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    14d
    Pharmacokinetics and Safety Study of Pelabresib in Patients With Advanced Malignancies and Hepatic Impairment (clinicaltrials.gov)
    P1, N=24, Not yet recruiting, Novartis Pharmaceuticals
    New P1 trial
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    pelabresib (DAK539)
    1m
    Progress of investigational bromodomain and extra-terminal domain inhibitors for myelofibrosis therapy. (PubMed, Expert Opin Investig Drugs)
    Trials assessing the efficacy of pelabresib, ABBV-744, INCB057643, BMS-986158, and OPN-2853 are detailed herein. Research into novel pan-and selective-BETis both as monotherapy and in combination with JAKis or other mechanism-based therapies are ongoing. Whether BETi therapy in MF will ultimately deliver substantial anti-clonal activity to modify disease biology and meaningfully impact clinical outcomes is yet to be determined.
    Review • Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    ABBV-744 • INCB057643 • pelabresib (DAK539) • ezobresib (BMS-986158) • zavabresib (OPN-2853)
    1m
    MANIFEST-3: A Phase 3 Study of Pelabresib (DAK539) and Ruxolitinib in Myelofibrosis (MF) (clinicaltrials.gov)
    P3, N=460, Not yet recruiting, Novartis Pharmaceuticals
    New P3 trial
    |
    Jakafi (ruxolitinib) • pelabresib (DAK539)
    2ms
    Study of Pelabresib add-on to Ruxolitinib in Japanese Adult Patients With Myelofibrosis (clinicaltrials.gov)
    P1, N=3, Not yet recruiting, Novartis Pharmaceuticals
    New P1 trial
    |
    Jakafi (ruxolitinib) • pelabresib (DAK539)
    2ms
    A Drug-drug Interaction Study to Evaluate the Effects of Pelabresib on the Pharmacokinetics of Repaglinide, Midazolam, and Combined Oral Contraceptive in Patients With Advanced Malignancies (clinicaltrials.gov)
    P1, N=24, Not yet recruiting, Novartis Pharmaceuticals
    New P1 trial
    |
    pelabresib (DAK539)
    3ms
    Phase 3 Study of Pelabresib (CPI-0610) in Myelofibrosis (MF) (MANIFEST-2) (clinicaltrials.gov)
    P3, N=430, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2027 --> Jun 2027
    Trial completion date
    |
    Jakafi (ruxolitinib) • pelabresib (DAK539)
    8ms
    Highlights from MPN Asia 2025: Advances in Molecular Pathogenesis and Therapeutic Strategies in Myeloproliferative Neoplasms. (PubMed, Curr Hematol Malig Rep)
    Ropeginterferon alfa-2b, a novel interferon-based therapy, demonstrated durable clinical efficacy in polycythemia vera...Combination regimens involving ruxolitinib and agents such as pelabresib, selinexor, and interferon showed potential for enhanced efficacy...Its early use and personalized strategies are increasingly recognized. Real-world data and regional insights are shaping a more nuanced, globally informed approach to MPN care.
    Review • Journal
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    ASXL1 (ASXL Transcriptional Regulator 1) • IL17A (Interleukin 17A)
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    TP53 mutation • ASXL1 mutation
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    Jakafi (ruxolitinib) • Xpovio (selinexor) • pelabresib (DAK539) • Besremi (ropeginterferon alfa-2b-njft)
    8ms
    An Extension Study for Patients Previously Enrolled in Studies With Pelabresib (clinicaltrials.gov)
    P3, N=50, Recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2029 --> Jun 2027 | Trial primary completion date: Jun 2029 --> Jun 2027
    Trial completion date • Trial primary completion date
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    pelabresib (DAK539)
    1year
    MANIFEST: A Phase 2 Study of CPI-0610 with and Without Ruxolitinib in Patients with Myelofibrosis (clinicaltrials.gov)
    P1/2, N=336, Completed, Constellation Pharmaceuticals | Active, not recruiting --> Completed
    Trial completion
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    Jakafi (ruxolitinib) • hydroxyurea • pelabresib (DAK539)
    over1year
    Preclinical efficacy of CDK7 inhibitor-based combinations against myeloproliferative neoplasms transformed to AML. (PubMed, Blood)
    Co-treatment with SY-5609 and ruxolitinib was synergistically lethal in HEL, SET2 and PD post-MPN-sAML cells.  A CRISPR screen in SET2 and HEL cells revealed BRD4, CBP and p300 as co-dependencies with SY-5609 treatment. Accordingly, co-treatment with SY-5609 and the BETi OTX015 or pelabresib or with the CBP/p300 inhibitor GNE-049 was synergistically lethal in MPN-sAML cells (including those exhibiting TP53 loss). Finally, in the HEL-Luc/GFP xenograft model, compared to each agent alone, co-treatment with SY-5609 and OTX015 reduced post-MPN-sAML burden and improved survival without inducing host toxicity. These findings demonstrate promising preclinical activity of the CDK7i-based combinations with BETi or HATi against advanced-MPNs, including post-MPN-sAML.
    Preclinical • Journal
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    TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • BCL2L1 (BCL2-like 1) • CDK6 (Cyclin-dependent kinase 6) • CASP3 (Caspase 3) • PIM1 (Pim-1 Proto-Oncogene) • ITGAM (Integrin, alpha M) • BRD4 (Bromodomain Containing 4) • CASP9 (Caspase 9) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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    MYC expression • CCND1 expression
    |
    Jakafi (ruxolitinib) • birabresib (OTX015) • SY-5609 • pelabresib (DAK539)
    over1year
    An Extension Study for Patients Previously Enrolled in Studies with Pelabresib (clinicaltrials.gov)
    P3, N=50, Recruiting, Constellation Pharmaceuticals | Not yet recruiting --> Recruiting | Trial completion date: Jun 2024 --> Jun 2029 | Trial primary completion date: Jun 2024 --> Jun 2029
    Enrollment open • Trial completion date • Trial primary completion date
    |
    pelabresib (DAK539)
    almost2years
    An Extension Study for Patients Previously Enrolled in Studies With Pelabresib (clinicaltrials.gov)
    P3, N=50, Not yet recruiting, Constellation Pharmaceuticals
    New P3 trial
    |
    pelabresib (DAK539)