Less Frequent Intravenous Dosing of Nemvaleukin Alfa in Patients With Advanced Solid Tumors: The Phase 1/2 ARTISTRY-3 trial

Background Intravenous (IV) nemvaleukin alfa (nemvaleukin, ALKS 4230) administered daily on days 1-5 in 21‑day cycles demonstrated antitumor activity and manageable safety in heavily pretreated advanced solid tumors. We present results from cohort 2 of the open-label phase I/II ARTISTRY-3 (NCT04592653) study, which evaluated less frequent IV dosing of nemvaleukin in advanced solid tumors. Methods Eligible patients received escalating IV nemvaleukin doses in 21-day cycles on three schedules: day 1, days 1 and 8, and days 1 and 4. The primary endpoint was incidence of dose-limiting toxicities (DLTs). Results From April 2022 to June 2024, 52 patients received nemvaleukin. No DLTs were reported. Most nemvaleukin-related treatment-emergent adverse events (TRAEs) were grade 1-2. Six patients (12%) experienced grade 3 TRAEs, the most common being neutropenia. Nemvaleukin exposure increased with escalating doses. NK and CD8+ T-cell expansion in whole blood was observed, with minimal regulatory T-cell expansion. Nemvaleukin at 30 μg/kg on days 1 and 8 was the recommended phase II dose. No objective responses were observed; 16 (31%) patients had stable disease (6 [12%] for ≥3 months). Increased tumor microenvironment infiltration of NK and CD8+ T-cells was observed in on-treatment biopsies. Conclusion Less frequent IV doses of nemvaleukin demonstrated pharmacodynamic proof of mechanism and was tolerable with some disease stabilization.