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

Phase 1

Recruiting

• Conditions: Diffuse Large B Cell Lymphoma (DLBCL)
• Interventions: Biological: bbT369

• Registration Number: NCT05169489
• Lead Sponsor: 2seventy bio

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2021-12-11
• Study First Submitted QC: 2021-12-11
• Study First Posted: 2021-12-27
• Study Start: 2022-01-24
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-29
• Last Update Posted: 2024-04-01
• Primary Completion: 2024-08
• Study Completion: 2025-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
bbT369 Experimental Arm	bbT369	Open label, single arm treatment with bbT369

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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: Time to complete response (TCR)	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 next treatment for B Cell NHL (TTNT)	Day 1 through Month 24

Trial Locations

Locations (4)

Stanford Cancer Institute; 🇺🇸 Stanford, California, United States

Colorado Blood Cancer Institute; 🇺🇸 Denver, Colorado, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Sarah Cannon; 🇺🇸 Nashville, Tennessee, United States