Issues

Bentebibel, Hurwitz, Bernatchez, and colleagues report a first-in-human phase I study to evaluate the safety and activity of NKTR-214 (bempegaldesleukin), a human recombinant IL2 conjugated to slowly releasable polyethylene glycol chains that bias binding to the intermediate-affinity IL2Rβγ complex instead of the low-affinity IL2Rα chain. In heavily pretreated patients with advanced solid tumors, NKTR-214 was well tolerated, and the best overall response was stable disease in 14 of 26 evaluable patients (54%). NKTR-214 treatment induced activation and proliferation of immune cells in peripheral blood, and comparison of baseline and on-treatment tumor biopsies revealed that NKTR-214 increased T-cell activation signatures, CD8⁺ T-cell infiltration, and T-cell clonality. These findings suggest that NKTR-214 not only has immunostimulatory activity but may be a safer alternative to high-dose unconjugated IL2, making it an attractive candidate for combination immunotherapy strategies. For details, please see the article by Bentebibel, Hurwitz, Bernatchez, and colleagues on page 711.