Phase III MANIFEST-2: Pelabresib + ruxolitinib vs placebo + ruxolitinib in JAK inhibitor treatment-naive myelofibrosis Review


Authors: Harrison, C. N.; Gupta, V. K.; Gerds, A. T.; Rampal, R.; Verstovsek, S.; Talpaz, M.; Kiladjian, J. J.; Mesa, R.; Kuykendall, A. T.; Vannucchi, A. M.; Palandri, F.; Grosicki, S.; Devos, T.; Jourdan, E.; Wondergem, M. J.; Al-Ali, H. K.; Buxhofer-Ausch, V.; Alvarez-Larrán, A.; Patriarca, A.; Kremyanskaya, M.; Mead, A. J.; Akhani, S.; Sheikine, Y.; Colak, G.; Mascarenhas, J.
Review Title: Phase III MANIFEST-2: Pelabresib + ruxolitinib vs placebo + ruxolitinib in JAK inhibitor treatment-naive myelofibrosis
Abstract: Myelofibrosis (MF) is a clonal myeloproliferative neoplasm, typically associated with disease-related symptoms, splenomegaly, cytopenias and bone marrow fibrosis. Patients experience a significant symptom burden and a reduced life expectancy. Patients with MF receive ruxolitinib as the current standard of care, but the depth and durability of responses and the percentage of patients achieving clinical outcome measures are limited; thus, a significant unmet medical need exists. Pelabresib is an investigational small-molecule bromodomain and extraterminal domain inhibitor currently in clinical development for MF. The aim of this article is to describe the design of the ongoing, global, phase III, double-blind, placebo-controlled MANIFEST-2 study evaluating the efficacy and safety of pelabresib and ruxolitinib versus placebo and ruxolitinib in patients with JAKi treatment-naive MF. Clinical Trial Registration: NCT04603495 (ClinicalTrials.gov). Myelofibrosis (MF) is a rare type of blood cancer that interferes with the process of blood cell production by the bone marrow. In patients with MF, the bone marrow becomes overactive, leading to scarring and subsequently a lack of healthy blood cells being produced. The main symptoms of MF include anemia, fatigue, weakness and pain or discomfort in the abdomen. MF is associated with a shortened life expectancy. The current go-to treatment for MF is ruxolitinib. However, ruxolitinib has shown limited efficacy in improving clinical symptoms long term; so, new safe and effective treatments are needed. Pelabresib is a novel drug currently in clinical development for treating MF. The aim of this article is to describe the design of the ongoing, global phase III MANIFEST-2 study. MANIFEST-2 is evaluating the efficacy and safety of pelabresib and ruxolitinib versus placebo and ruxolitinib in patients with MF.
Keywords: treatment outcome; myelofibrosis; janus kinase inhibitor; myeloid metaplasia; primary myelofibrosis; antineoplastic agents; antineoplastic agent; randomized controlled trials as topic; pyrimidines; pyrazole derivative; pyrazoles; pyrimidine derivative; nitriles; nitrile; randomized controlled trial (topic); complication; ruxolitinib; humans; human; pelabresib; cpi-0610; jaki treatment-naive; manifest-2; janus kinase inhibitors
Journal Title: Future Oncology
Volume: 18
Issue: 27
ISSN: 1479-6694
Publisher: Future Medicine  
Date Published: 2022-09-01
Start Page: 2987
End Page: 2997
Language: English
DOI: 10.2217/fon-2022-0484
PUBMED: 35950489
PROVIDER: scopus
DOI/URL:
Notes: Review -- Export Date: 1 November 2022 -- Source: Scopus
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  1. Raajit Kumar Rampal
    339 Rampal