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Leukemia & Lymphoma Volume 65, 2024 - Issue 4
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Original Articles

Results from phase 1 of the MANIFEST clinical trial to evaluate the safety and tolerability of pelabresib in patients with myeloid malignancies

Eytan M. Steina Memorial Sloan Kettering Cancer Center, New York, NY, USACorrespondence[email protected]
View further author information
,
Amir T. Fathib Leukemia Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USAView further author information
,
Wael A. Harbc Horizon Oncology and Research Center, Lafayette, IN, USAView further author information
,
Gozde Colakd Constellation Pharmaceuticals, Inc., a MorphoSys Company, Boston, MA, USAView further author information
,
Andrea Fuscod Constellation Pharmaceuticals, Inc., a MorphoSys Company, Boston, MA, USAView further author information
&
James K. Mangane Department of Medicine, Division of Blood and Marrow Transplantation, University of California San Diego, La Jolla, CA, USAView further author information
Pages 503-510 | Received 26 Sep 2023, Accepted 26 Dec 2023, Published online: 23 Jan 2024

References

  • Filippakopoulos P, Knapp S. Targeting bromodomains: epigenetic readers of lysine acetylation. Nat Rev Drug Discov. 2014;13(5):337–356. doi:10.1038/nrd4286
  • Shi J, Vakoc CR. The mechanisms behind the therapeutic activity of BET bromodomain inhibition. Mol Cell. 2014;54(5):728–736. doi:10.1016/j.molcel.2014.05.016
  • Ceribelli M, Kelly PN, Shaffer AL, et al. Blockade of oncogenic IκB kinase activity in diffuse large B-cell lymphoma by bromodomain and extraterminal domain protein inhibitors. Proc Natl Acad Sci USA. 2014;111(31):11365–11370. doi:10.1073/pnas.1411701111
  • Pemmaraju N, Verstovsek S, Mesa R, et al. Defining disease modification in myelofibrosis in the era of targeted therapy. Cancer. 2022;128(13):2420–2432. doi:10.1002/cncr.34205
  • Naymagon L, Mascarenhas J. Myelofibrosis-related anemia: current and emerging therapeutic strategies. Hemasphere. 2017;1(1):e1. doi:10.1097/HS9.0000000000000001
  • Di Francesco B, Verzella D, Capece D, et al. NF-κB: a druggable target in acute myeloid leukemia. Cancers (Basel). 2022;14(14):3557. doi:10.3390/cancers14143557
  • Braun T, Carvalho G, Fabre C, et al. Targeting NF-kappaB in hematologic malignancies. Cell Death Differ. 2006;13(5):748–758. doi:10.1038/sj.cdd.4401874
  • Albrecht BK, Gehling VS, Hewitt MC, et al. Identification of a benzoisoxazoloazepine inhibitor (CPI-0610) of the bromodomain and extra-terminal (BET) family as a candidate for human clinical trials. J Med Chem. 2016;59(4):1330–1339. doi:10.1021/acs.jmedchem.5b01882
  • Zhang L, Cai T, Lin X, et al. Selective inhibition of the second bromodomain of BET family proteins results in robust antitumor activity in preclinical models of acute myeloid leukemia. Mol Cancer Ther. 2021;20(10):1809–1819. doi:10.1158/1535-7163.MCT-21-0029
  • Mascarenhas J, Kremyanskaya M, Patriarca A, et al. MANIFEST: pelabresib in combination with ruxolitinib for Janus kinase inhibitor treatment-naïve myelofibrosis. J Clin Oncol. 2023;41(32):4993–5004. doi:10.1200/JCO.22.01972.
  • Tremblay D, Mascarenhas J. Next generation therapeutics for the treatment of myelofibrosis. Cells. 2021;10(5):1034. doi:10.3390/cells10051034
  • Mims AS, Solh M, Saultz JN, et al. Final results of a phase 1b study of BET inhibitor PLX2853 in patients with relapsed or refractory acute myeloid leukemia or high risk myelodysplastic syndrome. Blood. 2021;138(1):3420–3420. doi:10.1182/blood-2021-152040
  • Borthakur G, Odenike O, Aldoss I, et al. A phase 1 study of the pan-bromodomain and extraterminal inhibitor mivebresib (ABBV-075) alone or in combination with venetoclax in patients with relapsed/refractory acute myeloid leukemia. Cancer. 2021;127(16):2943–2953. doi:10.1002/cncr.33590
  • Blum KA, Supko JG, Maris MB, et al. A phase I study of pelabresib (CPI-0610), a small-molecule inhibitor of BET proteins, in patients with relapsed or refractory lymphoma. Cancer Res Commun. 2022;2(8):795–805. doi:10.1158/2767-9764.CRC-22-0060
  • Keller P, Cui J, Mertz J, et al. BET inhibitor pelabresib decreases inflammatory cytokines, improves bone marrow fibrosis and function, and demonstrates clinical response irrespective of mutation status in myelofibrosis patients. Presented at the European Hematology Association; June 9–17, 2021; virtual congress.
  • Kuendgen A, Kasprzak A, Germing U. Hybrid or mixed myelodysplastic/myeloproliferative disorders - epidemiological features and overview. Front Oncol. 2021;11:778741. doi:10.3389/fonc.2021.778741
  • ClinicalTrials.gov. A phase 2 study of CPI-0610 with and without ruxolitinib in patients with myelofibrosis. NCT02158858. 2022. Available from: https://clinicaltrials.gov/study/NCT02158858
  • Falchook G, Rosen S, LoRusso P, et al. Development of 2 bromodomain and extraterminal inhibitors with distinct pharmacokinetic and pharmacodynamic profiles for the treatment of advanced malignancies. Clin Cancer Res. 2020;26(6):1247–1257. doi:10.1158/1078-0432.CCR-18-4071
  • Lewin J, Soria JC, Stathis A, et al. Phase Ib trial with birabresib, a small-molecule inhibitor of bromodomain and extraterminal proteins, in patients with selected advanced solid tumors. J Clin Oncol. 2018;36(30):3007–3014. doi:10.1200/JCO.2018.78.2292
  • Shapiro GI, LoRusso P, Dowlati A, et al. A phase 1 study of RO6870810, a novel bromodomain and extra-terminal protein inhibitor, in patients with NUT carcinoma, other solid tumours, or diffuse large B-cell lymphoma. Br J Cancer. 2021;124(4):744–753. doi:10.1038/s41416-020-01180-1
  • ClinicalTrials.gov. Phase 3 study of pelabresib (CPI-0610) in myelofibrosis (MF) (MANIFEST-2). NCT04603495. 2022. Available from: https://clinicaltrials.gov/study/NCT04603495

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