Cell Lymphoma
Mato A, Schuster S, Foss F, Isufi I, Kothari S, Ding W, Brander D, Sitlinger A, Rosenthal A, Leis J, Tun H, Kennard K, Nelson A, Falco V, Komari C, Koehler A, Stowe R, He W, Kearney A, Gui M, McKinlay T, Roeker L, Thompson M, Huntington S. A Once Daily, Oral, Triple Combination of BTK Inhibitor, mTOR Inhibitor and IMiD for Treatment of Relapsed/Refractory Richter's Transformation and De Novo Diffuse Large B-Cell Lymphoma. Blood 2020, 136: 21-22. DOI: 10.1182/blood-2020-138896.Peer-Reviewed Original ResearchB-cell lymphomaChronic lymphocytic leukemiaLarge B-cell lymphomaR DLBCLStem cell transplantDuration of responseRichter transformationCombination therapyPrior therapyUnmet medical needTriple combinationPrimary endpointOverall survivalF. Hoffmann-La RocheMedian age 71 yearsMedical needTyrosine kinase inhibitor monotherapyDe novo diffuse large B-cell lymphomaNovo diffuse large B-cell lymphomaIndolent B-cell lymphomaAdvisory CommitteeMajor unmet medical needDiffuse large B-cell lymphomaHoffmann-La RochePhase I
2019
A Phase Ia/Ib Study Exploring the Synthetic Lethality of the Orally Administered Novel BTK Inhibitor, Dtrmwxhs-12 (DTRM-12), in Combination with Everolimus and Pomalidomide in Patients with Relapsed/Refractory CLL, DLBCL or Other B-Cell Lymphomas
Mato A, Schuster S, Foss F, Isufi I, Ding W, Brander D, Sitlinger A, Tun H, Moustafa M, Kennard K, King C, Koehler A, Aitken C, He W, Kearney A, Gui M, Anderson B, Rosenthal A, Roeker L, Huntington S. A Phase Ia/Ib Study Exploring the Synthetic Lethality of the Orally Administered Novel BTK Inhibitor, Dtrmwxhs-12 (DTRM-12), in Combination with Everolimus and Pomalidomide in Patients with Relapsed/Refractory CLL, DLBCL or Other B-Cell Lymphomas. Blood 2019, 134: 810. DOI: 10.1182/blood-2019-126192.Peer-Reviewed Original ResearchChronic lymphocytic leukemiaB-cell lymphomaHodgkin's lymphomaRichter transformationCombination therapyCell lymphomaPrimary endpointRelapsed/Refractory Chronic Lymphocytic LeukemiaDose reduction/interruptionDose-limiting toxicity periodLow-dose combination therapyMedian age 70 yearsR CLLRefractory chronic lymphocytic leukemiaHigh unmet medical needPhase IMedian prior therapiesReduction/interruptionTriplet combination therapyUS multicenter studyAcceptable safety profileProgression-free survivalDaily oral administrationDurability of responseAge 70 years