ARTISTRY-3: Effect of nemvaleukin alfa with a less frequent IV dosing schedule as monotherapy and in combination with pembrolizumab and impact on the tumor microenvironment (TME) in patients (pts) with advanced solid tumors.

Abstract

TPS2684 Background: Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel engineered cytokine that selectively binds the intermediate-affinity interleukin-2 (IL-2) receptor, preferentially activating and expanding antitumor CD8+ T cells and NK effector cells, with minimal effect on regulatory T cells. Nemvaleukin was designed to leverage antitumor effects of the IL-2 pathway while limiting typical IL-2‒associated toxicity. In ARTISTRY-1, the recommended phase 2 dose (RP2D) for nemvaleukin monotherapy of 6 µg/kg IV on days 1 to 5 of a 21-day cycle elicited durable and deep responses in pts with advanced melanoma and renal cell carcinoma (Boni et al. ASCO 2021:abstr 2513). Responses with nemvaleukin plus pembrolizumab were also observed in platinum-resistant ovarian, breast, cervical, gastrointestinal, and genitourinary cancers. ARTISTRY-3 will investigate the effects of nemvaleukin as monotherapy and in combination with pembrolizumab on the TME in pts with advanced solid tumors, and in an additional cohort (Cohort 2), to further assess a less frequent IV dosing schedule for nemvaleukin. Methods: The phase 1/2, open-label ARTISTRY-3 (NCT04592653) study will enroll adults (≥18 years) with select advanced solid tumors, ≥1 accessible lesion for biopsy, ≥1 target lesion (per RECIST v1.1), ECOG PS of 0 or 1, estimated life expectancy of ≥3 months, adequate hematologic reserve, and adequate hepatic and renal function. Primary objectives: to evaluate effects of nemvaleukin monotherapy on the TME (Cohort 1) and to determine RP2D for less frequent dosing schedule (Cohort 2). Additional objectives are to evaluate: efficacy, safety, immunogenicity, and pharmacokinetics of nemvaleukin monotherapy; effects of nemvaleukin plus pembrolizumab on the TME; and correlative biomarkers of nemvaleukin as monotherapy and combination. Following the protocol amendment, additional pts enrolled in Cohort 1 will receive lead-in monotherapy at a dose selected based on results from Cohort 2, and pre- and on-treatment biopsies will be collected for TME assessments. Subsequent cycles will be administered in combination with pembrolizumab, and a biopsy may be collected at cycle 4 or 5. Tumor types eligible for Cohort 2 are selected based on activity observed in the ARTISTRY-1 study. A quantitative system pharmacology model was applied to identify a less frequent schedule for nemvaleukin monotherapy and combination. Cohort 2 will initially assess safety and tolerability of nemvaleukin at 1 dose per 21-day cycle. Two doses per 21-day cycle may be implemented to achieve optimal PK/PD parameters. Bayesian optimal interval design methodology with open enrollment will be applied to facilitate dose escalation decisions. Clinical trial information: NCT04592653.