A Phase 1/2a Study of UCART20x22 in B-Cell Non-Hodgkin Lymphoma [NatHaLi-01]

Prior treatment

• 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
• Active acute or chronic GvHD. Subjects should be off all immunosuppressive therapies for at least 6 weeks prior to start of LD
• 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
• 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
• Daily treatment with >20 mg prednisone or equivalent
• More than 4 lines of therapy R/R B-NHL, prior to start of the LD regimen
• 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)
• Positive SARS-CoV2 viral PCR test within 3 days prior to initiation of LD

Other illness

• Known hypersensitivity to any of the test materials or related compounds including murine and bovine products
• Presence of an active and clinically relevant CNS disorder
• Known active infection, or reactivation of a latent infection, whether bacterial or viral, fungal, mycobacterial, or other pathogens
• History of recurrent significant viral infection
• Inability for any reason to receive appropriate antimicrobial prophylaxis against Pneumocystis jiroveci, herpes, viruses, and invasive fungal infections
• History of hypersensitivity to alemtuzumab
• History of neutralizing anti-drug antibody against alemtuzumab
• Any known uncontrolled cardiovascular disease within 3 months of enrollment

Lab values

• Allogeneic HSCT within 3 months of the start of LD, or donor lymphocyte infusion within 6 weeks of the start of LD

Other

• Autologous HSCT infusion within 6 weeks of the start of LD
• Subjects requiring immunosuppressive treatment

• Age 18 to 80 years
• Adequate organ function (renal, liver, cardiac, pulmonary, bone marrow)
• Negative serologic or PCR test results for acute or chronic hepatitis B virus (HBV) infection
  • 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.
• Negative test result for hepatitis c virus (HCV) and human immunodeficiency virus (HIV).
• Women of childbearing potential (WOCBP) must have a negative, highly sensitive serum pregnancy test performed within 7 days prior to enrollment.
  • 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: o DLBCL o High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements o Transformed FL or transformed marginal zone lymphoma (MZL) o Follicular lymphoma Grade 3B
• R/R disease after at least 2 lines of prior treatment, which must have included: o 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 o An alkylating agent in combination with an anti-CD20 MoAb for FL o An anthracycline or bendamustine-containing chemotherapy regimen and a Bruton’s tyrosine kinase (BTK) inhibitor for mantle cell lymphoma (MCL) o 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.
• At least 1 measurable lesion according to the Lugano Response Criteria for Malignant Lymphoma
• Prior lymphoma treatment-related toxicities resolved to baseline or ≤ Grade 1 prior to start of LD regimen