relmacabtagene autoleucel as second-line therapy in adult patients with aggressive b-cell nhl

Conditions: Lymphoma, Large B-Cell, Diffuse; Follicular Lymphoma Grade 3B; High-grade B-cell Lymphoma; Mediastinal B-Cell Diffuse Large Cell Lymphoma

Summary: the primary objective of this study is to asess the efficacy of relmacabtagene autoleucel as second-line therapy in adult patients with aggressive b-cell non-hodgkins lymphoma who are ineligible for haematopoietic stem cell transplantation.

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.

Eligibility criteria:
inclusion criteria: 1. age≥18 years; 2. signed written informed consent obtained prior to any study procedures; 3. 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; 4. subjects must meet the definition of refractory or relapsed; 5. subjects were not eligible for hdct/asct based on the investigator's assessment ; 6. adequate organ function; 7. presence of positive pet assessable lesions as determined by the lugano criteria ; 8. eastern cooperative oncology group (ecog) performance status of 0-2; 9. expected survival greater than 12 weeks; 10. adequate vascular access for leukapheresis procedure; 11. 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: 1. subjects with non-hodgkin's lymphoma who have received second or more line therapy; 2. lymphoma of the primary center (subjects with secondary central nervous system lymphoma are allowed to enroll; 3. history of another primary malignancy that has not been in remission for at least 2 years; 4. subjects has active hbv, hcv, hiv or syphilis infection at the time of screening; 5. deep venous thrombosis (dvt)/pulmonary embolism (pe), or dvt/pe requires anti-coagulation within 3 months prior to signing the icf; 6. subjects with uncontrolled systemic fungal, bacterial, viral or other infection; 7. uncontrolled diabetes and hypertension; 8. presence of acute or chronic graft-versus-host disease (gvhd); 9. active autoimmune disease requiring immunosuppressive therapy; 10. history of any serious cardiovascular disease or presence of clinically relevant cns pathology; 11. pregnant or nursing women; 12. subjects received an autologous or allogeneic hematopoietic stem cell transplant; 13. uncontrolled conditions or unwillingness or inability to follow the procedures required in the protocol; 14. received car t-cell or other genetically-modified t-cell therapy previously; 15. received live vaccination within 6 weeks prior to lymphocyte clearance chemotherapy; 16. history of severe hypersensitivity reactions to any of the drug ingredients used in this study product.

Keywords: relmacabtagene autoleucel aggressive b-cell non-hodgkin lymphoma chimeric antigen receptor t cells second-line