Abstract 1034TiP
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, intravenous (IV) recommended phase II 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, subcutaneous (SC) RP2D of 3 mg q7d was identified demonstrating pharmacodynamic effects consistent with IV. Data support further evaluation of nemvaleukin monotherapy among patients with advanced mucosal and cutaneous melanoma.
Trial design
ARTISTRY-6 is a phase II, 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, 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 R2PD, respectively. Patients will receive nemvaleukin until progression or intolerable toxicity. The primary objective is to evaluate the antitumor activity of nemvaleukin monotherapy. Additional objectives include the evaluation of safety, health-related quality of life, predictive biomarkers, pharmacokinetics, immunogenicity, and pharmacodynamic effects.
Clinical trial identification
NCT04830124.
Editorial acknowledgement
Medical writing and editorial support was provided by Melanie J. Jardim, PhD, of Parexel International.
Legal entity responsible for the study
Alkermes, Inc.
Funding
Alkermes, Inc.
Disclosure
R.D. Carvajal: Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Castle Biosciences; Financial Interests, Personal, Advisory Role: Compugen; Financial Interests, Personal, Advisory Role: Foundation Medicine; Financial Interests, Personal, Advisory Role: Immunocore; Financial Interests, Personal, Advisory Role: I-Mab; Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Roche/Genentech; Financial Interests, Personal, Advisory Role: Pure Tech Health; Financial Interests, Personal, Advisory Role: Sanofi Genzyme; Financial Interests, Personal, Advisory Role: Sorrento Therapeutics; Financial Interests, Personal, Advisory Board: Aura Biosciences; Financial Interests, Personal, Advisory Board: Chimeron; Financial Interests, Personal, Advisory Board: Rgenix; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: Astellis; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: Bellicum; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Funding: Corvus; Financial Interests, Institutional, Funding: Eli Lilly; Financial Interests, Institutional, Funding: Immunocore; Financial Interests, Institutional, Funding: Incyte; Financial Interests, Institutional, Funding: Macrogenics; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Mirati; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Plexxikon; Financial Interests, Institutional, Funding: Roche/Genentech. J.S. Weber: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board, SAB member: Cytomx; Financial Interests, Personal, Member, SAB member: Sellas; Financial Interests, Personal, Member, SAB member: Neximmune; Financial Interests, Personal, Advisory Board: Idera; Financial Interests, Personal, Advisory Board: OncoSec; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Member, SAB member: Celldex; Financial Interests, Personal, Member, SAB member: Protean; Financial Interests, Personal, Member, SAB member: Evaxion; Financial Interests, Personal, Advisory Board: Editas; Financial Interests, Personal, Member, DSMB: Ultimovacs; Financial Interests, Personal, Advisory Board: Immunocore; Financial Interests, Personal, Advisory Board, SAB Member: Biond; Financial Interests, Personal, Stocks/Shares: Neximmune; Financial Interests, Personal, Stocks/Shares: CytoMx; Financial Interests, Personal, Stocks/Shares: Biond; Financial Interests, Personal, Stocks/Shares: Celldex; Financial Interests, Personal, Royalties, Named on a patent from Moffitt Cancer Center: Iovance; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Moderna. A.Z. Dudek: Financial Interests, Personal, Advisory Role: HiberCell; Financial Interests, Personal, Member of the Board of Directors, Chief Medical Officer: Vanquish Oncology; Financial Interests, Personal, Member of the Board of Directors, Chief Medical Officer: TTC Oncology; Financial Interests, Personal, Member of the Board of Directors, Chief Medical Officer: IGF Oncology; Financial Interests, Personal, Member of the Board of Directors, Chief Medical Officer: Squarex; Financial Interests, Personal, Member of the Board of Directors: Martell Diagnostic Laboratory; Financial Interests, Personal, Stocks/Shares: Vanquish Oncology; Financial Interests, Personal, Stocks/Shares: IFG Oncology; Financial Interests, Personal, Stocks/Shares: TTC Oncology; Financial Interests, Personal, Stocks/Shares: Martell Diagnostic Laboratory; Financial Interests, Personal, Stocks/Shares: Squarex; Financial Interests, Personal, Stocks/Shares: Luminary Therapeutics; Non-Financial Interests, Personal, Principal Investigator: Hiber Cell; Financial Interests, Personal, Leadership Role: Midwest Melanoma Partnership. O. Hamid: Financial Interests, Personal, Advisory Role: Aduro; Financial Interests, Personal, Advisory Role: Akeso; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Beigene; Financial Interests, Personal, Invited Speaker, Consultant: BMS; Financial Interests, Personal, Advisory Role: Roche Genentech; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: Immunocore; Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Nextcure; Financial Interests, Personal, Invited Speaker, Consultant: Novartis; Financial Interests, Personal, Invited Speaker, Consultant: Pfizer; Financial Interests, Personal, Invited Speaker, Consultant: Sanofi; Financial Interests, Personal, Invited Speaker, Consultant: Regeneron; Financial Interests, Personal, Advisory Role: SeaGen; Financial Interests, Personal, Advisory Role: Tempus; Financial Interests, Personal, Advisory Role: Zelluna; Financial Interests, Personal, Principal Investigator: Arcus; Financial Interests, Personal, Principal Investigator: Aduro; Financial Interests, Personal, Principal Investigator: Akeso; Financial Interests, Personal, Principal Investigator: Amgen; Financial Interests, Personal, Principal Investigator: Bioatla; Financial Interests, Personal, Principal Investigator: BMS; Financial Interests, Personal, Principal Investigator: CytomX; Financial Interests, Personal, Principal Investigator: Exelixis; Financial Interests, Personal, Principal Investigator: Roche Genentech; Financial Interests, Personal, Principal Investigator: GSK; Financial Interests, Personal, Principal Investigator: Immunicore; Financial Interests, Personal, Principal Investigator: Idera; Financial Interests, Personal, Principal Investigator: Incyte; Financial Interests, Personal, Principal Investigator: Iovance; Financial Interests, Personal, Principal Investigator: Merck, Moderna; Financial Interests, Personal, Principal Investigator: Merck, Serono, Nextcure; Financial Interests, Personal, Principal Investigator: Novartis, Pfizer; Financial Interests, Personal, Principal Investigator: Sanofi/Regeneron; Financial Interests, Personal, Principal Investigator: SeaGen, Torque; Financial Interests, Personal, Principal Investigator: Zelluna; Financial Interests, Institutional, Research Grant: Arcus; Financial Interests, Institutional, Funding: Adura; Financial Interests, Institutional, Funding: Akeso; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: Bioatla; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Funding: CytomX; Financial Interests, Institutional, Funding: Exelixis; Financial Interests, Institutional, Funding: Roche Genentech; Financial Interests, Institutional, Funding: GSK; Financial Interests, Institutional, Funding: Immunicore; Financial Interests, Institutional, Funding: Idera; Financial Interests, Institutional, Funding: Incyte; Financial Interests, Institutional, Funding: Iovance; Financial Interests, Institutional, Funding: Merck, Moderna; Financial Interests, Institutional, Funding: Merck-Serona, Nextcure; Financial Interests, Institutional, Funding: Novartis, Pfizer; Financial Interests, Institutional, Funding: Sanofi/Regeneron; Financial Interests, Institutional, Funding: SeaGen, Torque; Financial Interests, Institutional, Funding: Zelluna. Y. Du: Financial Interests, Personal, Full or part-time Employment, Stocks: Alkermes. M. Desai: Financial Interests, Personal, Full or part-time Employment, Stocks, Patent: Alkermes. Y. Wang: Financial Interests, Personal, Full or part-time Employment, Stocks: Alkermes. L. Sun: Financial Interests, Personal, Full or part-time Employment, Stocks: Alkermes. J. Rege: Financial Interests, Personal, Full or part-time Employment, Stocks: Alkermes. M.R. Middleton: Financial Interests, Personal, Advisory Board: Alkermes; Financial Interests, Personal, Advisory Board: Kineta; Financial Interests, Personal, Advisory Board: Silicon Therapeutics; Financial Interests, Personal, Advisory Board: Immunocore; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Replimune; Financial Interests, Institutional, Funding: Alkerms; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Funding: Replimune; Financial Interests, Institutional, Funding: GSK; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: MSD; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Regeneron; Financial Interests, Institutional, Funding: Bioline; Financial Interests, Institutional, Funding: Immunocore; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Medivir; Financial Interests, Institutional, Funding: GenesisCare; Financial Interests, Institutional, Funding: GRAIL. All other authors have declared no conflicts of interest.