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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)

Phase 1
Recruiting
Conditions
Lymphoma, Non-Hodgkin
Interventions
Registration Number
NCT06660563
Lead Sponsor
Janssen Research & Development, LLC
Brief Summary

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).

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
40
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 & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
JNJ-80948543JNJ-80948543Participants 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.
JNJ-80948543JNJ-75348780Participants 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.
Primary Outcome Measures
NameTimeMethod
Number of Participants with Dose-limiting Toxicity (DLT)Up to 1 year and 10 months

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).

Number of Participants with Adverse Events (AEs)Up to 1 year and 10 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.

Secondary Outcome Measures
NameTimeMethod
Serum Concentration of JNJ-80948543 and JNJ-75348780Up to 1 year and 10 months

Serum Concentration for JNJ-80948543 and JNJ-75348780 will be reported.

Area Under the Curve (AUCtau) for JNJ-80948543 and JNJ-75348780Up to 1 year and 10 months

AUC tau is defined as area under the serum concentration-time curve during a dosing interval for JNJ-80948543 and JNJ-75348780.

Maximum Serum Concentration (Cmax) for JNJ-80948543 and JNJ-75348780Up to 1 year and 10 months

Cmax for JNJ-80948543 and JNJ-75348780 will be reported.

Time to Reach Cmax (Tmax) for JNJ-80948543 and JNJ-75348780Up to 1 year and 10 months

Tmax is the time to reach maximum observed serum concentration for JNJ-80948543 and JNJ-75348780.

Number of Participants with Presence of Anti-Drug Antibodies of JNJ-80948543 and JNJ-75348780Up to 1 year and 10 months

Number of participants with presence of anti-drug antibodies of JNJ-80948543 and JNJ-75348780 will be assessed.

Overall Response Rate (ORR)Up to 1 year and 10 months

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.

Complete Response Rate (CRR)Up to 1 year and 10 months

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.

Duration of Response (DoR)Up to 1 year and 10 months

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.

Trial Locations

Locations (11)

Inst. Cat. Doncologia-H Duran I Reynals

🇪🇸

L Hospitalet De Llobregat, Spain

Concord Hospital

🇦🇺

Concord, Australia

St Vincents Hospital Melbourne

🇦🇺

Fitzroy, Australia

Macquarie University Hospital

🇦🇺

North Ryde, Australia

Hosp Univ Vall D Hebron

🇪🇸

Barcelona, Spain

Hosp. Clinic de Barcelona

🇪🇸

Barcelona, Spain

Hosp. Gral. Univ. Gregorio Maranon

🇪🇸

Madrid, Spain

Hosp. Univ. 12 de Octubre

🇪🇸

Madrid, Spain

China Medical University Hospital

🇨🇳

Taichung, Taiwan

National Taiwan University Hospital

🇨🇳

Taipei City, Taiwan

University Hospitals Of Leicester Nhs Trust

🇬🇧

Leicester, United Kingdom

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