OBX-115 (ACZ-inducible mbIL15–armored TIL) drives 67% ORR in post-ICI advanced melanoma without high-dose IL2

OBX-115 is an autologous tumor-infiltrating lymphocyte (TIL) cell therapy engineered to express membrane-bound IL15 (mbIL15) under small-molecule control with acetazolamide (ACZ), designed to avoid the traditional high-dose IL2 support used with “classic” TIL. In the single-arm Agni-01 Phase 2 cohort (NCT06060613) at the RP2D, 15 patients with advanced non-uveal melanoma progressing on/after immune checkpoint inhibitors (93% prior ICI doublet; ≤2 prior lines; 75% of BRAF-mutant patients previously received BRAF/MEK) achieved a confirmed ORR of 67% (1 CR, 9 PR) and DCR of 93%, with median DOR not reached at a median 18.6-week follow-up (range 10.1–73.4). Safety appeared differentiated for a TIL approach (low-dose Cy/Flu lymphodepletion; no DLTs/ICU/TRM; no ICANS; grade 3 CRS in 1 patient and grade 3 hypoxia in 1, both steroid-responsive); by contrast, the FDA-approved post–anti–PD-1 TIL lifileucel (Amtagvi) reported an ORR of 31.5% (n=73) in its registrational dataset, but uses non-regulatable IL2 support and more intensive inpatient-style administration in many centers.