CTIM-23. FIRST-IN-HUMAN IMMUNOTHERAPY TARGETING LYMPHOPENIA IN RECURRENT GLIOBLASTOMA MULTIFORM (GBM): NAI AND PD-L1 T-HANK PLUS BEVACIZUMAB WITH COMPLETE RESPONSE

Abstract BACKGROUND Treatment options for recurrent GBM are limited and associated with high mortality. We hypothesize that current standards of care for GBM induce severe lymphopenia, and by treating lymphopenia (activating NK & T-cells, lymphocytes key to immunogenic cell death), overall survival may be prolonged. Anktiva (nogapendekin alfa-inbakicept, NAI), an IL-15 receptor superagonist, is the first treatment to address lymphopenia by proliferating NK and T-cells. Administered in combination with PD-L1 targeted high-affinity CAR-NK cells (PD-L1 t-haNK) and bevacizumab, treating lymphopenia was hypothesized to elicit tumor response in recurrent GBM METHODS Phase I QUILT-3.078 trial of participants with GBM (IDH WT) who recurred after surgery and temozolomide/XRT. Twelve participants received PD-L1 t-haNK, NAI and bevacizumab, every two weeks, as outpatients. Three patients also received concurrent tumor treating fields. RESULTS At June 4, 2025 data cutoff, 12 participants have received 57 total doses, with 7/12 (58.3%) remaining on therapy. One participant has ongoing radiographic complete response after four doses. In this participant, the Absolute lymphocyte count (ALC) level increased from 170 lymphocytes/µL on entry to ≥1,000 lymphocytes/µL during study treatment and has been maintained. In eight evaluable participants, ALC trend increased from baseline through cycle 4 and was maintained. Median follow-up is 79 days with two deaths on-study, median OS is not reached. Five patients had any SAE, of which one was suspected to be related to bevacizumab (pulmonary embolism), and no SAEs were related to experimental therapy. No CRS or ICANS was observed. CONCLUSIONS These findings provide support that treating lymphopenia and reconstituting lymphocytes (NK & T cells) results in potential OS benefit. This is the first report of disease response in participants with refractory GBM who received orchestrated temporal immunotherapy with CAR-NK cells combined with an IL-15 receptor superagonist and bevacizumab to treat lymphopenia. Updated data to be presented.