JNJ-4681

P1, N=75, Active, not recruiting, Janssen Research & Development, LLC | Trial primary completion date: Jul 2024 --> Jul 2025

P1, N=85, Active, not recruiting, Janssen Research & Development, LLC | Trial primary completion date: Apr 2025 --> Apr 2026

P1, N=75, Active, not recruiting, Janssen Research & Development, LLC | Phase classification: P1b --> P1

P1b, N=75, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Apr 2026 --> Jul 2025

P1, N=85, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting | Trial completion date: Apr 2025 --> Apr 2026

P1b, N=75, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2024 --> Apr 2026

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.

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.

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.