9507 Background: OBX-115 TIL are engineered to express mbIL15 under regulatory control of the small-molecule drug acetazolamide (ACZ); this engineering abrogates the need for toxic high-dose IL2 cytokine support after TIL infusion. Early data demonstrated differentiated safety and promising efficacy at the recommended phase 2 dose (RP2D; Chesney ASCO 2025). We report additional data evaluating OBX-115 in patients (pts) with advanced melanoma treated at the RP2D in the Agni-01 study. Methods: This single-arm, open-label, phase 1/2 study (NCT06060613) assesses safety, tolerability, and efficacy of the OBX-115 TIL cell therapy regimen in pts with advanced non-uveal melanoma and NSCLC (Shoushtari AACR 2025); eligibility was not restricted by LDH, HLA, or melanoma subtype. Phase 1 established an RP2D of OBX-115 1–100×10 9 cells, with ACZ 500 mg/d orally on Days 0–6 (Wk 1) and 14–20 (Wk 3). Phase 2 evaluates efficacy of the regimen at RP2D by RECIST v1.1 per investigator in pts with ≤2 prior lines of therapy. OBX-115 is manufactured from pt tumor tissue (core needle biopsy CNB or surgical excision) and infused after low-dose (Cy 750 mg/m 2 /d × 3; Flu 30 mg/m 2 /d × 4) lymphodepletion (LD). ACZ is redosed (7 d) after recovery from LD every 6 wks until Wk 24. Primary data cutoff is 19Dec2025; RECIST efficacy was updated on 22Jan2026. Results: OBX-115 was successfully manufactured (median dose 83.4×10 9 cells) and infused at RP2D schema for 15 pts with advanced melanoma progressing on/after ICI (doublet ICI in 93%); 6/8 pts (75%) with BRAF-mut disease had prior BRAF-/MEK-inhibitor exposure. 2 pts (13%) had tumor tissue procurement by CNB; 4 pts (27%) received outpatient LD. Confirmed ORR was 67% (1 CR, 9 PR, 4 SD; DCR 93%). At median study follow-up of 18.6 wks (range 10.1–73.4), median duration of response was not reached (range 4.6+ to 55.1+ wks). There was no dose-limiting toxicity, ICU transfer, or treatment-related mortality. Immune-related adverse events (AEs) included CRS (G3 n=1; G<3 n=4) and hypoxia (G3 n=1; G<3 n=2), which responded to short-course steroids; no ICANS was observed. 3 pts reported 4 OBX-115–related serious AEs. 13 pts were alive as of the datacut. Conclusions: OBX-115 TIL cell therapy at RP2D demonstrated encouraging efficacy in 2/3L advanced non-uveal melanoma, an area of unmet medical need. Unique aspects of the OBX-115 regimen, such as low-dose LD, ACZ-inducible mbIL15 expression, and CNB-enabled manufacturing, were associated with manageable side effects and compare favorably with other adoptive TIL approaches. Data support continued investigation of OBX‐115 in the ongoing phase 2 portion of Agni-01 and planned registrational study. Clinical trial information: NCT06060613 .
Betof et al. (Thu,) studied this question.
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