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

NCT05169489 | Terminated Phase 1 FDA Drug

• 1 other identifier: CRC-403
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 4

Brief Summary

This non-randomized, open label, multi-site, 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). A long-term follow-up (LTF-01 \[NCT06798298\]) 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.

Conditions

Diffuse Large B Cell Lymphoma (DLBCL)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

Study Arms (1)

bbT369 Experimental Arm

EXPERIMENTAL

Open label, single arm treatment with bbT369

Biological: bbT369

Interventions

bbT369 BIOLOGICAL

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.

bbT369 Experimental Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (4)

Stanford Cancer Institute

Stanford, California, 94305, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Sarah Cannon

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma; Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2021
• First Posted: December 27, 2021
• Study Start: January 24, 2022
• Primary Completion: September 19, 2025
• Study Completion: September 19, 2025
• Last Updated: October 21, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

US (4)