Clinical Trials /

A Study of JNJ-75348780 in Participants With Non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)

NCT04540796

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.

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

DrugSynonymsArms
JNJ-75348780Part 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

NameTypeDescriptionInterventions
Part A: Dose EscalationExperimentalParticipants will receive weekly administration of JNJ-75348780. The dose levels will be escalated sequentially based on the decisions of the Study Evaluation Team (SET), along to the potential exploration of other routes of administration and schedules, until one or more recommended Phase 2 Doses (RP2D) have been identified.
  • JNJ-75348780
Part B: Cohort ExpansionExperimentalParticipants will receive JNJ-75348780 at one of the putative RP2Ds determined in Part A.
  • JNJ-75348780

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: 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 at least 1
        prior line of systemic therapy 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 1 prior line of systemic therapy containing a bruton tyrosine kinase inhibitor (BTKi)
        and 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

May 21, 2021