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

Abstract

TPS9592 Background: Despite improved outcomes in melanoma 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 ≈2 times lower than those with cutaneous melanoma. Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel, engineered cytokine that selectively binds to the intermediate-affinity interleukin-2 receptor complex to preferentially activate CD8+ T and natural killer cells, with minimal expansion of regulatory T cells. Nemvaleukin has been granted Orphan Drug designation for the treatment of mucosal melanoma by the US FDA. In the ARTISTRY-1 study, the intravenous (IV) recommended phase 2 dose (RP2D) for nemvaleukin monotherapy (6 µg/kg on days 1-5 of a 21-day cycle) demonstrated durable antitumor activity in patients with advanced melanoma, including mucosal melanoma, previously treated with a CPI (N = 46, overall response rate [ORR] 13.0% [95% CI 4.9-26.3], median duration of response 8.1 weeks [range 6.1-79.0]). In the ARTISTRY-2 study, the subcutaneous (SC) RP2D was identified as 3 mg every 7 days, which demonstrated pharmacodynamic effects consistent with those of IV delivery. Data from these studies support further evaluation of nemvaleukin monotherapy among patients with advanced mucosal or cutaneous melanoma. Additionally, a less frequent IV nemvaleukin dosing schedule is being evaluated in patients with advanced solid tumors in the ARTISTRY-3 study. Methods: ARTISTRY-6 (NCT04830124) is an ongoing phase 2, global, multicenter, open-label study that is currently enrolling. Eligible patients will have had prior anti–PD-(L)1 therapy with or without anti–CTLA-4 therapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate hematologic reserve and hepatic and renal function. In Cohort 1, patients with advanced cutaneous melanoma will receive nemvaleukin at the SC RP2D of 3 mg every 7 days. In Cohort 2, patients with advanced mucosal melanoma will receive nemvaleukin at the IV RP2D of 6 µg/kg on days 1-5 of a 21-day cycle. In Cohort 3 (added as a protocol amendment), patients with advanced cutaneous melanoma will receive IV nemvaleukin in 1 of 2 less frequent dosing schedules of 1 or 2 doses per cycle. The dosing schedules for Cohort 3 will be determined when a less frequent IV RP2D has been established in ARTISTRY-3. Patients will receive nemvaleukin until progression or intolerable toxicity. The primary objective is to evaluate the antitumor activity of nemvaleukin monotherapy defined by ORR. Additional objectives include evaluation of safety, health-related quality of life, predictive biomarkers, pharmacokinetics, immunogenicity, and pharmacodynamic effects. Clinical trial information: NCT04830124 .