A Study of bbT369 in Relapsed and/or Refractory B Cell Non-Hodgkin's Lymphoma (NHL)

Study Overview
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Brief Summary
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A Phase 1/2 Study of bbT369, a dual targeting CAR T cell drug product with a gene edit, in Relapsed and/or Refractory B cell Non-Hodgkin's Lymphoma.

Detailed Description
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This is a non-randomized, open label, multi-site Phase 1/2 study. This first-in-human Phase 1/2 Study CRC-403 will evaluate the safety and efficacy of bbT369 in subjects with relapsed and/or refractory B cell non-Hodgkin's lymphoma (NHL). Phase 1 will be a dose escalation, up to a planned four dose levels. After establishing MTD, Phase 2 will enroll subjects with B cell NHL in 2 cohorts: CAR T exposed subjects (Cohort 1) and CAR T naïve subjects (Cohort 2). A long-term follow-up is planned, in which subjects who received bbT369 will be followed for up to 15 years after drug product infusion to evaluate for safety and continued efficacy.

Official Title
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A Phase 1/2 Study of bbT369, a Dual Targeting CAR T Cell Drug Product With a Gene Edit, in Relapsed and/or Refractory B Cell Non-Hodgkin's Lymphoma (NHL)

Conditions
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Diffuse Large B Cell Lymphoma (DLBCL)

Intervention / Treatment
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* Biological: bbT369


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years of age at the time of signing informed consent. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. Diagnosis of B-cell NHL according to WHO 2017 classification or WHO 2016 classification where applicable: DLBCL (germinal center B cell [GCB] or activated B cell [ABC] type or not otherwise specified [NOS]) HGBCL (with MYC and BCL2 and/or BCL6 rearrangements or NOS) PMBCL FL 3b DLBCL transformed from FL Participants must have relapsed or refractory (r/r) B cell NHL after autologous stem cell transplant (ASCT) or at least 2 prior lines of therapy including an anti-CD20 monoclonal antibody and an anthracycline containing chemotherapy regimen. Note: participants with DLBCL transformed from FL must have r/r disease after ASCT or at least 2 prior therapies following transformation irrespective of therapeutic agents. At least 1 FDG-avid lesion per Lugano Classification criteria at time of enrollment. Exclusion Criteria: Treatment with any investigational cellular therapy prior to enrollment. Treatment with an approved anti-CD19 CAR T cell therapy in an investigational setting may be permitted after discussion with and approval of the Sponsor. Progression within 6 weeks of prior anti-CD19 CAR T cell therapy. Residual toxicities or end-organ damage to vital organs from prior therapy that could put a subject at undue risk based on Investigator's assessment. Toxicities related to prior cytokine release syndrome (CRS) or neurotoxicity must be resolved. If a subject has received prior anti-CD19 CAR T therapy, development of ≥ Grade 3 CAR T related CRS or ≥ Grade 3 neurotoxicity that in the opinion of the Investigator would cause unacceptable risk of toxicity to the subject upon treatment with bbT369. Primary central nervous system (CNS) lymphoma or a history or presence of clinically relevant CNS pathology. Active autoimmune disease requiring systemic immunosuppressive and/or cytotoxic therapy within the past two years. Treatment with any prior anti-CD79a therapy. Previous history of an allogeneic bone marrow transplantation. Autologous stem cell transplantation (ASCT) is permitted.

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: bbT369 Experimental Arm<br>Open label, single arm treatment with bbT369 | Biological: bbT369<br>* bbT369 is a genetically modified autologous T cell immunotherapy product consisting of T cells that are transduced with a single lentiviral vector (LVV) to express anti-CD79a and anti-CD20 chimeric antigen receptors (CARs) and transfected with an mRNA encoding the CBLB-targeting megaTAL enzyme to edit the CBLB gene, suspended in a cryopreservative solution.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Incidence of safety events including: adverse events (AEs), adverse events of special interest (AESIs), and dose limiting toxicities (DLTs) |  | Day 1 through Month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Rates of disease-specific response criteria including complete response rate(CRR), partial response rate(PRR), stable disease rate(SDR), and progressive disease rate(PDR) according to the Lugano 2014 response criteria as assessed by Investigator |  | Day 1 through Month 24 | 
| Phase 1: Overall Response Rate (ORR) according to the Lugano 2014 response criteria as assessed by Investigator |  | Day 1 through Month 24 | 
| Phase 1: Time to response (TTR) |  | Day 1 through Month 24 | 
| Phase 1: Time to complete response (TCR) |  | Day 1 through Month 24 | 
| Phase 1: Time to next treatment for B Cell NHL (TTNT) |  | Day 1 through Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR T, CART, CAR-T, Cell therapy, Lymphoma, Diffuse large B cell lymphoma (DLBCL), Primary mediastinal (thymic) large B cell lymphoma (PMBCL), High-grade B cell lymphoma (HGBCL), Follicular lymphoma (FL) 3b, DLBCL transformed from FL, NHL, Non hodgkin's, Dual targeting, Gene edit, T cell, CD20, CD79a, CBLB, Non-hodgkin's, Non-hodgkin