First-in-Human CAIX-Targeted Theranostic Pair 68Ga/177Lu-NYM096 Shows Tumor Uptake but Gastric Toxicity in Metastatic ccRCC

The study combined preclinical mouse models showing dose-dependent tumor suppression with a first-in-human component in patients who had exhausted standard therapies. 68Ga-NYM096 PET/CT demonstrated intense lesion uptake; subsequent 177Lu-NYM096 administration followed 3-plus-3 escalation, with serial planar imaging confirming biodistribution. No renal, hepatic or pancreatic toxicity occurred, yet gastric uptake produced observable toxicity, a finding that refines the risk profile beyond the original press release.

Prior small-molecule CAIX ligands such as 124I-girentuximab suffered from slower clearance and lower therapeutic indices; NYM096’s design improves pharmacokinetics while retaining specificity. This positions the pair within the expanding radiotheranostic landscape that already includes PSMA and SSTR agents, suggesting a potential niche for CAIX-positive RCC subsets unresponsive to immunotherapy combinations.

Next steps require larger multicenter dose-finding cohorts with standardized gastric protection protocols and direct comparison against cabozantinib or belzutifan. Absent randomized data, claims of survival benefit remain speculative.