^
    3ms
    A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov)
    P1, N=75, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Jul 2025 --> Dec 2026
    Trial completion date • Combination therapy
    |
    safimaltib (JNJ-6633) • JNJ-4681
    3ms
    A Study of JNJ-64264681 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov)
    P1, N=85, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Apr 2026 --> Dec 2026
    Trial completion date
    |
    JNJ-4681
    9ms
    A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov)
    P1, N=75, Active, not recruiting, Janssen Research & Development, LLC | Trial primary completion date: Jul 2024 --> Jul 2025
    Trial primary completion date • Combination therapy
    |
    safimaltib (JNJ-6633) • JNJ-4681
    9ms
    A Study of JNJ-64264681 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov)
    P1, N=85, Active, not recruiting, Janssen Research & Development, LLC | Trial primary completion date: Apr 2025 --> Apr 2026
    Trial primary completion date
    |
    JNJ-4681
    11ms
    A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov)
    P1, N=75, Active, not recruiting, Janssen Research & Development, LLC | Phase classification: P1b --> P1
    Phase classification • Combination therapy
    |
    safimaltib (JNJ-6633) • JNJ-4681
    1year
    A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov)
    P1b, N=75, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Apr 2026 --> Jul 2025
    Trial completion date • Combination therapy
    |
    safimaltib (JNJ-6633) • JNJ-4681
    1year
    A Study of JNJ-64264681 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov)
    P1, N=85, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting | Trial completion date: Apr 2025 --> Apr 2026
    Enrollment closed • Trial completion date
    |
    JNJ-4681
    1year
    A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov)
    P1b, N=75, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2024 --> Apr 2026
    Trial completion date • Combination therapy
    |
    safimaltib (JNJ-6633) • JNJ-4681
    over1year
    A Phase 1 First-in-Human Pharmacokinetic and Pharmacodynamic Study of JNJ-64264681, a Covalent Inhibitor of Bruton's Tyrosine Kinase. (PubMed, Clin Pharmacol Drug Dev)
    JNJ-64264681 showed no safety signals of concern. Overall, safety, tolerability, PK, BTKO, and PK/PD modeling guided the rationale for dose selection for the subsequent first-in-patient lymphoma studies.
    P1 data • PK/PD data • Clinical Trial,Phase I • Journal
    |
    JNJ-4681
    over3years
    [VIRTUAL] DISCOVERY AND PRECLINICAL PROPERTIES OF JNJ-64264681, A POTENT AND SELECTIVE COVALENT BTK INHIBITOR FOR THE TREATMENT OF B CELL MALIGNANCIES (EHA 2021)
    BTK inhibitors have been widely studied in B-cell hematologic malignancies and 3 inhibitors, including the first-in-class BTK inhibitor ibrutinib, are currently approved. Conclusion The preclinical results confirm that JNJ-64264681 is a highly selective and potent BTK inhibitor and provide proof-of-concept for human trials in patients with B cell malignancies driven by the classical NF-κB pathway. JNJ-64264681 is currently in human clinical trials (NCT04210219 and NCT04657224) as single agent to establish dose and pharmacokinetics and to evaluate efficacy in combination with the first-in-class MALT1 inhibitor JNJ-67856633.
    Preclinical
    |
    CD79B (CD79b Molecule) • MALT1 (MALT1 Paracaspase)
    |
    CD79B mutation • CD79B mutation
    |
    Imbruvica (ibrutinib) • safimaltib (JNJ-6633) • JNJ-4681
    over3years
    [VIRTUAL] Combination therapy of JNJ-67856633, a novel, first-in-class MALT1 protease inhibitor, and JNJ-64264681, a novel BTK inhibitor, for the treatment of B-cell lymphomas (AACR 2021)
    Taken together, the in vitro and in vivo data for JNJ‑67856633 and JNJ-64264681 suggest that combination therapy can increase the anti-tumor effect of the monotherapies and provide a more sustained response, offering strong support for clinical investigation of the combination of these two novel agents. A phase 1b combination study is scheduled to initiate.
    Combination therapy
    |
    CD79B (CD79b Molecule) • IL2RA (Interleukin 2 receptor, alpha) • CARD11 (Caspase Recruitment Domain Family Member 11) • CD4 (CD4 Molecule) • MALT1 (MALT1 Paracaspase) • FOXP3 (Forkhead Box P3)
    |
    CD79B mutation • CARD11 mutation • CD79B mutation
    |
    safimaltib (JNJ-6633) • JNJ-4681