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 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
• > 4 lines of therapy R/R B-NHL 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 months 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)