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    DRUG:

    bleximenib (JNJ-6617)

    i
    Other names: JNJ-6617, JNJ 75276617, JNJ75276617, JNJ-75276617, JNJ6617, JNJ 6617
    Company:
    J&J
    Drug class:
    MLL1 inhibitor
    26d
    CR109124: A Study of Bleximenib in Combination With Acute Myeloid Leukemia (AML) Directed Therapies (clinicaltrials.gov)
    P1, N=200, Recruiting, Janssen Research & Development, LLC | N=150 --> 200
    Enrollment change • Combination therapy
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    Venclexta (venetoclax) • cytarabine • azacitidine • daunorubicin • idarubicin hydrochloride • bleximenib (JNJ-6617)
    3ms
    A Study of JNJ-75276617 in Combination With Conventional Chemotherapy for Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias (clinicaltrials.gov)
    P1, N=0, Withdrawn, Janssen Research & Development, LLC | N=80 --> 0 | Not yet recruiting --> Withdrawn
    Enrollment change • Trial withdrawal • Combination therapy
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • NUP214 (Nucleoporin 214)
    |
    cytarabine • vincristine • Oncaspar liquid (pegaspargase) • fludarabine IV • bleximenib (JNJ-6617)
    4ms
    CR109124: A Study of Bleximenib in Combination With Acute Myeloid Leukemia (AML) Directed Therapies (clinicaltrials.gov)
    P1, N=150, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: May 2024 --> Mar 2025
    Trial primary completion date • Combination therapy
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    Venclexta (venetoclax) • cytarabine • azacitidine • daunorubicin • idarubicin hydrochloride • bleximenib (JNJ-6617)
    4ms
    CR108998: A Phase 1/2 Study of Bleximenib in Participants With Acute Leukemia (clinicaltrials.gov)
    P1/2, N=350, Recruiting, Janssen Research & Development, LLC | N=150 --> 350 | Trial completion date: Feb 2026 --> Oct 2027
    Enrollment change • Trial completion date
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    bleximenib (JNJ-6617)
    5ms
    Preclinical efficacy of potent and selective menin-KMT2A inhibitor JNJ-75276617 in KMT2A- and NPM1-altered leukemias. (PubMed, Blood)
    JNJ-75276617 demonstrated synergistic effects with gilteritinib in vitro in AML cells harboring KMT2A-r. JNJ-75276617 further exhibited synergistic effects with venetoclax and azacitidine in AML cells bearing KMT2A-r in vitro, and significantly increased survival in mice...A co-crystal structure of menin in complex with JNJ-75276617 indicates a unique binding mode distinct from other menin-KMT2A inhibitors, including revumenib. JNJ-75276617 is being clinically investigated for acute leukemias harboring KMT2A or NPM1 alterations, as a monotherapy for relapsed/refractory (R/R) acute leukemia (NCT04811560), or in combination with AML-directed therapies (NCT05453903).
    Preclinical • Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • MEIS1 (Meis Homeobox 1)
    |
    Venclexta (venetoclax) • Xospata (gilteritinib) • azacitidine • Revuforj (revumenib) • bleximenib (JNJ-6617)
    8ms
    CR108998: A Study of JNJ-75276617 in Participants With Acute Leukemia (clinicaltrials.gov)
    P1/2, N=150, Recruiting, Janssen Research & Development, LLC | Phase classification: P1 --> P1/2
    Phase classification
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    bleximenib (JNJ-6617)
    9ms
    CR108998: A Study of JNJ-75276617 in Participants With Acute Leukemia (clinicaltrials.gov)
    P1, N=150, Recruiting, Janssen Research & Development, LLC | N=110 --> 150
    Enrollment change
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    bleximenib (JNJ-6617)
    12ms
    A Study of JNJ-75276617 in Combination With Acute Myeloid Leukemia (AML) Directed Therapies (clinicaltrials.gov)
    P1, N=150, Recruiting, Janssen Research & Development, LLC | Phase classification: P1b --> P1
    Phase classification • Combination therapy
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    Venclexta (venetoclax) • cytarabine • azacitidine • daunorubicin • idarubicin hydrochloride • bleximenib (JNJ-6617)
    12ms
    A Study of JNJ-75276617 in Combination With Conventional Chemotherapy for Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias (clinicaltrials.gov)
    P1, N=80, Not yet recruiting, Janssen Research & Development, LLC | Trial completion date: Sep 2026 --> Jan 2030
    Trial completion date • Combination therapy
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • NUP214 (Nucleoporin 214)
    |
    cytarabine • vincristine • Oncaspar liquid (pegaspargase) • fludarabine IV • bleximenib (JNJ-6617)
    1year
    A Study of JNJ-75276617 in Participants With Acute Leukemia (clinicaltrials.gov)
    P1, N=110, Recruiting, Janssen Research & Development, LLC | Trial completion date: Jun 2025 --> Oct 2025
    Trial completion date
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    bleximenib (JNJ-6617)
    1year
    Preclinical Efficacy of the Menin-KMT2A Inhibitor JNJ-75276617 in Combination with Venetoclax and Azacitidine in AML (ASH 2023)
    Hypomethylating agents (e.g. azacitidine, decitabine) in combination with venetoclax have significantly improved clinical outcomes for AML patients and have become a preferred frontline treatment for AML patients ≥75 years of age, or who have comorbidities that preclude use of intensive induction chemotherapy. These studies suggest that the doublet combinations of either JNJ-75276617 plus venetoclax or azacitidine, or the triplet combination could potentially provide a beneficial treatment option for KMT2A- or NPM1-altered AML, and support the recently initiated clinical trial investigating JNJ-75276617 in combination with AML-directed therapies, including venetoclax and azacitidine (NCT05453903). JNJ-75276617 is also being clinically investigated as a monotherapy for R/R acute leukemia (NCT04811560).
    Preclinical • Combination therapy
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • MEIS1 (Meis Homeobox 1)
    |
    Venclexta (venetoclax) • azacitidine • decitabine • bleximenib (JNJ-6617)
    1year
    A First-in-Human Phase 1 Study of the Menin-KMT2A (MLL1) Inhibitor JNJ-75276617 in Adult Patients with Relapsed/Refractory Acute Leukemia Harboring KMT2A or NPM1 Alterations (ASH 2023)
    Dose escalation in 75276617ALE1001 is ongoing with the RP2D(s) yet to be determined. Pts in dose expansion will receive JNJ-75276617 at the identified RP2D(s). Preliminary results of this FIH Phase 1 study demonstrate that JNJ-75276617 monotherapy has an acceptable safety profile, encouraging antileukemic activity, and emerging biologic activity consistent with the proposed mechanism of action in pts with R/R acute leukemia harboring KMT2A or NPM1 alterations.
    Clinical • P1 data
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • HOXA9 (Homeobox A9) • ITGAM (Integrin, alpha M) • MEIS1 (Meis Homeobox 1)
    |
    NPM1 mutation • MLL rearrangement
    |
    bleximenib (JNJ-6617)
    over1year
    Targeting the undruggable: menin inhibitors ante portas. (PubMed, J Cancer Res Clin Oncol)
    To date at least six different menin-MLL inhibitors are undergoing clinical evaluation as first- and second-line monotherapy in acute leukaemias: DS-1594, BMF-219, JNJ-75276617, DSP-5336, revumenib, and ziftomenib, however, only for revumenib and ziftomenib early clinical data have been reported. The clinical development of novel menin-MLL inhibitors is well in line with the currently ongoing paradigm shift towards targeted therapies seen in the AML treatment landscape. Moreover, the clinical assessment of combinations of these inhibitors with established therapy options in AML could be the fuel for an improved outcome of MLL/NPM1 patients.
    Review • Journal
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • MEIS1 (Meis Homeobox 1)
    |
    NPM1 mutation • MLL rearrangement • MLL rearrangement • KMT2A expression • MLL fusion
    |
    Revuforj (revumenib) • ziftomenib (KO-539) • icovamenib (BMF-219) • bleximenib (JNJ-6617) • emilumenib succinate (DS-1594) • enzomenib (DSP-5336)
    over1year
    A Study of JNJ-75276617 in Participants With Acute Leukemia (clinicaltrials.gov)
    P1, N=110, Recruiting, Janssen Research & Development, LLC | Trial completion date: Jun 2026 --> Jun 2025
    Trial completion date
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    bleximenib (JNJ-6617)
    almost2years
    A Study of JNJ-75276617 in Participants With Acute Leukemia (clinicaltrials.gov)
    P1, N=110, Recruiting, Janssen Research & Development, LLC | Trial completion date: Jun 2025 --> Jun 2026
    Trial completion date
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    bleximenib (JNJ-6617)
    almost2years
    A Phase I/Ib Study of JNJ-75276617 in Pediatric and Young Adult Participants with Relapsed/Refractory Acute Leukemias Estudio fase I/Ib de JNJ-75276617 en sujetos pediátricos y adultos jóvenes con leucemias agudas en recaída o refractarias (clinicaltrialsregister.eu)
    P1, N=80, Ongoing, Janssen-Cilag International NV
    New P1 trial • Combination therapy
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • HOXA9 (Homeobox A9) • NUP214 (Nucleoporin 214) • MEIS1 (Meis Homeobox 1)
    |
    bleximenib (JNJ-6617)
    almost2years
    A Study of JNJ-75276617 in Combination With Conventional Chemotherapy for Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias (clinicaltrials.gov)
    P1, N=80, Not yet recruiting, Janssen Research & Development, LLC | Initiation date: Dec 2022 --> Feb 2024
    Trial initiation date • Combination therapy
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • NUP214 (Nucleoporin 214)
    |
    cytarabine • vincristine • Oncaspar liquid (pegaspargase) • fludarabine IV • bleximenib (JNJ-6617)
    2years
    A Study of JNJ-75276617 in Combination With Acute Myeloid Leukemia (AML) Directed Therapies (clinicaltrials.gov)
    P1b, N=150, Recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2024 --> Jan 2026
    Trial completion date • Combination therapy
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    Venclexta (venetoclax) • azacitidine • bleximenib (JNJ-6617)
    2years
    A Study of JNJ-75276617 in Combination With Conventional Chemotherapy for Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias (clinicaltrials.gov)
    P1, N=80, Not yet recruiting, Janssen Research & Development, LLC
    New P1 trial • Combination therapy
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • NUP214 (Nucleoporin 214)
    |
    cytarabine • vincristine • Oncaspar liquid (pegaspargase) • fludarabine IV • bleximenib (JNJ-6617)
    over2years
    A Study of JNJ-75276617 in Participants With Acute Leukemia (clinicaltrials.gov)
    P1, N=110, Recruiting, Janssen Research & Development, LLC | Trial completion date: Aug 2024 --> Jun 2025
    Trial completion date
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    bleximenib (JNJ-6617)
    over2years
    A Study of JNJ-75276617 in Combination With Acute Myeloid Leukemia (AML) Directed Therapies (clinicaltrials.gov)
    P1b, N=150, Recruiting, Janssen Research & Development, LLC | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    Venclexta (venetoclax) • azacitidine • bleximenib (JNJ-6617)
    over2years
    A Study of JNJ-75276617 in Combination With Acute Myeloid Leukemia (AML) Directed Therapies (clinicaltrials.gov)
    P1b, N=150, Not yet recruiting, Janssen Research & Development, LLC
    New P1 trial • Combination therapy
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    Venclexta (venetoclax) • azacitidine • bleximenib (JNJ-6617)
    over2years
    A Study of JNJ-75276617 in Participants With Acute Leukemia (clinicaltrials.gov)
    P1, N=110, Recruiting, Janssen Research & Development, LLC | Trial completion date: Apr 2024 --> Aug 2024
    Trial completion date
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    bleximenib (JNJ-6617)
    3years
    A Study of JNJ-75276617 in Participants With Acute Leukemia (clinicaltrials.gov)
    P1, N=110, Recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2024 --> Apr 2024
    Trial completion date
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    bleximenib (JNJ-6617)