The purpose of this study is to determine the recommended Phase 2 dose regimen or the maximum tolerated dose of JNJ-67856633 in participants with relapsed/ refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia.
Non-Hodgkin lymphoma (NHL) represents a diverse set of diseases. Among them diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of NHL, accounting for 30 percent (%) to 40% of all newly diagnosed cases. Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a key mediator of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) signaling pathway and has been shown to play a critical role in different types of lymphoma, including activated B cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL). JNJ-67856633 is a MALT1 inhibitor and will be administered orally. The study will evaluate the following: Dose Escalation (Part 1): One or more recommended Phase 2 dose (RP2Ds) of JNJ-67856633. Cohort Expansion (Part 2): JNJ-67856633 is well tolerated and achieves antitumor responses at the RP2D. The study consists of screening phase (less than or equal to 28 days before first dose), treatment phase (from Cycle 1 Day 1 till end of treatment visit \[within 30 (+7) days after the last dose\]) and post-treatment phase. A prescreening period may also apply to participants in select cohorts in Part 2. The total study duration will be approximately 4 years and 11 months. Efficacy assessments will include radiographic image assessments, positron emission tomography scan, bone marrow assessment, endoscopy or colonoscopy etc. Safety will be monitored throughout the study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
226
JNJ-67856633 capsule will be administered orally.
Part 1: Dose-Limiting Toxicity (DLT)
The DLTs are based on drug related adverse events and defined as any of the following events: any toxicity that would require discontinuation of treatment; and/or hematological / non-hematological toxicity of Grade 3 or higher.
Time frame: Approximately 21 days
Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Time frame: Up to 4 years and 11 months
JNJ-67856633 Plasma Concentrations
Concentration assessment will be done to evaluate the effect of JNJ-67856633.
Time frame: Up to 4 years and 11 months
Part 1 and Part 2: Overall Response Rate (ORR)
ORR is defined as the percentage of participants who have a partial response (PR) and complete response (CR) according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL), non-Hodgkin lymphoma and Waldenstrom macroglobulinemia response criteria.
Time frame: Up to 4 years and 11 months
Part 1 and Part 2: Complete Response Rate
Complete response rate is defined as the percentage of participants who achieve a best response of CR according to the iwCLL, non-Hodgkin lymphoma and Waldenstrom macroglobulinemia response criteria.
Time frame: Up to 4 years and 11 months
Part 1 and Part 2: Time to Response (TTR)
TTR is defined for participants who achieved PR or CR as the time from the first dose of study drug to first response of PR or CR.
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City of Hope
Duarte, California, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Weill Cornell Medicine
New York, New York, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
MD Anderson
Houston, Texas, United States
Monash Medical Centre
Clayton, Australia
Peter MacCallum Cancer Centre
Melbourne, Australia
Linear Clinical Research Ltd
Nedlands, Australia
Scientia Clinical Research
Randwick, Australia
...and 37 more locations
Time frame: Up to 4 years and 11 months
Part 1 and Part 2: Duration of Response (DoR)
DoR is defined for participants who achieved PR or CR as the time between the date of initial documentation of PR or CR to the date of first documented evidence of disease progression or death, whichever comes first.
Time frame: Up to 4 years and 11 months