A phase 1b/2 multicenter, open-label, study of JNJ-90014496, an autologous CD19/CD20 Bi-specific CAR-T cell therapy in adult participants with B-cell Non-Hodgkin lymphoma
Non-Hodgkin lymphoid malignancies
This is an open-label, single-drug administration study. Up to 12 adult participants with r/r aggressive B-cell NHL may be enrolled into a Run-In dose level. After completion of the Run-In, an aggressive lymphoma and an indolent lymphoma Dose Expansion cohort may open. Up to approx. 40 participants may be enrolled in each Dose Expansion cohort, allowing for up to approx. 92 participants to be enrolled in total. For both the Run-In and Dose Expansion, the study periods and durations for participants are: • Screening: <28 days before apheresis • Apheresis/Enrollment • Bridging therapy: For participants at high risk of experiencing disease progression during the manufacture of the JNJ-90014496 drug product and before lymphodepletion, a bridging therapy is allowed at the investigator’s discretion and the Sponsor’s approval. • Lymphodepletion: Day -5 to Day -3 (window to begin lymphodepletion: Day -7 to Day -5) • JNJ-90014496 single infusion: Day 1 • Post-infusion follow-up: Beginning after JNJ-90014496 infusion (DLT period: Days 1 to 29) and continuing up to Day 90 • Post-treatment follow-up: Beginning after post-infusion follow-up and continuing 2 years post-infusion • Long-term follow-up: beginning after post-treatment follow-up
Current key inclusion criteria as of 31/03/2026: 1. Participant must be greater than or equal to (>=) 18 years of age, at the time of signing informed consent 2. Tumor must be histologically confirmed cluster of differentiation (CD)19 and/or CD20 positive 3. Must meet the indications for each subtype in Phase 1b as specified in protocol and Phase 2 participants must have following: - Diagnosis of Large B-cell lymphoma (LBCL), Follicular large B-cell lymphoma (FLBCL), or transformation of indolent lymphoma; - Received at least 2 prior lines of systemic therapy; - Relapsed or refractory disease defined as 1 or more of the following: Stable disease or Progressive disease (PD) as best response to most recent anti-lymphoma therapy OR disease progression or recurrence after a partial response (PR) or complete response (CR) to most recent anti lymphoma therapy; - cohort specific requirements as mentioned in protocol. 4. Measurable disease as defined by Lugano 2014 classification 5. Eastern Cooperative Oncology Group (ECOG) performance status of either 0 to 2 _____ Previous key inclusion criteria: 1. Participant must be greater than or equal to (>=) 18 years of age, at the time of signing informed consent 2. All participants must have relapsed or refractory disease for each histologic subtype - Mature aggressive large B cell NHL and Follicular Lymphoma Grade 3b: Participants must have >= 2 lines of systemic therapy or >=1 line of systemic therapy in case of participants ineligible for high-dose chemotherapy and autologous Hematopoietic stem cell transplantation (HSCT). Participants also must have had exposure to an anthracycline and an anti-CD20 targeted agent-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 3. Tumor must be cluster of differentiation (CD) 20 positive 4. Measurable disease as defined by Lug
Current key exclusion criteria as of 31/03/2026: 1. History of symptomatic deep vein thrombosis or pulmonary embolism within six months of apheresis (line associated deep vein thrombosis is allowed) 2. 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 six months of apheresis 3. History of a seizure disorder, dementia, cerebellar disease or neurodegenerative disorder 4. Known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system 5. Current active liver or biliary disease (except for Gilbert's syndrome or asymptomatic gallstones) 6. Evidence of active viral or bacterial infection requiring systemic antimicrobial therapy, or uncontrolled systemic fungal infection 7. Diagnosis of Human herpesvirus 8 positive DLBCL or T cell or histiocyte rich large B cell lymphoma or Burkitt and high grade B cell lymphoma with 11q aberrations (previously Burkitt like lymphoma) or Richter's transformation or lymphomatoid granulomatosis or plasmablastic lymphoma or Waldenstrom's macroglobulinaemia 8. Any prior solid organ or allogeneic stem cell transplantation 9. Autologous stem cell transplant within 12 weeks of apheresis; prior CAR T cell therapy within 12 weeks of apheresis _____ Previous key exclusion criteria: 1. Diagnosis of Human herpes virus (HHV) 8-positive Diffuse large B Cell lymphoma (DLBCL) 2. Prior allogeneic Hematopoietic stem cell transplantation (HSCT) 3. Autologous stem cell transplant within 12 weeks of chimeric antigen receptor (CAR) T cell infusion 4. Uncontrolled active infections 5. History of deep vein thrombosis or pulmonary embolism within six months of infusion (except for line associated deep vein thrombosis [DVT]) 6. History of stroke, unstable angina, myocardial infarction, congestive heart fa