Clinical trial NCT05169489: A Study of bbT369 in Relapsed and/or Refractory B Cell Non-Hodgkin's Lymphoma (NHL)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-12-27
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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: Former Sponsor 2seventy bio

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1: Incidence of safety events including: adverse events (AEs), adverse events of special interest (AESIs), and dose limiting toxicities (DLTs)
timeFrame: Day 1 through Month 24
Secondary outcomes:
measure: 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
timeFrame: Day 1 through Month 24
measure: Phase 1: Overall Response Rate (ORR) according to the Lugano 2014 response criteria as assessed by Investigator
timeFrame: Day 1 through Month 24
measure: Phase 1: Time to response (TTR)
timeFrame: Day 1 through Month 24
measure: Phase 1: Time to complete response (TCR)
timeFrame: Day 1 through Month 24
measure: Phase 1: Time to next treatment for B Cell NHL (TTNT)
timeFrame: Day 1 through Month 24
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Cancer Institute
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Nashville
country: United States
facility: Sarah Cannon
state: Tennessee
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: