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

October 17, 2025 updated by: Regeneron Pharmaceuticals

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)

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Former Sponsor 2seventy bio

The trial was intended to be a Phase 1/2 trial, but no participants were enrolled in Phase 2, consequently the study was terminated in Phase 1.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford Cancer Institute
    • Colorado
      • Denver, Colorado, United States, 80218
        • Colorado Blood Cancer Institute
    • Florida
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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:

    1. DLBCL (germinal center B cell [GCB] or activated B cell [ABC] type or not otherwise specified [NOS])
    2. HGBCL (with MYC and BCL2 and/or BCL6 rearrangements or NOS)
    3. PMBCL
    4. FL 3b
    5. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: bbT369 Experimental Arm
Open label, single arm treatment with bbT369
Biological: bbT369
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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
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
Time Frame: Day 1 through Month 24
Day 1 through Month 24
Phase 1: Overall Response Rate (ORR) according to the Lugano 2014 response criteria as assessed by Investigator
Time Frame: Day 1 through Month 24
Day 1 through Month 24
Phase 1: Time to response (TTR)
Time Frame: Day 1 through Month 24
Day 1 through Month 24
Phase 1: Time to complete response (TCR)
Time Frame: Day 1 through Month 24
Day 1 through Month 24
Phase 1: Time to next treatment for B Cell NHL (TTNT)
Time Frame: Day 1 through Month 24
Day 1 through Month 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Regeneron Pharmaceuticals

Investigators

  • Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 24, 2022

Primary Completion (Actual)

September 19, 2025

Study Completion (Actual)

September 19, 2025

Study Registration Dates

First Submitted

December 11, 2021

First Submitted That Met QC Criteria

December 11, 2021

First Posted (Actual)

December 27, 2021

Study Record Updates

Last Update Posted (Estimated)

October 21, 2025

Last Update Submitted That Met QC Criteria

October 17, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRC-403

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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