Background: AB-101 is a non-genetically modified, cord blood-derived, allogeneic, cryopreserved, NK cell therapy for use in combination with monoclonal antibody (mAb) or innate cell engager therapies. AB-101 is being developed to enhance response to mAb therapy through the antibody-dependent cellular cytotoxicity (ADCC) mechanism. Many cancer patients (pts) are unable to mount a robust ADCC response, rendering mAb therapy less effective for these pts. AB-101 has attributes that enhance NK cell activity: Consistent phenotype for tumor engagement and cytotoxicity; Selected killer immunoglobulin-like receptor B (KIR B) haplotype; V/V CD16 polymorphism at F158 for enhanced ADCC. AB-101 outpatient administration provides optimized NK cells to pts, potentially enhancing their anti-tumor activity in combination with mAb that utilize the ADCC mechanism. We have initiated a Ph 1/2 clinical trial evaluating the combination of AB-101 with rituximab (RTX) in pts with R/R NHL of B-cell origin. Methods: Two AB-101 dose levels, 1 or 4e9 cells, will be evaluated as monotherapy or combination with RTX. All enrolled pts will receive at least 1 cycle of 4 weekly AB-101 doses, with cyclophosphamide/fludarabine lymphodepletion (LD). Pts receiving the combination may receive up to 4 treatment cycles. Results: Dose escalation is ongoing with 17 pts enrolled. Pts were elderly (median of 68 yrs) and heavily pretreated (median of 4 prior lines) with 64% having had prior CD19 CAR-T. Pts had DLBCL (9), FL (5), MCL (2), and LPL/WM (1). 11 monotherapy pts and 6 RTX combination pts were treated at time of abstract. 16 pts received AB-101 at 1e9 cells/dose; 1 pt received 4e9 cells/dose. 4 of 6 combination pts have received > 1 cycle. AB-101 was generally well tolerated. The most common G3+ AEs were LD-related neutropenia and lymphopenia. All AB-101 related AEs were G1/2. ICANs and GVHD, events associated with allogeneic cell therapy, were not reported; Gr 1 CRS occurred in 2 pts and resolved within 24h. SAEs were reported in 9 pts. The most common SAEs were associated with either infections (n = 3) or PD (n = 3) and one related SAE of Gr 1 fever was reported. No pts discontinued treatment due to an AB-101-related AE. ORR for the RTX cohort was 67% (4/6) with a CR rate of 50% (3/6). 3 of 4 responses were observed in pts who failed prior CAR-T therapy. ORR for the monotherapy cohorts was 27% (3/11). Conclusions: 4 weekly doses of AB-101 given alone or with RTX appeared to be safe and well tolerated without the serious/severe toxicities associated with CAR-T therapies. Preliminary efficacy of the combination treatment is encouraging. The study is ongoing and continues to enroll the combination cohorts and the 4e9 cells/dose level. Updated safety, efficacy, and exploratory PK/PD/immunogenicity results will be provided during the presentation. Clinical trial information: NCT04673617.