NCT04876092

A Study of the MALT1 Inhibitor JNJ-67856633 and Ibrutinib in Combination in B-cell NHL and CLL

Completed Phase 1 Last updated 21 August 2025

What this trial tests

Phase 1 trial testing JNJ-67856633 in Leukemia, Lymphocytic, Chronic, B-Cell in 45 participants. Completed in 13 February 2025.

Timeline

28 July 2021

Primary endpoint
13 February 2025

13 February 2025

Quick facts

Lead sponsor	Janssen Research & Development, LLC
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	45
Start date	28 July 2021
Primary completion	13 February 2025
Estimated completion	13 February 2025
Sites	10 locations across Denmark, France, Poland, Sweden

Drugs / interventions tested

• JNJ-67856633 — full drug profile →
• Ibrutinib (ibrutinib) — full drug profile →

Conditions studied

• Leukemia, Lymphocytic, Chronic, B-Cell — all drugs for Leukemia, Lymphocytic, Chronic, B-Cell →
• Lymphoma, Non-Hodgkin — all drugs for Lymphoma, Non-Hodgkin →

Sponsor

Janssen Research & Development, LLC — full company profile →

Who can join

18 and older, any sex, with Leukemia, Lymphocytic, Chronic, B-Cell or Lymphoma, Non-Hodgkin. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The purpose of this study is to determine the safety and recommended Phase 2 dose (RP2D) of JNJ-67856633 and ibrutinib in combination in participants with B cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Cotargeting of BTK and MALT1 overcomes resistance to BTK inhibitors in mantle cell lymphoma.
   Jiang VC, Liu Y, Lian J, Huang S, et al · · 2023 · cited 28× · PMID 36719376 · DOI 10.1172/jci165694
2. Combining precision oncology and immunotherapy by targeting the MALT1 protease.
   Mempel TR, Krappmann D. · · 2022 · cited 19× · PMID 36270731 · DOI 10.1136/jitc-2022-005442
3. MALT1-dependent cleavage of CYLD promotes NF-κB signaling and growth of aggressive B-cell receptor-dependent lymphomas.
   Minderman M, Lantermans HC, Grüneberg LJ, Cillessen SAGM, et al · · 2023 · cited 17× · PMID 36922488 · DOI 10.1038/s41408-023-00809-7
4. Oncogene-induced MALT1 protease activity drives posttranscriptional gene expression in malignant lymphomas.
   Wimberger N, Ober F, Avar G, Grau M, et al · · 2023 · cited 13× · PMID 37623434 · DOI 10.1182/blood.2023021299
5. Pharmacological Inhibition of MALT1 Ameliorates Autoimmune Pathogenesis and Can Be Uncoupled From Effects on Regulatory T-Cells.
   Biswas S, Chalishazar A, Helou Y, DiSpirito J, et al · · 2022 · cited 13× · PMID 35615349 · DOI 10.3389/fimmu.2022.875320
6. A small-molecule inhibitor of BCL10-MALT1 interaction abrogates progression of diffuse large B cell lymphoma.
   Kang H, Maurer LM, Cheng J, Smyers M, et al · · 2025 · cited 4× · PMID 40231473 · DOI 10.1172/jci164573
7. Targeted Agents in the Treatment of Indolent B-Cell Non-Hodgkin Lymphomas.
   Minson A, Tam C, Dickinson M, Seymour JF. · · 2022 · cited 4× · PMID 35267584 · DOI 10.3390/cancers14051276
8. MALT1 inhibitor MI-2 induces ferroptosis by direct targeting of GPX4.
   Mishima E, O'Neill TJ, Hoefig KP, Chen D, et al · · 2025 · cited 3× · PMID 40343971 · DOI 10.1073/pnas.2507997122