Background: All the FDA-approved CD19 CAR-T products are based on FMC63 scFv, which binds to the membrane-distal region of CD19. We developed a novel anti-CD19 antibody clone (1218) that binds to a membrane-proximal epitope of CD19, thereby not competing with FMC63. AT101 is an autologous CAR T cell transduced with a lentiviral vector, including the CD19-CAR with a humanized scFv of 1218, 4-1BB costimulatory, and CD3zeta domain. Methods: In this phase 1 trial, patients (n = 3 per dose level; up to n = 18 in total) are treated with AT101 in 3 dose-escalation cohorts based on a standard 3 + 3 design. Each patient received a single intravenous dose of AT101 at dose level (DL) 1 (0.2 x 10⁶ cells/kg), DL2 (1.0 x 10⁶ cells/kg), or DL3 (5.0 x 10⁶ cells/kg). The primary objective is to determine the safety, the maximum tolerated dose (MTD), and the recommended phase 2 dose (RP2D) of AT101. The secondary objective is to evaluate the pharmacokinetics of AT101 and the preliminary efficacy, such as overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), event-free survival (EFS), and overall survival (OS). Key eligibility criteria include patients aged ≥19 with histologically confirmed relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). Results: Fourteen patients were enrolled from March 2022 to December 2022, and nine were treated. The median age of treated patients was 61.6 years (ranged from 39 to 84) after a median of 4 prior lines of therapy (range 2-10). Their subtypes of NHL were as follows: diffuse large B cell lymphoma (n = 4), follicular lymphoma (n = 3), mantle cell lymphoma (n = 1), or marginal zone lymphoma (n = 1). The dosing of AT101 at DL1 and DL2 was completed. The dosing at DL3 is ongoing. Across cohorts 1 and 2, no grade 3 or higher cytokine release syndrome (CRS) was reported. Among the first three patients at DL1, one dose-limiting toxicity (DLT) of grade 4 neurotoxicity was observed but resolved in a week without sequelae. No other DLTs were observed in the additional three patients at the DL1 and three at the DL2 cohort. Another one at DL2 experienced grade 1 CRS with grade 1 neurotoxicity. Five patients experienced Grade ≥3 hematologic toxicities. An ORR is 66.7% (4/6) in cohort 1 and 100% (3/3) in cohort 2, including six complete responses (CR, 50.0% [3/6] in cohort 1 and 100% [3/3] in cohort 2). As of February 13, 2023, all six CRs are ongoing, including two patents exceeding six months after the treatments. Updated results will be presented at the meeting, including the cohort of DL3. Conclusions: In this phase I study, AT101 was well tolerated at the first two dose levels and showed promising efficacy in relapsed or refractory B-cell NHL patients. The majority of adverse effects were transient and manageable. The administrations of DL3 are currently ongoing, and updated results will be presented at the meeting. Clinical trial information: NCT05338931.