Italiano A, Soria JC, Toulmonde M, Michot JM, Lucchesi C, Varga A, Coindre JM, Blakemore SJ, Clawson A, Suttle B, McDonald AA, Woodruff M, Ribich S, Hedrick E, Keilhack H, Thomson B, Owa T, Copeland RA, Ho PTC, Ribrag V (2018) Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study. Lancet Oncol 19(5):649–659. https://doi.org/10.1016/S1470-2045(18)30145-1

Article  CAS  PubMed  Google Scholar 

U.S. Department of Health and Human Services Food and Drug Administration (2020) NDA/BLA Multi-Disciplinary Review and Evaluation 213400; Tazverik (tazemetostat) U.S.Department of Health and Human Services; Food and Drug Administration; Center for Drug Evaluation and Research, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213400Orig1s000MultidisciplineR.pdf

U.S. Department of Health and Human Services Food and Drug Administration (2020) NDA 211723 NME - Multi-disciplinary Review and Evaluation TAZVERIK (tazemetostat). U.S.Department of Health and Human Services; Food and Drug Administration; Center for Drug Evaluation and Research, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf.

U.S. Department of Health and Human Services Food and Drug Administration (2020) LABELING: 213400 TAZVERIK; tazemetostat. U.S. Department of Health and Human Services; Food and Drug Administration; Center for Drug Evaluation and Research, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213400Orig1s000lbl.pdf.

Gounder M, Schoffski P, Jones RL, Agulnik M, Cote GM, Villalobos VM, Attia S, Chugh R, Chen TW, Jahan T, Loggers ET, Gupta A, Italiano A, Demetri GD, Ratan R, Davis LE, Mir O, Dileo P, Van Tine BA, Pressey JG, Lingaraj T, Rajarethinam A, Sierra L, Agarwal S, Stacchiotti S (2020) Tazemetostat in advanced epithelioid sarcoma with loss of INI1/SMARCB1: an international, open-label, phase 2 basket study. Lancet Oncol 21(11):1423–1432. https://doi.org/10.1016/S1470-2045(20)30451-4

Article  CAS  PubMed  Google Scholar 

Morschhauser F, Tilly H, Chaidos A, McKay P, Phillips T, Assouline S, Batlevi CL, Campbell P, Ribrag V, Damaj GL, Dickinson M, Jurczak W, Kazmierczak M, Opat S, Radford J, Schmitt A, Yang J, Whalen J, Agarwal S, Adib D, Salles G (2020) Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial. Lancet Oncol 21(11):1433–1442. https://doi.org/10.1016/S1470-2045(20)30441-1

Article  CAS  PubMed  PubMed Central  Google Scholar 

Proudman DG, Gupta D, Nellesen D, Yang J, Kamp BA, Mamlouk K, Cheson BD (2022) Tazemetostat in relapsed/refractory follicular lymphoma: a propensity score-matched analysis of E7438–G000-101 trial outcomes. Oncotarget 13:677–683. https://doi.org/10.18632/oncotarget.28229

Article  PubMed  PubMed Central  Google Scholar 

Knutson SK, Warholic NM, Wigle TJ, Klaus CR, Allain CJ, Raimondi A, Porter Scott M, Chesworth R, Moyer MP, Copeland RA, Richon VM, Pollock RM, Kuntz KW, Keilhack H (2013) Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2. Proc Natl Acad Sci USA 110(19):7922–7927. https://doi.org/10.1073/pnas.1303800110

Article  PubMed  PubMed Central  Google Scholar 

Chan-Penebre E, Armstrong K, Drew A, Grassian AR, Feldman I, Knutson SK, Kuplast-Barr K, Roche M, Campbell J, Ho P, Copeland RA, Chesworth R, Smith JJ, Keilhack H, Ribich SA (2017) Selective killing of SMARCA2- and SMARCA4-deficient small cell carcinoma of the ovary, hypercalcemic type cells by inhibition of EZH2: in vitro and in vivo preclinical models. Mol Cancer Ther 16(5):850–860. https://doi.org/10.1158/1535-7163.MCT-16-0678

Article  CAS  PubMed  Google Scholar 

Knutson SK, Kawano S, Minoshima Y, Warholic NM, Huang KC, Xiao Y, Kadowaki T, Uesugi M, Kuznetsov G, Kumar N, Wigle TJ, Klaus CR, Allain CJ, Raimondi A, Waters NJ, Smith JJ, Porter-Scott M, Chesworth R, Moyer MP, Copeland RA, Richon VM, Uenaka T, Pollock RM, Kuntz KW, Yokoi A, Keilhack H (2014) Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma. Mol Cancer Ther 13(4):842–854. https://doi.org/10.1158/1535-7163.MCT-13-0773

Article  CAS  PubMed  Google Scholar 

Kawano S, Grassian AR, Tsuda M, Knutson SK, Warholic NM, Kuznetsov G, Xu S, Xiao Y, Pollock RM, Smith JS, Kuntz KK, Ribich S, Minoshima Y, Matsui J, Copeland RA, Tanaka S, Keilhack H (2016) Preclinical evidence of anti-tumor activity induced by EZH2 inhibition in human models of synovial sarcoma. PLoS ONE 11(7):e0158888. https://doi.org/10.1371/journal.pone.0158888

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li H, Wang YJ, Geng XN, Kang YR, Wang YL, Qiu XJ (2022) Pharmacokinetics of herb-drug interactions of plumbagin and tazemetostat in rats by UPLC-MS/MS. Drug Des Devel Ther 16:3385–3394. https://doi.org/10.2147/DDDT.S384156

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kurmasheva RT, Sammons M, Favours E, Wu J, Kurmashev D, Cosmopoulos K, Keilhack H, Klaus CR, Houghton PJ, Smith MA (2017) Initial testing (stage 1) of tazemetostat (EPZ-6438) a novel EZH2 inhibitor, by the pediatric preclinical testing program. Pediatric Blood Cancer. https://doi.org/10.1002/pbc.26218

Article  PubMed  PubMed Central  Google Scholar 

Passeri T, Dahmani A, Masliah-Planchon J, Naguez A, Michou M, El Botty R, Vacher S, Bouarich R, Nicolas A, Polivka M, Franck C, Schnitzler A, Nemati F, Roman-Roman S, Bourdeaut F, Adle-Biassette H, Mammar H, Froelich S, Bieche I, Decaudin D (2022) Dramatic in vivo efficacy of the EZH2-inhibitor tazemetostat in PBRM1-mutated human Chordoma Xenograft. Cancers (Basel). https://doi.org/10.3390/cancers14061486

Article  PubMed  Google Scholar 

Zauderer MG, Szlosarek PW, Le Moulec S, Popat S, Taylor P, Planchard D, Scherpereel A, Koczywas M, Forster M, Cameron RB, Peikert T, Argon EK, Michaud NR, Szanto A, Yang J, Chen Y, Kansra V, Agarwal S, Fennell DA (2022) EZH2 inhibitor tazemetostat in patients with relapsed or refractory, BAP1-inactivated malignant pleural mesothelioma: a multicentre, open-label, phase 2 study. Lancet Oncol 23(6):758–767. https://doi.org/10.1016/S1470-2045(22)00277-7

Article  CAS  PubMed  Google Scholar 

Sarkozy C, Morschhauser F, Dubois S, Molina T, Michot JM, Cullieres-Dartigues P, Suttle B, Karlin L, Le Gouill S, Picquenot JM, Dubois R, Tilly H, Herbaux C, Jardin F, Salles G, Ribrag V (2020) A LYSA phase Ib study of tazemetostat (EPZ-6438) plus R-CHOP in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) with poor prognosis features. Clin Cancer Res 26(13):3145–3153. https://doi.org/10.1158/1078-0432.CCR-19-3741

Article  CAS  PubMed  Google Scholar 

Munakata W, Shirasugi Y, Tobinai K, Onizuka M, Makita S, Suzuki R, Maruyama D, Kawai H, Izutsu K, Nakanishi T, Shiba S, Hojo S, Ando K (2021) Phase 1 study of tazemetostat in Japanese patients with relapsed or refractory B-cell lymphoma. Cancer Sci 112(3):1123–1131. https://doi.org/10.1111/cas.14822

Article  CAS  PubMed  PubMed Central  Google Scholar 

Izutsu K, Ando K, Nishikori M, Shibayama H, Teshima T, Kuroda J, Kato K, Imaizumi Y, Nosaka K, Sakai R, Hojo S, Nakanishi T, Rai S (2021) Phase II study of tazemetostat for relapsed or refractory B-cell non-Hodgkin lymphoma with EZH2 mutation in Japan. Cancer Sci 112(9):3627–3635. https://doi.org/10.1111/cas.15040

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang P, de Gooijer MC, Buil LC, Beijnen JH, Li G, van Tellingen O (2015) ABCB1 and ABCG2 restrict the brain penetration of a panel of novel EZH2-Inhibitors. Int J Cancer J Int du Cancer 137(8):2007–2018. https://doi.org/10.1002/ijc.29566

Article  CAS  Google Scholar 

Budagaga Y, Sabet Z, Zhang Y, Novotna E, Hanke I, Rozkos T, Hofman J (2023) Tazemetostat synergistically combats multidrug resistance by the unique triple inhibition of ABCB1, ABCC1, and ABCG2 efflux transporters in vitro and ex vivo. Biochem Pharmacol 216:115769. https://doi.org/10.1016/j.bcp.2023.115769

Article  CAS  PubMed  Google Scholar