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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell

Treatments: Drug: Ibrutinib; Drug: JNJ-67856633

Study type: Interventional

Funder types: Industry

Identifiers

NCT04876092

CR109010

2021-000191-12 (EudraCT Number)

67856633LYM1002 (Other Identifier)

Details and patient eligibility

About

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).

Full description

Non-Hodgkin lymphoma (NHL) represents the most frequent hematologic malignancy in the world and represents a diverse set of diseases. JNJ-67856633-ZAF (referred as JNJ-67856633) is an orally bioavailable, potent, and selective first-in-class mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1) inhibitor. JNJ-67856633 binds to an allosteric site on MALT1 with a mixed-type mechanism. Ibrutinib is a first-in-class, orally administered, potent, orally administered covalently binding small-molecule inhibitor of Bruton's tyrosine kinase (BTK), as well as interleukin-2-inducible kinase (ITK), a tyrosine protein (Tec) kinase family member present in T cells. The doses will be escalated in the study and one or more recommended Phase 2 dose (RP2Ds) of JNJ-67856633 will be determined. The study is divided into 3 periods: a screening phase, a treatment phase, and a post-treatment follow-up phase. Efficacy assessments will include radiographic image assessments, positron emission tomography scan, bone marrow assessment, endoscopy etc. Safety assessment like physical examination, vital signs, electrocardiogram (ECG), eastern cooperative oncology group (ECOG) performance status, and adverse events monitoring will be performed during the study. Total duration of the study will be up to 2 years and 9 months.

Enrollment: 45 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
• Cardiac parameters within the specified range
• Women of childbearing potential must agree to all of the following during the study and for 3 months after the last dose of study drug: a) use a barrier method of contraception; b) use a highly effective contraceptive methods; c) not to donate eggs (ova, oocytes) or freeze them for future use for the purposes of assisted reproduction during the study; d) not to plan to become pregnant; e) not to breast-feed
• Willing and able to adhere to the lifestyle restrictions specified in this protocol
• Participants must have tumor tissue availability
• Adequate organ functions

Exclusion criteria

• Known (active) Central Nervous System (CNS) involvement
• Prior treatment with JNJ-67856633 or another MALT1 inhibitor that is associated with disease progression or intolerable toxicities

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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45 participants in 1 patient group

JNJ-67856633 and Ibrutinib

Experimental group

Description:

Participants will receive JNJ-67856633 together with Ibrutinib orally on a 21-day cycle. The dose levels will be escalated based on the dose limiting toxicities (DLT) evaluation by Study Evaluation Team (SET).

Treatment:

Drug: JNJ-67856633

Drug: Ibrutinib