Trial to Determine the Efficacy and Safety of JCAR017 in Adult Participants With Aggressive B-Cell Non-Hodgkin Lymphoma (TRANSCENDWORLD)

Trial to Determine the Efficacy and Safety of JCAR017 in Adult Participants With Aggressive B-Cell Non-Hodgkin Lymphoma

A Phase 2, Single-arm, Multi-center Trial to Determine the Efficacy and Safety of JCAR017 in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma or With Other Aggressive B-Cell Malignancies

The purpose of this study is to evaluate the efficacy and safety of JCAR017 in participants with aggressive B-cell non-Hodgkin lymphoma (B-NHL)

This is a study to determine the efficacy and safety of JCAR017 in adult participants with aggressive B-cell NHL. The study will enroll participants in Europe and Japan with diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS; de novo or transformed follicular lymphoma [tFL]), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (HGBL), follicular lymphoma Grade 3B (FL3B), and primary central nervous system lymphoma (PCNSL). Participants with secondary central nervous system (CNS) involvement are allowed. Once enrolled, participants will undergo leukapheresis to enable JCAR017 cell product generation. Upon successful JCAR017 cell product generation, participants will receive lymphodepleting chemotherapy followed by infusion of JCAR017. JCAR017 will be administered by intravenous infusion. Participants will be followed for approximately 2 years after their JCAR017 infusion for safety, disease status, survival and health-related quality of life. Delayed adverse events following exposure to gene modified T cells will be assessed and long-term persistence of these modified T cells will continue to be monitored under a separate long-term follow-up protocol for up to 15 years after JCAR017 infusion as per competent authority guidelines.

Non-Hodgkin lymphoma, Aggressive B-cell non-Hodgkin lymphoma, Diffuse large B-cell lymphoma, Relapse / refractory lymphoma, Transplant not eligible, High-grade B-cell lymphoma, Primary central nervous system lymphoma, Transformed follicular lymphoma, Follicular lymphoma Grade 3B, JCAR017, Liso-Cel

Overall Response Rate (ORR) of JCAR017 in participants with Non-Hodgkin Lymphoma (NHL; including secondary central nervous system (CNS) involvement)

ORR of JCAR017 in participants with relapsed/refractory (r/r) primary central nervous system lymphoma (PCNSL)

Pharmacokinetics by quantitative polymerase chain reaction (qPCR) - Maximum plasma concentration of drug (Cmax)

Patient-Reported Outcomes - European Organization for Research and Treatment of Cancer - Quality of Life C30 questionnaire

Patient-Reported Outcomes - Functional Assessment of Cancer Therapy-Lymphoma "Additional concerns" subscale

Inclusion Criteria: Histological confirmation of diagnosis at last relapse Adequate organ function Adequate vascular access for leukapheresis procedure Exclusion Criteria: Prior history of malignancies, other than aggressive relapsed/refractory Non-Hodgkin Lymphoma, unless the participant has been in remission for ≥ 2 years with the exception of non-invasive malignancies Received previous CD19-targeted therapy Progressive vascular tumor invasion, thrombosis, or embolism Other protocol-defined inclusion/exclusion criteria apply

Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.