Relmacabtagene Autoleucel As Second-Line Therapy in Adult Patients with Aggressive B-cell NHL

This is an open-label, multicenter, Phase 2 study to determine the antitumor activity, PK, and safety of JWCAR029(Relmacabtagene autoleucel ) in subjects who have relapsed within 12 months from, or are refractory to, a single line of immunochemotherapy for aggressive Bcell NHL and are ineligible for HSCT (as defined in the eligibility criteria). Subjects will be treated with lymphodepleting chemotherapy and JWCAR029.

Inclusion criteria

• Age≥18 years;
• Signed written informed consent obtained prior to any study procedures;
• Histologically confirmed relapsed or refractory (R/R) aggressive B-cell NHL of the following histologiesLBCL as defined by the World Health Organization (WHO) Classification 2022:Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), high-grade B-cell lymphoma (HGL) with MYC and BCL2 rearrangements,HGL-NOS, Primary mediastinal large B-cell lymphoma, Follicular lymphoma Grade 3B (FL3B),Indolent B-NHL-transformed large B-cell lymphoma with adequate prior treatment with anthracycline-containing agents and rituximab or other CD20-targeted agents;
• Subjects must meet the definition of refractory or relapsed;
• Subjects were not eligible for HDCT/ASCT based on the investigator's assessment ;
• Adequate organ function;
• Presence of positive PET assessable lesions as determined by the Lugano criteria ;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
• Expected survival greater than 12 weeks;
• Adequate vascular access for leukapheresis procedure;
• Women of childbearing potential must agree to use highly effective methods of contraception for at least 28 days prior to lymphocyte clearance chemotherapy through 2 year after Relmacabtagene Autoleucel infusion; Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method for 2 year after Relmacabtagene Autoleucel infusion;

Exclusion criteria

• Subjects with non-Hodgkin's lymphoma who have received second or more line therapy;
• Lymphoma of the primary center (subjects with secondary central nervous system lymphoma are allowed to enroll;
• History of another primary malignancy that has not been in remission for at least 2 years;
• Subjects has active HBV, HCV, HIV or syphilis infection at the time of screening;
• Deep venous thrombosis (DVT)/Pulmonary embolism (PE), or DVT/PE requires anti-coagulation within 3 months prior to signing the ICF;
• Subjects with uncontrolled systemic fungal, bacterial, viral or other infection;
• Uncontrolled diabetes and hypertension;
• Presence of acute or chronic graft-versus-host disease (GVHD);
• Active autoimmune disease requiring immunosuppressive therapy;
• History of any serious cardiovascular disease or presence of clinically relevant CNS pathology;
• Pregnant or nursing women;
• Subjects Received an autologous or allogeneic hematopoietic stem cell transplant;
• Uncontrolled conditions or unwillingness or inability to follow the procedures required in the protocol;
• Received CAR T-cell or other genetically-modified T-cell therapy previously;
• Received live vaccination within 6 weeks prior to lymphocyte clearance chemotherapy;
• History of severe hypersensitivity reactions to any of the drug ingredients used in this study product.