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)

• ClinicalTrials.gov Identifier: NCT05424822
• Recruitment Status: Recruiting
• First Posted: June 21, 2022
• Last Update Posted: April 24, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: June 15, 2022
• First Posted Date: June 21, 2022
• Last Update Posted Date: April 24, 2024
• Actual Study Start Date: August 18, 2022
• Estimated Primary Completion Date: July 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 15, 2022)

• Number of Participants with Dose-limiting Toxicity (DLT) [ Time Frame: Up to 2 Years 5 months ]
  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.
• Number of Participants with Adverse Events (AEs) [ Time Frame: Up to 2 Years 5 months ]
  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.
• Number of Participants with AE by Severity [ Time Frame: Up to 2 Years 5 months ]
  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).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 15, 2022)

• Serum Concentration of JNJ-80948543 [ Time Frame: Up to 2 Years 5 months ]
  Serum samples will be analyzed to determine concentrations of JNJ-80948543 using a validated, specific, and sensitive method.
• Number of Participants with Presence of Anti-Drug Antibodies of JNJ-80948543 [ Time Frame: Up to 2 Years 5 months ]
  Number of participants with presence of anti-drug antibodies of JNJ-80948543 will be assessed.
• Overall Response Rate (ORR) [ Time Frame: Up to 2 Years 5 months ]
  ORR is defined as the percentage of participants who have a best response of partial response (PR) or better.
• Complete Response (CR) Rate [ Time Frame: Up to 2 Years 5 months ]
  CR rate is defined as the percentage of participants who achieve a best response of CR.
• Rate of VGPR or Better for Participants with Waldenstrom Macroglobulinemia (WM) [ Time Frame: Up to 2 Years 5 months ]
  The response criteria planned to be used for participants with WM includes a category of VGPR, which is clinically understood to be better than PR but not as good as CR. For participants with WM, this rate is defined as the proportion of participants who achieve a best response of VGPR or better.
• Time to Response (TTR) [ Time Frame: Up to 2 Years 5 months ]
  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.
• Duration of Response (DOR) [ Time Frame: Up to 2 Years 5 months ]
  DOR is defined for participants who achieved a response of PR or better as the time between the date of initial documentation of first response of PR or better to the date of first documented evidence of progressive disease or death.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Official Title: A Phase 1, First-in-human Study of JNJ-80948543, a T-cell Redirecting Antibody, in Participants With NHL and CLL
• 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-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).
• Detailed Description: B-cell non-Hodgkin lymphoid malignancies (NHLs) are defined by clonal populations of B- lymphocytes. JNJ-80948543 is a T-cell redirecting tri-specific antibody that recognizes the cluster of differentiation 3 (CD3) antigen on T lymphocytes and CD79b, and CD20 surface antigens on mature healthy and malignant B- lymphocytes. The study will be conducted in 2 parts: Part A (dose Escalation) and part B (Cohort Expansion). Each of the 2 parts of this study is divided into 3 periods, a screening phase, a treatment phase and a post-treatment follow-up phase. The total duration of the study will be up to 2 year 5 months. Efficacy assessments will include radiographic image assessments, positron emission tomography scan, bone marrow assessment, endoscopy, physical examinations. Safety will be monitored throughout the study.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

Drug: JNJ-80948543

JNJ-80948543 will be administered as SC injection.

Study Arms

• Experimental: Part A: Dose Escalation
  Participants will receive JNJ-80948543 by subcutaneous (SC) administration to determine the putative recommended Phase 2 dose (RP2D) and dosing schedule(s) based on safety, pharmacokinetic, pharmacodynamic, and preliminary assessment of efficacy across several dose regimens.
  Intervention: Drug: JNJ-80948543
• Experimental: Part B: Cohort Expansion
  Participants will receive JNJ-80948543 by SC administration.
  Intervention: Drug: JNJ-80948543

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 15, 2022): 180
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 30, 2026
• Estimated Primary Completion Date: July 31, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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 intervention

Exclusion Criteria:

• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Contact; 844-434-4210; Participate-In-This-Study@its.jnj.com

• Listed Location Countries: Australia, China, Denmark, France, Israel, Poland, United States

Administrative Information

• NCT Number: NCT05424822
• Other Study ID Numbers: CR109174; 2022-000685-18 ( EudraCT Number ); 80948543LYM1001 ( Other Identifier: Janssen Research & Development, LLC ); 2023-504187-42-00 ( Registry Identifier: EUCT number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
• URL: https://www.janssen.com/clinical-trials/transparency

• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: April 2024