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

NCT ID: NCT04540796

Last Updated: 2025-10-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 147 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-20
• Study Completion Date: 2025-09-09

Brief Summary

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 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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A: Dose Escalation

Participants will receive 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.

Group Type: EXPERIMENTAL

JNJ-75348780

Intervention Type: DRUG

Participants will receive JNJ-75348780 by subcutaneous (SC) administration.

Part B: Cohort Expansion

Participants will receive JNJ-75348780 at one of the putative RP2Ds determined in Part A.

Group Type: EXPERIMENTAL

JNJ-75348780

Intervention Type: DRUG

Participants will receive JNJ-75348780 by subcutaneous (SC) administration.

Interventions

JNJ-75348780

Participants will receive JNJ-75348780 by subcutaneous (SC) administration.

Intervention Type: DRUG

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 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. Participants who received prior treatment with anti-CD20 * anti-CD3 bispecific therapy will be excluded until a dedicated cohort(s) is opened as determined by the SET
• Active autoimmune disease that requires systemic immunosuppressive medications (example, chronic corticosteroid, methotrexate, or tacrolimus)
• History of malignancy (other than the disease under study in the cohort to which the participant is assigned) within 1 year prior to the first administration of study drug. Exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy which in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 1 year before the first dose of study drug. Concomitant malignancies that are unlikely to progress and/or preclude evaluation of study endpoints may be allowed after discussion with the Study Responsible Physician

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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

Hadassah Medical Center

Jerusalem, , Israel

Sheba Medical Center

Ramat Gan, , Israel

Tel Aviv Sourasky MC

Tel Aviv, , Israel

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

The Catholic University of Korea Seoul St Marys Hospital

Seoul, , South Korea

Hospital de Vall D'Hebron

Barcelona, , Spain

Hosp. Univ. Germans Trias I Pujol

Barcelona, , Spain

Hosp Univ Fund Jimenez Diaz

Madrid, , Spain

Clinica Univ. de Navarra

Pamplona, , Spain

Hosp Clinico Univ de Salamanca

Salamanca, , Spain

Chang-Gung Memorial Hospital, Kaohsiung

Kaohsiung City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Leicester Royal Infirmary

Leicester, , United Kingdom

Kings College Hospital

London, , United Kingdom

The Christie Nhs Foundation Trust

Manchester, , United Kingdom

Plymouth Hospital NHS Trust

Plymouth, , United Kingdom

Countries

United States; Australia; France; Israel; South Korea; Spain; Taiwan; United Kingdom

Other Identifiers

75348780LYM1001

Identifier Type: OTHER

Identifier Source: secondary_id

2020-001183-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR108882

Identifier Type: -

Identifier Source: org_study_id