The purpose of this study is to characterize safety and to determine the putative recommended Phase 2 dose(s) (RP2D\[s\]) and optimal dosing schedule(s) of JNJ-75348780 in participants with relapsed/ refractory B-cell Non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL) in Part A and to further characterize the safety at the RP2D(s) in Part B.
B-cell lymphoid malignancies include CLL and NHL and are defined by clonal populations of B-lymphocytes expressing identical surface antigens. CD22 is a surface protein specifically expressed on B-lymphocytes and is expressed in B-lymphocytic malignancies. It is known to negatively regulate the B-cell receptor via its cytosolic immunoreceptor tyrosine-based inhibitory motifs. JNJ-75348780 is a novel human bispecific antibody that recognizes the CD3 antigen on T-lymphocytes and the CD22 antigen on mature and malignant B-lymphocytes. JNJ-75348780 is hypothesized to lead to cytotoxicity, T-cell activation, and induction of cytokines upon engagement of CD3 on T-cells and CD22 on malignant B-lymphocytes. The study consists of screening phase, treatment phase and post-treatment phase. The total study duration will be up to 2 years 10 months. Efficacy assessments will include radiographic image assessments, positron emission tomography scan, bone marrow assessment, endoscopy or colonoscopy, physical examinations. Safety will be monitored throughout the study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
147
Participants will receive JNJ-75348780 by subcutaneous (SC) administration.
Part A and Part B: 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 2 years 10 months
Part A and Part B: Number of Participants with AEs by Severity
Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event.
Time frame: Up to 2 years 10 months
Part A and Part B: Number of Participants with Dose-Limiting Toxicity (DLT)
Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Time frame: Up to 28 days
Area Under the Concentration-time Curve From Time Zero to End of Dosing Interval (AUCtau) of JNJ-75348780
AUCtau is the measure of the serum drug concentration from time zero to end of dosing interval.
Time frame: Up to 2 years 10 months
Maximum Observed Serum Concentration (Cmax) of JNJ-75348780
Cmax is the maximum observed serum concentration of JNJ-75348780.
Time frame: Predose, 48 hours postdose (up to 2 years 10 months)
Minimum Observed Serum Concentration (Cmin) of JNJ-75348780
Cmin is the minimum observed serum concentration of JNJ-75348780.
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University of Alabama at Birmingham
Birmingham, Alabama, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Austin Hospital
Heidelberg, Australia
Linear Clinical Research Ltd
Nedlands, Australia
CHRU de Lille Hopital Claude Huriez
Lille, France
CHU Nantes
Nantes, France
Centre hospitalier Lyon-Sud
Pierre-Bénite, France
Rambam Medical Center
Haifa, Israel
Carmel Medical Center
Haifa, Israel
...and 22 more locations
Time frame: Predose, 48 hours postdose (up to 2 years 10 months)
Objective Response Rate (ORR)
ORR is defined as the percentage of participants who achieve a partial response (PR) or better according to the revised response criteria for malignant lymphoma, the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) response criteria and International Workshop for Waldenstrom Macroglobulinemia (IWWM) response criteria.
Time frame: Up to 2 years 10 months
Complete Response (CR) Rate
CR rate is defined as the percentage of participants who achieve a best response of CR according to the revised response criteria for malignant lymphoma, iwCLL response criteria and IWWM response criteria.
Time frame: Up to 2 years 10 months
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 according to the revised response criteria for malignant lymphoma, iwCLL response criteria and IWWM response criteria.
Time frame: Up to 2 years 10 months
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 either the first documented evidence of disease progression or death according to the revised response criteria for malignant lymphoma, iwCLL response criteria and IWWM response criteria.
Time frame: Up to 2 years 10 months