A Study of JNJ-80948543 in Combination With Other CD3 T-Cell Engagers in Participants With Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma (R/R B-Cell NHL)

A Phase 1b Study of JNJ-80948543 in Combination With Other CD3 T-Cell Engagers (TCEs) in Participants With Relapsed/Refractory B-Cell Non-Hodgkin Lymphoid (R/R B-Cell NHL) Malignancies

The purpose of this study is to determine the recommended phase 2 regimen (RP2R) for JNJ-80948543 in combination with JNJ-75348780 (Part 1: Dose Escalation) and to further assess the safety of JNJ-80948543 at the RP2R in combination with JNJ-75348780 (Part 2: Dose Expansion).

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoma, Non-Hodgkin
• Intervention / Treatment: Drug: JNJ-80948543; Drug: JNJ-75348780

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Concord, Australia, 2139
    • Concord Hospital
  • Fitzroy, Australia, 3065
    • St Vincents Hospital Melbourne
  • North Ryde, Australia, 2109
    • Macquarie University Hospital
• Spain
  • Barcelona, Spain, 08036
    • Hosp. Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Hosp Univ Vall D Hebron
  • L'Hospitalet de Llobregat, Spain, 08908
    • Inst. Cat. Doncologia-H Duran I Reynals
  • Madrid, Spain, 28041
    • Hosp. Univ. 12 de Octubre
  • Madrid, Spain, 28007
    • Hosp. Gral. Univ. Gregorio Maranon
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • University Hospitals of Leicester NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologic documentation of diffuse large B-cell lymphoma (DLBCL), including high-grade B-cell lymphoma and DLBCL arising from indolent lymphoma. All participants must have received at least 2 prior lines of therapy
• Participants must have measurable disease as defined by the appropriate disease response criteria
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Hematologic laboratory parameters must meet the required criterias and the values must be without a transfusion or growth factors for at least 7 days prior to the first dose of study drug
• Participants of childbearing potential must have a negative highly sensitive serum pregnancy test (beta (β)-human chorionic gonadotropin) at screening and within 24 hours before the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study

Exclusion Criteria:

• Known active central nervous system involvement (CNS) or leptomeningeal involvement
• 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 defined as the need for supplemental oxygen to maintain adequate oxygenation
• Evidence of clinically significant and/or symptomatic infection (viral, bacterial, or fungal) at the time of study drug initiation. Anti-microbial treatment for infection must be discontinued at least 7 days before the first dose of study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: JNJ-80948543; Participants will receive JNJ-80948543 in combination with JNJ-75348780 to determine the recommended phase 2 regimen (RP2R) in Part 1 (Dose escalation). JNJ-80948543 will be dosed in an escalation manner in combination with fixed doses of JNJ-75348780. In Part 2 (Dose expansion) participants will receive RP2R of JNJ-80948543 as determined in Part 1 in combination with JNJ-75348780.

Drug: JNJ-80948543; JNJ-80948543 will be administered as subcutaneous (SC) or intravenous (IV) injection.; Drug: JNJ-75348780; JNJ-75348780 will be administered as SC injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Dose-limiting Toxicity (DLT)	Number of participants with DLT will be reported. DLTs are defined as any of the treatment-related toxicities: any toxicity that would require discontinuation of treatment; Fatal toxicity; Non-hematologic toxicity (Grade 3 toxicity or higher with exceptions); and Hematologic Toxicity (Grade 4 neutrophil count decrease; Grade 4 febrile neutropenia; Grade 3 febrile neutropenia that does not recover with best supportive care within 7 days; Grade 4 platelet count decrease for >=7 days or Grade >3 with Grade >=2 bleeding; Grade 4 anemia).	Up to 1 year and 10 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 1 year and 10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Concentration of JNJ-80948543 and JNJ-75348780	Serum Concentration for JNJ-80948543 and JNJ-75348780 will be reported.	Up to 1 year and 10 months
Area Under the Curve (AUCtau) for JNJ-80948543 and JNJ-75348780	AUC tau is defined as area under the serum concentration-time curve during a dosing interval for JNJ-80948543 and JNJ-75348780.	Up to 1 year and 10 months
Maximum Serum Concentration (Cmax) for JNJ-80948543 and JNJ-75348780	Cmax for JNJ-80948543 and JNJ-75348780 will be reported.	Up to 1 year and 10 months
Time to Reach Cmax (Tmax) for JNJ-80948543 and JNJ-75348780	Tmax is the time to reach maximum observed serum concentration for JNJ-80948543 and JNJ-75348780.	Up to 1 year and 10 months
Number of Participants with Presence of Anti-Drug Antibodies of JNJ-80948543 and JNJ-75348780	Number of participants with presence of anti-drug antibodies of JNJ-80948543 and JNJ-75348780 will be assessed.	Up to 1 year and 10 months
Overall Response Rate (ORR)	ORR is defined as the percentage of participants who have a best response of partial response (PR) or better as assessed by the investigator based on standard response criteria.	Up to 1 year and 10 months
Complete Response Rate (CRR)	CR is defined as the percentage of participants who achieve a best response of CR as assessed by the investigator based on standard response criteria.	Up to 1 year and 10 months
Duration of Response (DoR)	DOR is defined as the time from the first efficacy evaluation at which the participant meet all criteria for a response of PR or better to the date of first documented evidence of progressive disease or death as assessed by the investigator based on standard response criteria.	Up to 1 year and 10 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2024
• Primary Completion (Estimated): September 7, 2026
• Study Completion (Estimated): September 21, 2026

Study Registration Dates

• First Submitted: October 25, 2024
• First Submitted That Met QC Criteria: October 25, 2024
• First Posted (Actual): October 28, 2024

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: 80948543LYM1002 (Other Identifier: Janssen Research & Development, LLC); 2024-514176-41-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson and 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes