A Study of JNJ-90014496 in Participants With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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This is a Phase Ib multicenter, open-label study of JNJ-90014496, an autologous bi-specific chimeric antigen receptor (CAR) T-cell therapy, targeting both cluster of differentiation (CD) CD19 and CD20 for the treatment of adult participants with relapsed or refractory B-Cell non-Hodgkin lymphoma (r/r B-NHL).

Official Title
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A Phase Ib Multicenter, Open-Label, Study of JNJ-90014496, an Autologous CD19/CD20 Bi-specific CAR-T Cell Therapy in Adult Participants With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Conditions
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Relapsed or Refractory B Cell Non-Hodgkin Lymphoma

Intervention / Treatment
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* Biological: JNJ-90014496


Participation Criteria
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Eligibility Criteria
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Participant must be greater than or equal to (>=) 18 years of age, at the time of signing informed consent Diagnosis of mature aggressive large B cell non-Hodgkin lymphoma or follicular lymphoma Tumor must be histologically confirmed cluster of differentiation (CD)19 and/or CD20 positive Must have relapsed or refractory disease with the following indications for each histologic subtype: Mature aggressive large B cell non-Hodgkin lymphoma (NHL) and follicular lymphoma Grade 3b: Participants must have >= 2 lines of systemic therapy, or >= 1 line of systemic therapy for participants who are ineligible for autologous stem cell transplant; Follicular lymphoma Grade 1-3a and marginal zone lymphoma: Participants must have >= 2 prior lines of anti-neoplastic systemic therapy. Participants also must have prior exposure to an anti-CD20 monoclonal antibody Measurable disease as defined by Lugano 2014 classification Eastern cooperative oncology group (ECOG) performance status of either 0 or 1 Exclusion Criteria Diagnosis of Human herpes virus (HHV) 8-positive diffuse large B Cell lymphoma (DLBCL) Prior allogeneic hematopoietic stem cell transplantation (HSCT) Autologous stem cell transplant within 12 weeks of chimeric antigen receptor (CAR) T cell infusion Uncontrolled active infections History of deep vein thrombosis or pulmonary embolism within six months of infusion (except for line associated deep vein thrombosis [DVT]) History of stroke, unstable angina, myocardial infarction, congestive heart failure New York Heart Association (NYHA) Class III or IV, severe cardiomyopathy or ventricular arrhythmia requiring medication or mechanical control within 6 months of screening History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease or neurodegenerative disorder Known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system Current active liver or biliary disease (except for Gilbert's syndrome or asymptomatic gallstones)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JNJ-90014496<br>Participants will receive intravenous (IV) infusion of autologous JNJ-90014496 on Day 1. | Biological: JNJ-90014496<br>* JNJ-90014496, an autologous bi-specific chimeric antigen receptor (CAR) - T cell therapy targeting Cluster of differentiation (CD)19 and CD20.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Adverse Events (AEs) [Safety and Tolerability] | Occurrence of any AEs, including dose limiting toxicities (DLTs). | Up to 24 months | 
| Determination of the Recommended Phase 2 Dose (RP2D) of JNJ-90014496 in Participants with Relapsed or Refractory B-cell non-Hodgkin lymphoma (B-NHL) | Based on the assessment of DLTs rates and overall safety profile. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response (OR) | Complete response (CR) and partial response (PR) will be assessed by Lugano 2014 guidelines. | Up to 24 months | 
| Time to Response (TTR) | The time from the date of JNJ-90014496 infusion to the first documented CR or PR will be assessed by Lugano 2014 guidelines. | Up to 24 months | 
| Duration of Response (DOR) | The time from the first documented CR or PR to relapse or death, whichever occurs first will be assessed by Lugano 2014 guidelines. | Up to 24 months | 
| Pharmacokinetic Evaluation of JNJ-90014496 | JNJ-90014496 blood levels will be reported. | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD19/CD20-directed CAR-T Cells