Study of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (Cohort 1 and Cohort 2)

Summary

The goal of this clinical study is to test how well the study drug, brexucabtagene autoleucel (KTE-X19), works in participants with relapsed/refractory (r/r) mantle cell lymphoma (MCL).

Timeline

Start

2015-11-09

Primary completion

2023-09-22

Completion

2023-09-22

Publications

• Background Michael Wang,1 Javier Munoz,2 Andre Goy,3 Frederick L. Locke,4 Caron A. Jacobson,5 Brian T. Hill,6 John M. Timmerman,7 Houston Holmes,8 Samantha Jaglowski,9 Ian W. Flinn,10 Peter A. McSweeney,11 David B. Miklos,12 John M. Pagel,13 Marie José Kersten,14 Noel Milpied,15 Henry Fung,16 Max S. Topp,17 Roch Houot,18 Amer Beitinjaneh,19 Weimin Peng,20 Lianqing Zheng,20 John M. Rossi,20 Rajul K. Jain,20 Arati V. Rao,20 and Patrick M. Reagan21
• Background Wang M, Munoz J, Goy A, Locke FL, Jacobson CA, Hill BT, Timmerman JM, Holmes H, Jaglowski S, Flinn IW, McSweeney PA,Miklos DB, Pagel JM, Kersten MJ, Peng W,Zheng L,Rossi JM, Jain RK, Rao AV, Reagan PM
• Background Wang, Michael L., MD(1); Munoz, Javier, MD(2); Goy, Andre, MD(3); Locke, Frederick L., MD(4); Jacobson, Caron A., MD, MMSc(5); Hill, Brian T., MD(6); Timmerman, John M., MD(7); Holmes, Houston, MD(8); Jaglowski, Samantha, MD, MPH(9); Flinn, Ian W., MD, PhD(10); McSweeney, Peter A., MD(11); Miklos, David B., MD, PhD(12); Pagel, John M., MD, PhD, DSc(13); Jose Kersten, Marie, MD, PhD(14); Peng, Weimin, MS(15); Zheng, Lianqing, PhD(15); Rossi, John M., MS(15); Jain, Rajul K., MD(15); Rao, Arati V., MD(15); Reagan, Patrick M, MD(16)
• Background Wang, Michael; Lundry Locke, Frederick; Munoz, Javier; Goy, Andre; Eccleston Holmes, Houston; Siddiqi, Tanya; Flinn, Ian; McSweeney, Peter A; Michael Reagan, Patrick; Thomas Hill, Brian; Jacobson, Caron A.; Rizzieri, David A.; Heffner, Leonard T.; Mary Jaglowski, Samantha; Bernard Miklos, David; Shaughnessy, Paul; Unabia, Sherry; Rossi, John M.; Jiang, Yizhou; Jain, Rajul K.
• Background Cheah CY, Chihara D, Romaguera JE, Fowler NH, Seymour JF, Hagemeister FB, Champlin RE, Wang ML. Patients with mantle cell lymphoma failing ibrutinib are unlikely to respond to salvage chemotherapy and have poor outcomes. Ann Oncol. 2015 Jun;26(6):1175-1179. doi: 10.1093/annonc/mdv111. Epub 2015 Feb 23.
• Background Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.
• Background Dreyling M, Jurczak W, Jerkeman M, Silva RS, Rusconi C, Trneny M, Offner F, Caballero D, Joao C, Witzens-Harig M, Hess G, Bence-Bruckler I, Cho SG, Bothos J, Goldberg JD, Enny C, Traina S, Balasubramanian S, Bandyopadhyay N, Sun S, Vermeulen J, Rizo A, Rule S. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Lancet. 2016 Feb 20;387(10020):770-8. doi: 10.1016/S0140-6736(15)00667-4. Epub 2015 Dec 7.
• Background Epperla N, Hamadani M, Cashen AF, Ahn KW, Oak E, Kanate AS, Calzada O, Cohen JB, Farmer L, Ghosh N, Tallarico M, Nabhan C, Costa LJ, Kenkre VP, Hari PN, Fenske TS. Predictive factors and outcomes for ibrutinib therapy in relapsed/refractory mantle cell lymphoma-a "real world" study. Hematol Oncol. 2017 Dec;35(4):528-535. doi: 10.1002/hon.2380. Epub 2017 Jan 8.
• Background Fisher RI, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S, Epner E, Krishnan A, Leonard JP, Lonial S, Stadtmauer EA, O'Connor OA, Shi H, Boral AL, Goy A. Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2006 Oct 20;24(30):4867-74. doi: 10.1200/JCO.2006.07.9665. Epub 2006 Sep 25.
• Background Goy A, Sinha R, Williams ME, Kalayoglu Besisik S, Drach J, Ramchandren R, Zhang L, Cicero S, Fu T, Witzig TE. Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: phase II MCL-001 (EMERGE) study. J Clin Oncol. 2013 Oct 10;31(29):3688-95. doi: 10.1200/JCO.2013.49.2835. Epub 2013 Sep 3.
• Background Jain P, Kanagal-Shamanna R, Zhang S, Ahmed M, Ghorab A, Zhang L, Ok CY, Li S, Hagemeister F, Zeng D, Gong T, Chen W, Badillo M, Nomie K, Fayad L, Medeiros LJ, Neelapu S, Fowler N, Romaguera J, Champlin R, Wang L, Wang ML. Long-term outcomes and mutation profiling of patients with mantle cell lymphoma (MCL) who discontinued ibrutinib. Br J Haematol. 2018 Nov;183(4):578-587. doi: 10.1111/bjh.15567. Epub 2018 Sep 2.
• Background Kratz A, Ferraro M, Sluss PM, Lewandrowski KB. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Laboratory reference values. N Engl J Med. 2004 Oct 7;351(15):1548-63. doi: 10.1056/NEJMcpc049016. No abstract available.
• Background Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, Grupp SA, Mackall CL. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014 Jul 10;124(2):188-95. doi: 10.1182/blood-2014-05-552729. Epub 2014 May 29.
• Background Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy A, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Wiezorek JS, Navale L, Xue A, Jiang Y, Bot A, Rossi JM, Kim JJ, Go WY, Neelapu SS. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019 Jan;20(1):31-42. doi: 10.1016/S1470-2045(18)30864-7. Epub 2018 Dec 2.
• Background Martin P, Maddocks K, Leonard JP, Ruan J, Goy A, Wagner-Johnston N, Rule S, Advani R, Iberri D, Phillips T, Spurgeon S, Kozin E, Noto K, Chen Z, Jurczak W, Auer R, Chmielowska E, Stilgenbauer S, Bloehdorn J, Portell C, Williams ME, Dreyling M, Barr PM, Chen-Kiang S, DiLiberto M, Furman RR, Blum KA. Postibrutinib outcomes in patients with mantle cell lymphoma. Blood. 2016 Mar 24;127(12):1559-63. doi: 10.1182/blood-2015-10-673145. Epub 2016 Jan 13.
• Background Rule S, Dreyling M, Goy A, Hess G, Auer R, Kahl B, Cavazos N, Liu B, Yang S, Clow F, Goldberg JD, Beaupre D, Vermeulen J, Wildgust M, Wang M. Outcomes in 370 patients with mantle cell lymphoma treated with ibrutinib: a pooled analysis from three open-label studies. Br J Haematol. 2017 Nov;179(3):430-438. doi: 10.1111/bjh.14870. Epub 2017 Aug 18.
• Background Rule S, Dreyling M, Goy A, Hess G, Auer R, Kahl B, Hernandez-Rivas JA, Qi K, Deshpande S, Parisi L, Wang M. Ibrutinib for the treatment of relapsed/refractory mantle cell lymphoma: extended 3.5-year follow up from a pooled analysis. Haematologica. 2019 May;104(5):e211-e214. doi: 10.3324/haematol.2018.205229. Epub 2018 Nov 15. No abstract available.
• Background Topp MS, Gokbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, Dombret H, Fielding AK, Heffner L, Larson RA, Neumann S, Foa R, Litzow M, Ribera JM, Rambaldi A, Schiller G, Bruggemann M, Horst HA, Holland C, Jia C, Maniar T, Huber B, Nagorsen D, Forman SJ, Kantarjian HM. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015 Jan;16(1):57-66. doi: 10.1016/S1470-2045(14)71170-2. Epub 2014 Dec 16.
• Background Wang M, Schuster SJ, Phillips T, Lossos IS, Goy A, Rule S, Hamadani M, Ghosh N, Reeder CB, Barnett E, Bravo MC, Martin P. Observational study of lenalidomide in patients with mantle cell lymphoma who relapsed/progressed after or were refractory/intolerant to ibrutinib (MCL-004). J Hematol Oncol. 2017 Nov 2;10(1):171. doi: 10.1186/s13045-017-0537-5.
• Background Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH, Romaguera JE, Williams ME, Barrientos JC, Chmielowska E, Radford J, Stilgenbauer S, Dreyling M, Jedrzejczak WW, Johnson P, Spurgeon SE, Li L, Zhang L, Newberry K, Ou Z, Cheng N, Fang B, McGreivy J, Clow F, Buggy JJ, Chang BY, Beaupre DM, Kunkel LA, Blum KA. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013 Aug 8;369(6):507-16. doi: 10.1056/NEJMoa1306220. Epub 2013 Jun 19.
• Munoz J, Locke FL, Reagan PM, Goy A, Jacobson CA, Hill BT, Timmerman JM, Flinn IW, Miklos DB, Pagel JM, Kersten MJ, Forcade E, Topp MS, Houot R, Beitinjaneh A, Zheng D, Chang M, Zhang W, Shen RR, Khalid RD, Kloos I, Wang ML. Five-year follow-up of patients with relapsed/refractory mantle cell lymphoma treated with anti-CD19 CAR T-cell therapy in ZUMA-2, Cohorts 1 and 2. J Hematol Oncol. 2026 Apr 27;19(1):39. doi: 10.1186/s13045-026-01797-4.
• Darnell EP, Gallagher KME, Kanska J, Scarfo I, Balderrama-Gutierrez G, Berger TR, Budka J, Bozym DJ, Huang T, Shen R, Leick MB, Maus MV. Ibrutinib exposure correlates with improved efficacy of CAR T cells in patients with mantle cell lymphoma. Blood Adv. 2026 Feb 24;10(4):1023-1034. doi: 10.1182/bloodadvances.2025018137.
• van Meerten T, Kersten MJ, Iacoboni G, Hess G, Mutsaers P, Garcia-Sancho AM, Goy A, Gine E, Hill BT, Weng WK, Reagan PM, Patel K, Galal A, Herbaux C, Sanderson R, Forcade E, Topp MS, Houot R, Zheng D, Zhang W, Kanska J, Shen RR, Damico Khalid R, Kloos I, Dreyling M, Wang ML. Brexucabtagene autoleucel for BTKi-naive relapsed/refractory mantle cell lymphoma: primary analysis of ZUMA-2 cohort 3. Blood. 2026 Mar 19;147(12):1302-1314. doi: 10.1182/blood.2025029734.
• Wang M, Munoz J, Goy A, Locke FL, Jacobson CA, Hill BT, Timmerman JM, Holmes H, Jaglowski S, Flinn IW, McSweeney PA, Miklos DB, Pagel JM, Kersten MJ, Bouabdallah K, Khanal R, Topp MS, Houot R, Beitinjaneh A, Peng W, Fang X, Shen RR, Siddiqi R, Kloos I, Reagan PM. Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study. J Clin Oncol. 2023 Jan 20;41(3):555-567. doi: 10.1200/JCO.21.02370. Epub 2022 Jun 4.
• Wang M, Jain P, Chi TL, Chen SE, Heimberger A, Weathers SP, Zheng L, Rao AV, Rossi JM. Management of a patient with mantle cell lymphoma who developed severe neurotoxicity after chimeric antigen receptor T-cell therapy in ZUMA-2. J Immunother Cancer. 2020 Oct;8(2):e001114. doi: 10.1136/jitc-2020-001114.
• Wang M, Munoz J, Goy A, Locke FL, Jacobson CA, Hill BT, Timmerman JM, Holmes H, Jaglowski S, Flinn IW, McSweeney PA, Miklos DB, Pagel JM, Kersten MJ, Milpied N, Fung H, Topp MS, Houot R, Beitinjaneh A, Peng W, Zheng L, Rossi JM, Jain RK, Rao AV, Reagan PM. KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma. N Engl J Med. 2020 Apr 2;382(14):1331-1342. doi: 10.1056/NEJMoa1914347.

Drugs

Indications