A Study of JNJ-80948543, a T-cell Redirecting CD79b x CD20 x CD3 Trispecific Antibody, in Participants With Non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)

NCT05424822 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: CR1091742022-000685-1880948543LYM10012023-504187-42-00
• Study Type: interventional
• Target: 167
• Locations: 8 countries
• Sites: 29

Brief Summary

The purpose of this study is to characterize safety and to determine the putative recommended Phase 2 dose(s) (RP2D\[s\]), optimal dosing schedule(s) and route(s) of administration of JNJ-80948543 in Part A (Dose Escalation) and to further characterize the safety of JNJ-80948543 at the putative RP2D(s) in Part B (Cohort Expansion).

Conditions

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

Outcome Measures

Primary Outcomes (3)

• Number of Participants with Dose-limiting Toxicity (DLT)

  Number of participants with DLT will be reported. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.

  Up to 4 Years 3 months

• Number of Participants with Adverse Events (AEs)

  An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention.

  Up to 4 Years 3 months

• Number of Participants with AE by Severity

  Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Severity scale ranges from Grade 1 (Mild) to Grade 4 (Life-threatening). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) will be graded as per American Society for Transplantation and Cellular Therapy (ASTCT).

  Up to 4 Years 3 months

Secondary Outcomes (7)

• Serum Concentration of JNJ-80948543

  Up to 4 Years 3 months

• Number of Participants with Presence of Anti-Drug Antibodies of JNJ-80948543

  Up to 4 Years 3 months

• Overall Response Rate (ORR)

  Up to 4 Years 3 months

• Complete Response (CR) Rate

  Up to 4 Years 3 months

• Rate of VGPR or Better for Participants with Waldenstrom Macroglobulinemia (WM)

  Up to 4 Years 3 months

Study Arms (2)

Part A: Dose Escalation

EXPERIMENTAL

Participants will receive JNJ-80948543 either by subcutaneous (SC) or intravenous (IV) administration to determine the putative recommended Phase 2 dose (RP2D) dosing schedule(s) and route(s) of administration based on safety, pharmacokinetic, pharmacodynamic, and preliminary assessment of efficacy across several dose regimens.

Drug: JNJ-80948543

Part B: Cohort Expansion

EXPERIMENTAL

Participants will receive JNJ-80948543 by SC or IV administration.

Drug: JNJ-80948543

Interventions

JNJ-80948543 DRUG

JNJ-80948543 will be administered as SC or IV injection.

Part A: Dose Escalation; Part B: Cohort Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic documentation of disease: B-cell non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (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:
• If diffuse large B-cell lymphoma (DLBCL) or other high-Grade B-cell lymphoma: Received, or not eligible for high-dose chemotherapy and autologous stem cell transplantation with curative intent or deemed not eligible or fit for an alternative 2nd line therapy. Participants may be eligible if relapsing after chimeric antigen receptors (CAR-T) cell treatment or while waiting for a CAR-T cell treatment.
• If transformed lymphoma from low Grade B-cell malignancies: Received or not a candidate for an approved first-line regimen for DLBCL and received or not eligible for high-dose chemotherapy and autologous stem cell transplantation with curative intent.
• If follicular lymphoma (FL) (all grades): Previously treated with a minimum of 2 prior lines of systemic therapy, with at least one prior line containing an anti-CD20 antibody.
• If mantle cell lymphoma (MCL), marginal zone lymphoma (MZL) (including nodal, extranodal/MALT, and splenic MZL subtypes): Previously treated with at least 2 lines of systemic therapy. H.pylori-positive gastric MALT lymphoma must have failed prior H. pylori eradication therapy as one of their prior lines .
• Waldenstrom macroglobulinemia (WM): Previously treated with at least 1 line of systemic therapy.
• small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL/SLL): Relapsed or refractory with at least 2 prior lines of therapy, including a Bruton tyrosine kinase inhibitor (BTK) inhibitor or a BCL2 inhibitor, if eligible. In addition 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 based on the average of triplicate assessments performed no more than 5 (plus minus \[+-\] 3) minutes apart
• A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test (beta- human chorionic gonadotropin) at screening and must agree to further serum or urine pregnancy tests prior to the first dose, during the study and until 3 months after the last dose of study treatment
• A female participant must agree not to be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 3 months after the last dose of study treatment

You may not qualify if:

• Known active central nervous system (CNS) involvement; Lymphoma with CNS involvement may be allowed in pharmacokinetic/ pharmacodynamic (PK/PD) and expansion cohorts if approved by the study evaluation team (SET)
• Prior solid-organ transplantation
• Autoimmune or inflammatory disease requiring systemic steroids or other immunosuppressive agents (example, methotrexate or tacrolimus) within 1 year prior to first dose of study drug
• Toxicity from prior anticancer therapy has not resolved to baseline levels or to Grade \<= 1 (except alopecia, vitiligo, peripheral neuropathy, or endocrinopathies that are stable on hormone replacement, which may be Grade 2)
• Clinically significant pulmonary compromise, particularly the need for supplemental oxygen use to maintain adequate oxygenation

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (29)

City of Hope

Duarte, California, 91010, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Macquarie University Hospital

Macquarie University, 2109, Australia

Location

The Alfred Hospital

Melbourne, 3004, Australia

Location

Linear Clinical Research Ltd

Nedlands, 6009, Australia

Location

Scientia Clinical Research

Randwick, 2031, Australia

Location

Chongqing University Cancer Hospital

Chongqing, 400044, China

Location

Sun Yat Sen University Cancer Center

Guangzhou, 510060, China

Location

Tianjin cancer hospital

Tianjin, 300060, China

Location

Union Hospital Tongji Medical College of Huazhong University of Science and Technology

Wuhan, 430030, China

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Odense University Hospital

Odense, 5000, Denmark

Location

CHRU de Lille Hopital Claude Huriez

Lille, 59037, France

Location

Institut Curie

Paris, 75005, France

Location

Institut de Cancerologie Strasbourg Europe ICANS

Strasbourg, 67033, France

Location

Institut Universitaire du cancer de Toulouse-Oncopole

Toulouse, 31059, France

Location

Carmel Medical Center

Haifa, 34362, Israel

Location

Hadassah Medical Center

Jerusalem, 9112001, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

National Cancer Center Hospital East

Kashiwa, 277 8577, Japan

Location

Aichi Cancer Center

Nagoya, 464 8681, Japan

Location

The Cancer Institute Hospital of JFCR

Tokyo, 135 8550, Japan

Location

Uniwersyteckie Centrum Kliniczne Osrodek Badan Klinicznych Wczesnych Faz

Gdansk, 80 214, Poland

Location

Aidport Sp z o o

Skorzewo, 60-185, Poland

Location

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2022
• First Posted: June 21, 2022
• Study Start: August 18, 2022
• Primary Completion: October 31, 2025
• Study Completion (Estimated): July 30, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

JP (3); CN (4); US (7); FR (4); AU (4); IL (3); DK (2); PL (2)