^
    5d
    Computational hybrid framework integrating clinical-mutation profiling and physics-based simulations to predict structural tolerance of Bruton tyrosine kinase (BTK) and sustained ARQ 531 binding. (PubMed, Curr Res Struct Biol)
    Finally, the total binding free energy (TBE) calculations revealed that ARQ531 exhibits broadly conserved binding energetics across clinically observed BTK mutants, with select variants (notably C481 substitutions) showing moderately enhanced stabilization relative to the wild type. These findings confirm that ARQ 531 remains a significant investigational therapy specifically for overcoming drug resistance in multiple leukemias and B-cell malignancies and can serve as a starting point for designing more robust and effective BTK inhibitors.
    Journal
    |
    BTK (Bruton Tyrosine Kinase)
    |
    nemtabrutinib (MK-1026)
    13d
    waveLINE-006: A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-006) (clinicaltrials.gov)
    P2, N=223, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting
    Enrollment closed • Pan tumor
    |
    zilovertamab vedotin (MK-2140) • nemtabrutinib (MK-1026)
    14d
    Nemtabrutinib, Bortezomib, and Rituximab for WM (clinicaltrials.gov)
    P2, N=19, Not yet recruiting, Seoul National University Hospital
    New P2 trial
    |
    Rituxan (rituximab) • bortezomib • nemtabrutinib (MK-1026)
    1m
    A Study of Nemtabrutinib in Participants With Moderate Hepatic Impairment (MK-1026-015) (clinicaltrials.gov)
    P1, N=32, Recruiting, Merck Sharp & Dohme LLC | N=16 --> 32
    Enrollment change
    |
    nemtabrutinib (MK-1026)
    2ms
    Nemtabrutinib and Lisocabtagene Maraleucel for the Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (clinicaltrials.gov)
    P2, N=20, Not yet recruiting, Fred Hutchinson Cancer Center | Initiation date: Dec 2025 --> Apr 2026
    Trial initiation date
    |
    cyclophosphamide • Breyanzi (lisocabtagene maraleucel) • nemtabrutinib (MK-1026)
    3ms
    Nemtabrutinib and Pembrolizumab for the Treatment of Richter Transformation, Diffuse Large B-cell Lymphoma Subtype (clinicaltrials.gov)
    P2, N=32, Recruiting, Roswell Park Cancer Institute | Initiation date: Nov 2025 --> Feb 2026
    Trial initiation date • Tumor mutational burden
    |
    PD-L1 (Programmed death ligand 1)
    |
    Keytruda (pembrolizumab) • nemtabrutinib (MK-1026)
    3ms
    A Study of the Effect of Diltiazem on the Plasma Levels of Nemtabrutinib (MK-1026-022) (clinicaltrials.gov)
    P1, N=24, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting
    Enrollment open
    |
    nemtabrutinib (MK-1026)
    4ms
    BELLWAVE-003: Efficacy and Safety of Nemtabrutinib (MK-1026) in Participants With Hematologic Malignancies (MK-1026-003) (clinicaltrials.gov)
    P2, N=490, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Mar 2027 --> Jan 2029 | Trial primary completion date: Mar 2027 --> Jan 2029
    Trial completion date • Trial primary completion date
    |
    TP53 (Tumor protein P53) • CCND1 (Cyclin D1) • CD4 (CD4 Molecule)
    |
    TP53 mutation • Chr t(11;14)
    |
    nemtabrutinib (MK-1026)
    4ms
    A Study of Nemtabrutinib in Participants With Moderate Hepatic Impairment (MK-1026-015) (clinicaltrials.gov)
    P1, N=16, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Dec 2025 --> Sep 2026 | Trial primary completion date: Dec 2025 --> Sep 2026
    Trial completion date • Trial primary completion date
    |
    nemtabrutinib (MK-1026)
    4ms
    A Study of the Effect of Diltiazem on the Plasma Levels of Nemtabrutinib (MK-1026-022) (clinicaltrials.gov)
    P1, N=24, Not yet recruiting, Merck Sharp & Dohme LLC
    New P1 trial
    |
    nemtabrutinib (MK-1026)
    4ms
    A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010). (clinicaltrials.gov)
    P3, N=735, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Mar 2035 --> Jul 2035 | Trial primary completion date: Mar 2035 --> Jun 2032
    Trial completion date • Trial primary completion date
    |
    TP53 (Tumor protein P53) • BTK (Bruton Tyrosine Kinase) • IGH (Immunoglobulin Heavy Locus)
    |
    TP53 mutation • IGH mutation
    |
    Venclexta (venetoclax) • Rituxan (rituximab) • nemtabrutinib (MK-1026)
    5ms
    Combined cellular and biochemical profiling of Bruton's tyrosine kinase inhibitor nemtabrutinib reveals potential application in MAPK-driven cancers. (PubMed, Front Oncol)
    Molecular docking studies suggest that nemtabrutinib preferentially binds in the ATP-binding pocket of MEK1. Combined cancer cell panel and biochemical profiling reveals previously underappreciated cross-reactivities of nemtabrutinib indicating a potential application in MAPK-driven cancers.
    Journal
    |
    BRAF (B-raf proto-oncogene) • FGFR3 (Fibroblast growth factor receptor 3) • MAP2K1 (Mitogen-activated protein kinase kinase 1)
    |
    BRAF mutation
    |
    nemtabrutinib (MK-1026)