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)

Lymphoma, Non-Hodgkin Clinical Trial

Official title:

A Phase 1, First-in-human Study of JNJ-80948543, a T-cell Redirecting Antibody, in Participants With NHL and CLL

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05424822
• Other study ID #: CR109174
• Secondary ID: 2022-000685-1880
• Status: Recruiting
• Phase: Phase 1
• Start date: August 18, 2022
• Est. completion date: November 13, 2026

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: November 13, 2026
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• JNJ-80948543
JNJ-80948543 will be administered as SC injection.

Locations

Country	Name	City	State
Australia	Macquarie University Hospital	Macquarie University
Australia	The Alfred Hospital	Melbourne
Australia	Linear Clinical Research Ltd	Nedlands
Australia	Scientia Clinical Research	Randwick
China	Sun Yat-Sen University Cancer Center	Guangzhou
China	Tianjin cancer hospital	Tianjin
China	Union Hospital Tongji Medical College of Huazhong University of Science and Technology	Wuhan
Denmark	Rigshospitalet	Copenhagen
Denmark	Odense University Hospital	Odense
France	CHRU de Lille Hopital Claude Huriez	Lille Cedex
France	Institut Curie	Paris
France	Institut Universitaire du cancer de Toulouse-Oncopole	Toulouse Cedex 9
Israel	Carmel Medical Center	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Poland	Uniwersyteckie Centrum Kliniczne Osrodek Badan Klinicznych Wczesnych Faz	Gdansk
Poland	Centrum Medyczne Pratia Poznan	Skorzewo
United States	City of Hope	Duarte	California
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Texas Transplant Institute	San Antonio	Texas
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Australia,  China,  Denmark,  France,  Israel,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 2 Years 5 months
Primary	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 2 Years 5 months
Primary	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 2 Years 5 months
Secondary	Serum Concentration of JNJ-80948543	Serum samples will be analyzed to determine concentrations of JNJ-80948543 using a validated, specific, and sensitive method.	Up to 2 Years 5 months
Secondary	Number of Participants with Presence of Anti-Drug Antibodies of JNJ-80948543	Number of participants with presence of anti-drug antibodies of JNJ-80948543 will be assessed.	Up to 2 Years 5 months
Secondary	Overall Response Rate (ORR)	ORR is defined as the percentage of participants who have a best response of partial response (PR) or better.	Up to 2 Years 5 months
Secondary	Complete Response (CR) Rate	CR rate is defined as the percentage of participants who achieve a best response of CR.	Up to 2 Years 5 months
Secondary	Rate of VGPR or Better for Participants with Waldenstrom Macroglobulinemia (WM)	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.	Up to 2 Years 5 months
Secondary	Time to Response (TTR)	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.	Up to 2 Years 5 months
Secondary	Duration of Response (DOR)	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.	Up to 2 Years 5 months