Description:
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.
Title
- Brief Title: A Study of JNJ-75348780 in Participants With Non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)
- Official Title: A Phase 1, First-in-Human, Dose Escalation Study of the JNJ-75348780 Bispecific Antibody Targeting CD3 and CD22 in Participants With NHL and CLL
Clinical Trial IDs
- ORG STUDY ID:
CR108882
- SECONDARY ID:
2020-001183-29
- SECONDARY ID:
75348780LYM1001
- NCT ID:
NCT04540796
Conditions
- Lymphoma, Non-Hodgkin
- Leukemia, Lymphocytic, Chronic, B-Cell
Interventions
Drug | Synonyms | Arms |
---|
JNJ-75348780 | | Part A: Dose Escalation |
Purpose
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.
Detailed Description
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 2.7 years. 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.
Trial Arms
Name | Type | Description | Interventions |
---|
Part A: Dose Escalation | Experimental | Participants will receive once weekly dose or may receive every 2 weeks (Q2W) administration of JNJ-75348780. The dose levels will be escalated sequentially based on the decisions of the Study Evaluation Team (SET), along with the potential exploration of other routes of administration and schedules, until one or more recommended Phase 2 Doses (RP2D) have been identified. | |
Part B: Cohort Expansion | Experimental | Participants will receive JNJ-75348780 at one of the putative RP2Ds determined in Part A. | |
Eligibility Criteria
Inclusion Criteria:
- Histologic documentation of disease: B-cell NHL or CLL requiring therapy; All
participants must have relapsed or refractory disease with no other approved therapies
available that would be more appropriate in the investigator's judgment.
B cell NHL as defined per the 2016 World Health Organization (WHO) classification: In
addition, the following disease-specific criteria outlined below must be met a) If diffuse
large B-cell lymphoma (DLBCL): received, or not eligible for high-dose chemotherapy and
autologous stem cell transplantation with curative intent, b) If follicular lymphoma (FL)/
marginal zone lymphoma (MZL) (except mucosa-associated lymphoid tissue [MALT]), or
Waldenstrom macroglobulinemia (WM): previously treated with a minimum of 2 prior lines of
systemic therapy, with at least 1 prior line containing an anti-CD20 antibody, c) If mantle
cell lymphoma (MCL): previously treated with at least 1 prior line of systemic therapy
containing an anti-CD20 antibody. CLL or small lymphocytic lymphoma (SLL): relapsed or
refractory with at least 2 prior lines of therapy to include a bruton tyrosine kinase
inhibitor (BTKi) and/or a B-cell lymphoma (BCL)2 inhibitor, if eligible. For Part B:
participants must have measurable disease as defined by the appropriate disease response
criteria
- Eastern Cooperative Oncology Group (ECOG) performance status Grade of 0 or 1
- Cardiac parameters within the following range: corrected QT interval (QTc intervals
corrected using Fridericia's formula [QTcF]) less than or equal to (<=) 480
milliseconds (ms) based on the average of triplicate assessments performed no more
than 5 (plus minus [+ -] 3) minutes apart
- Women of childbearing potential must have a negative highly sensitive serum pregnancy
test (Beta human chorionic gonadotropin) at screening and prior to the first dose of
study drug
- Women must be: a) not of childbearing potential, b) of childbearing potential and
practicing a highly effective, preferably user independent method of contraception
(failure rate of less than (<) 1 percent (%) per year when used consistently and
correctly) and agrees to remain on a highly effective method while receiving study
drug and until 90 days after last dose
Exclusion Criteria:
- Known active central nervous system (CNS) involvement with lymphoma
- Prior solid-organ transplantation
- Either of the following: a) received an autologous stem cell transplant <=3 months
before the first dose of JNJ 75348780, b) prior treatment with allogenic stem cell
transplant <= 6 months before the first dose of JNJ-75348780, or has evidence of graft
versus host disease that requires immunosuppressant therapy
- Prior chemotherapy, targeted therapy, immunotherapy or radiotherapy (with the
exclusion of palliative radiation to limited sites that do not interfere with response
assessment based on a sufficient number of other sites), within 2 weeks before the
first administration of study drug. For investigational agents where the half-life is
known, there should be a treatment-free window of at least 2 weeks or 5 half-lives,
whichever is longer. For investigational agents with long half-lives a wash-out of 4
weeks is acceptable
- Active autoimmune disease that requires systemic immunosuppressive medications
(example, chronic corticosteroid, methotrexate, or tacrolimus)
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Part A and Part B: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability |
Time Frame: | Up to 2.7 years |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | Area Under the Concentration-time Curve From Time Zero to End of Dosing Interval (AUCtau) of JNJ-75348780 |
Time Frame: | Up to 2.7 years |
Safety Issue: | |
Description: | AUCtau is the measure of the serum drug concentration from time zero to end of dosing interval. |
Measure: | Maximum Observed Serum Concentration (Cmax) of JNJ-75348780 |
Time Frame: | Predose, 48 hours postdose (up to 2.7 years) |
Safety Issue: | |
Description: | Cmax is the maximum observed serum concentration of JNJ-75348780. |
Measure: | Minimum Observed Serum Concentration (Cmin) of JNJ-75348780 |
Time Frame: | Predose, 48 hours postdose (up to 2.7 years) |
Safety Issue: | |
Description: | Cmin is the minimum observed serum concentration of JNJ-75348780. |
Measure: | Objective Response Rate (ORR) |
Time Frame: | Up to 2.7 years |
Safety Issue: | |
Description: | ORR is defined as the percentage of participants who achieve a complete response (CR) and 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. |
Measure: | Complete Response (CR) Rate |
Time Frame: | Up to 2.7 years |
Safety Issue: | |
Description: | 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. |
Measure: | Time to Response (TTR) |
Time Frame: | Up to 2.7 years |
Safety Issue: | |
Description: | 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. |
Measure: | Duration of Response (DOR) |
Time Frame: | Up to 2.7 years |
Safety Issue: | |
Description: | 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. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Janssen Research & Development, LLC |
Last Updated
August 30, 2021