a study of bbt369 in relapsed and/or refractory b cell non-hodgkin's lymphoma (nhl)

Conditions: Diffuse Large B Cell Lymphoma (DLBCL)

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.

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.

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