ARTISTRY-6: Nemvaleukin alfa monotherapy in patients with advanced mucosal and cutaneous melanoma.

Abstract

TPS9609 Background: Despite improved outcomes for melanoma patients with the introduction of checkpoint inhibitors (CPIs), ̃50% of patients do not respond. A subset of responders ultimately progress and have limited treatment options, underscoring a high unmet need for novel treatments with durable benefit. Patients with mucosal melanoma exhibit response rates and progression-free survival times ̃2 times lower than those with cutaneous melanoma. Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel, engineered cytokine that selectively binds the intermediate-affinity interleukin-2 receptor complex to preferentially activate CD8+ T and NK cells with minimal expansion of regulatory T cells. Nemvaleukin has been granted Orphan Drug designation for the treatment of mucosal melanoma by the FDA. In ARTISTRY-1, the intravenous (IV) recommended phase 2 dose (RP2D) of 6 µg/kg nemvaleukin monotherapy demonstrated durable antitumor activity in patients with advanced melanoma, including mucosal melanoma, previously treated with a CPI. In ARTISTRY-2, the subcutaneous (SC) RP2D of 3 mg q7d was identified demonstrating pharmacodynamic effects consistent with IV delivery. Data support further evaluation of nemvaleukin monotherapy among patients with advanced mucosal and cutaneous melanoma. Methods: ARTISTRY-6 is a phase 2, global, multicenter, open-label study. Eligible patients have had prior treatment with an anti–PD-(L)1 therapy with or without anti–CTLA-4 therapy and have an ECOG performance status of 0 or 1 and adequate hematologic reserve and hepatic and renal function. Patients with advanced cutaneous (Cohort 1) and mucosal (Cohort 2) melanoma will receive nemvaleukin at the SC and IV RP2D, respectively. Patients will receive nemvaleukin until progression or intolerable toxicity. The primary objective is to evaluate the antitumor activity of nemvaleukin monotherapy defined by overall response rate. Additional objectives include the evaluation of safety, health-related quality of life, predictive biomarkers, pharmacokinetics, immunogenicity, and pharmacodynamic effects. Clinical trial information: NCT04830124.