Background: CB-010 is an allogeneic anti-CD19 CAR-T cell therapy derived from healthy donor T cells using CRISPR hybrid RNA-DNA (chRDNA) technology. This technology is used to introduce 3 genome edits: (1) knockout of TRACto eliminate TCR expression and reduce risk of GvHD, (2) insertion of a CD19-specific CAR (scFv FMC63) into theTRAC locus, and (3) knockout of PD-1 to prevent premature CAR-T cell exhaustion and potentially enhance antitumor activity. Methods: ANTLER is a Phase 1 clinical trial (NCT04637763) with a 3+3 dose escalation phase and a dose expansion phase designed to evaluate safety, tolerability, and antitumor activity of CB-010 in patients (pts) with r/r B-NHL and determine RP2D. In dose escalation, pts must have received ≥2 prior lines of chemoimmunotherapy or had primary refractory disease to 1L therapy. Pts received lymphodepletion with sequential cyclophosphamide (60 mg/kg/day x 2 days) and fludarabine (25 mg/m2/day x 5 days) followed by a single CB-010 infusion. Results: 16 pts with r/r B-NHL (10 LBCL, 3 MCL, 2 FL with POD24, 1 MZL) received CB-010 at 40 x 10⁶ CAR-T cells (dose level 1; N=8), 80 x 10⁶ CAR-T cells (dose level 2; N=5), or 120 x 10⁶ CAR-T cells (dose level 3; N=3) during dose escalation. Median age was 66 years (range 55-82). Median time since first diagnosis was 2.4 years (range 0.2-16.4). Median prior lines of therapy was 2 (range 1-8). CB-010 was generally well tolerated. No GvHD was seen. CRS occurred in 7/16 (44%) pts (no CRS grade ≥3). Median time to CRS onset was 3.5 days and median duration was 3 days. ICANS occurred in 4/16 (25%) pts (13% grade ≥3). Median time to ICANS onset was 7.5 days and median duration was 2 days. The 3 most common TEAEs grade ≥3 were thrombocytopenia (11/16; 69%), neutropenia (9/16; 56%), and anemia (8/16; 50%). One grade 3 infection (antecubital cellulitis) occurred unrelated to CB-010. After a single CB-010 infusion, 15/16 (94%) pts achieved an overall response, 11/16 (69%) achieved a CR, and 7/16 (44%) achieved a CR at ≥6 months. Median time to CR was 28 days. Among LBCL pts (n=10), 9 (90%) achieved an overall response, 7 (70%) achieved a CR, and 5 (50%) achieved a CR at ≥6 months. To date,2 pts have completed the 24-month study period with ongoing CR. Peak expansion of CB-010 occurred at days 7-10 post-infusion. T and NK cells recovered rapidly in peripheral blood (<3 weeks) after lymphodepletion, and B cells remained below the limit of quantification beyond 3 months, supporting specific targeting of B cells by CB-010. Conclusions: CB-010 showed a manageable safety profile and promising efficacy for treatment of pts with r/r B-NHL, including aggressive subtypes. The dose escalation phase is complete. Enrollment of 2L LBCL pts in dose expansion is ongoing. Initial dose expansion data at the CB-010 RP2D and translational data will be presented for the first time at the meeting. Clinical trial information: NCT04637763.