Azeliragon (RAGE) + SRS posts 100% 8-wk per-patient RANO response in brain metastases

Azeliragon is an oral, brain-penetrant inhibitor of the receptor for advanced glycation end-products (RAGE) intended to dampen neuroinflammation/edema and potentially radiosensitize tumors; in the single-center Phase I/II ADORATION trial (NCT05789589) it was combined with stereotactic radiosurgery (SRS) in adults off corticosteroids ≥5 days. In Phase I (n=6 evaluable; 46 lesions ≤2 cm), dosing was 30 mg BID×6 days then 20 mg QD≥8 weeks; no DLTs occurred, neurocognitive/QoL measures remained stable, and at 8 weeks the per-patient RANO response rate was 100% (all PR), per-target-lesion RANO response was 100% (PR 95.5%, CR 4.5%), and across all treated lesions RR was 93.5% (PR 69.6%, CR 23.9%); a steroid-free cohort also showed feasibility with short follow-up (median 4.9 months). For context, SRS alone achieves high 1-yr local control (~86–94%), and peri-SRS steroids remain routine to control edema but carry neurocognitive/metabolic toxicity—so the signal here is chiefly steroid-sparing feasibility, with added-efficacy vs SRS alone unproven.