NATHALI‐01: A PHASE 1/2A TRIAL OF UCART20X22, AN ALLOGENEIC DUAL CAR T‐CELL THERAPY FOR PATIENTS WITH RELAPSED/REFRACTORY B‐CELL NON‐HODGKIN LYMPHOMA (NHL)

Introduction: Autologous CAR T-cell therapies have been transformative in the treatment of selected blood cancers. Despite this remarkable success, long term studies on patients treated with CD19 or CD22 T-cells revealed emergence relapses often due to antigen loss. The therapeutic options after are limited, underscoring urgent need develop novel improve current survival rates. In addition, there is a allogeneic “off-the-shelf” that readily available at time decision and overcome development limitations autologous approaches. To address these challenges, UCART20x22, first dual product candidate targeting two well-validated antigens B-cell malignancies, CD20 CD22, was generated from normal healthy donor T cells using bicistronic lentiviral construct express both CARs. TALEN® gene editing technology used inactivate TRAC CD52 genes minimize Graft-vs-Host Disease allow for use alemtuzumab (an anti-CD52 monoclonal antibody) lymphodepleting regimen. UCART20x22 displays strong activity against tumor cell lines diverse CD20/CD22 combinations, as well increased presenting targets simultaneously vitro cytotoxic proliferation assays. persists expressing (CD20, CD22) only one. pre-clinical vivo model carrying subcutaneous lymphoma tumors different combinations single mouse, provide efficient clearance one dose dependent manner. Furthermore, primary NHL patient samples levels, robust specific IFN-γ release all tested combinations. Methods: NatHaLi-01 (NCT05607420) Phase1/2a open-label dose-finding dose-expansion study evaluate safety, expansion, persistence, clinical subjects relapsed refractory B-Cell NHL. Primary endpoints tolerability, determining MTD/RP2D UCART20x22. Additional anti-lymphoma describing expansion trafficking Eligibility criteria include age 18‒80y, expression either ≥ 2 prior regimens including therapy if eligible. After lymphodepletion FCA (fludarabine 30 mg/m2 × 3d, cyclophosphamide 0.5g/m2 12 mg D1, 24 D2, D3), will receive infusion flat level ([DL]; DL1-50 106 cells, DL2-150 DL3-450x106 cells). trial currently open enrollment. research funded by: Cellectis, S.A. Keywords: aggressive non-Hodgkin lymphoma, cellular therapies, ongoing trials Conflicts interests pertinent abstract. E. Bachy Honoraria: Roche, Takeda, Kite/Gilead, BMS, Novartis, Pfizer, Incyte, ADC Therapeutics Research funding: Amgen, BMS Other remuneration: Pfizer A. Ramakrishnan Consultant advisory role AztraZeneca, Genmab, Janssen Alfonso Syros, Jazz Pharma, Astellas Abbvie, Astra Zeneca P. Riedell AbbVie, Therapeutics, Pharmacyclics, Nurix Nektar Intellia Sana Biotechnology, BeiGene, Janssen, CVS Caremark Novartis MorphoSys, CRISPR Calibr, Xencor, Fate Tessa Kite Pharma G. Cartron Onwards therapeutics, MedXcell, MabQi Jansen, Gilead, Abbvie Educational grants: Roche Barba Allogene, Kit/Gilead, Pharmaceuticals, Miltenyi Biomedicine, Pierre Fabre S. Meadows Employment leadership position: Inc. Stock ownership: LaCroce D. Thomas C. Poirot K. J. Newhall Lee M. Frattini Abramson Astra-Zeneca, Caribou Biosciences, Cellectar, Century Epizyme, Genentech, Interius, Kymera, Lilly, Morphosys, Mustang Bio, Ono Regeneron, Takeda