First in human evaluation of a no alpha interleukin 2 mutein safety and preliminary pharmacodynamic and clinical effect summary

This PACUPod episode reviews a first-in-human study of a no-alpha IL-2 mutein in adults with advanced solid tumors refractory to standard therapies. The Phase I, single-arm, dose-escalation trial (13 patients) assessed safety, tolerability, pharmacodynamics, and preliminary clinical activity across escalating doses (300–2400 IU/kg). Key findings include no maximum tolerated dose and the absence of vascular leak syndrome, with one serious adverse event (ventricular dysfunction and pneumonitis) possibly drug-related. Pharmacodynamically, treatment expanded CD8+ T cells and natural killer (NK) cells while avoiding regulatory T cell (Treg) expansion, indicating selective immune activation. The episode discusses implications for clinical practice, dosing optimization, potential drug interactions, and the study’s limitations (small sample size, single-arm design) along with directions for future randomized trials to confirm efficacy and safety.