study evaluating ucart20x22 in b-cell non-hodgkin lymphoma

Conditions: B-cell Non-Hodgkin Lymphoma (B-NHL)

Summary: first-in-human, open-label, dose-finding and dose-expansion study of ucart20x22 administered intravenously in subjects with relapsed or refractory b-cell non-hodgkin lymphoma (b-nhl). the purpose of this study is to evaluate the safety and clinical activity of ucart20x22 and determine the maximum tolerated dose (mtd) and recommended phase 2 dose (rp2d).


Eligibility criteria:
inclusion criteria: * eastern cooperative oncology group (ecog) performance status of 0 or 1 * relapsed or refractory (r/r) mature b-nhl per 2016 who criteria and positive for cd20 and/or cd22 * subjects with nhl subtypes defined by who: * -dose-finding part: r/r mature b-nhl (except chronic lymphocytic leukemia/small lymphocytic leukemia \[cll/sll\], richter's transformation from prior cll/sll, burkitt's lymphoma, and waldenstrom's macroglobulinemia) * -dose-expansion part: r/r lbcl, defined as: i. dlbcl; ii. high-grade b-cell lymphoma with myc and bcl2 and/or bcl6 rearrangements; iii. transformed fl or transformed marginal zone lymphoma (mzl); iv. follicular lymphoma grade 3b * r/r disease after at least 2 lines of prior treatment, which must have included: * -an anti-cd20 moab and an anthracycline for dlbcl, high-grade b-cell lymphoma with myc and bcl2 and/or bcl6 rearrangements, primary mediastinal large b-cell lymphoma (pmbcl), or transformed fl or mzl * -an alkylating agent in combination with an anti-cd20 moab for fl * -an anthracycline or bendamustine-containing chemotherapy regimen and a bruton's tyrosine kinase (btk) inhibitor for mantle cell lymphoma (mcl) * -autologous anti-cd19 car t-cell therapy, if approved and available for the indicated lymphoma subtype, unless the subject is unable or is ineligible to receive approved autologous anti-cd19 car t-cell therapy (e.g., fail leukapheresis or manufacture, unable to wait for manufacture, cd19 negative disease, etc.) * autologous hematopoietic stem cells must be available prior to the start of the ld regimen if the subject is considered high-risk for prolonged hematologic toxicity exclusion criteria: * prior use of an investigational product (except for cell or gene therapies and moabs) within 5 half-lives or within 14 days, whichever is shorter, prior to start of ld regimen * previous approved therapy including chemotherapy, biologic (except moabs), or targeted therapy for r/r b-nhl with 5 half-lives or within 14 days, whichever is shorter, prior to start of the ld regimen * prior moab therapy (approved or investigational) within 30 days prior to start of ld * prior systemic immunostimulatory agent within 3 half-lives prior to start of the ld regimen * prior cell or gene therapy (approved or investigational) within 6 weeks of the start of ld * prior cell or gene therapy (approved or investigational) targeting both cd20 and cd22 * autologous hsct infusion within 6 weeks of the start of ld * allogeneic hsct within 3 months of the start of ld, or donor lymphocyte infusion within 6 weeks of the start of ld * active acute or chronic graft versus host disease (gvhd). subjects should be off all immunosuppressive therapies for at least 6 weeks prior to start of ld * radiotherapy within 8 weeks (except for palliative radiotherapy for specific on-target lesions) (prior to start of ld regimen) * evidence of active central nervous system (cns) lymphoma or previous cns involvement of r/r b-nhl * presence of an active and clinically relevant cns disorder * daily treatment with \>20 mg prednisone or equivalent * known active infection, or reactivation of a latent infection, whether bacterial or viral, fungal, mycobacterial, or other pathogens * history of hypersensitivity to alemtuzumab * history of neutralizing anti-drug antibody against alemtuzumab * any known uncontrolled cardiovascular disease within 3 months of enrollment * subjects requiring immunosuppressive treatment * major surgery within 28 days prior to start of ld * evidence of another uncontrolled malignancy within 2 years prior to screening (except in situ nonmelanoma skin cell cancers and/or carcinoma in-situ of the cervix)

Keywords: b-cell non-hodgkin lymphoma (b-nhl) relapsed/refractory b-nhl universal chimeric antigen receptor t-cell (ucar-t) therapy allogeneic transcription activator-like effector nuclease (talen®)