Study Evaluating UCART20x22 in B-Cell Non-Hodgkin Lymphoma

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).

Inclusion Criteria:Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1Relapsed or refractory (R/R) mature B-NHL per 2016 WHO criteria and positive for CD20 and/or CD22Subjects 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 3BR/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)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 regimenPrevious 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 regimenPrior MoAb therapy (approved or investigational) within 30 days prior to start of LDPrior systemic immunostimulatory agent within 3 half-lives prior to start of the LD regimenPrior cell or gene therapy (approved or investigational) within 6 weeks of the start of LDPrior cell or gene therapy (approved or investigational) targeting both CD20 and CD22Autologous HSCT infusion within 6 weeks of the start of LDAllogeneic HSCT within 3 months of the start of LD, or donor lymphocyte infusion within 6 weeks of the start of LDSubjects should be off all immunosuppressive therapies for at least 6 weeks prior to start of LDRadiotherapy within 8 weeks (except for palliative radiotherapy for specific on-target lesions) (prior to start of LD regimen)Active acute or chronic graft versus host diseaseEvidence of active central nervous system (CNS) lymphoma or previous CNS involvement of R/R B-NHLPresence of an active and clinically relevant CNS disorderDaily treatment with >20 mg prednisone or equivalentKnown active infection, or reactivation of a latent infection, whether bacterial or viral, fungal, mycobacterial, or other pathogensHistory of hypersensitivity to alemtuzumabHistory of neutralizing anti-drug antibody against alemtuzumabAny known uncontrolled cardiovascular disease within 3 months of enrollmentSubjects requiring immunosuppressive treatmentMajor surgery within 28 days prior to start of LDEvidence 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)