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

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.

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