744 Assessment of safety and immunologic activity of nemvaleukin alfa in patients with advanced solid tumors treated with less frequent intravenous dosing (ARTISTRY-3)

• Published in: Journal for immunotherapy of cancer 2023-11, Vol.11 (Suppl 1), p.A839-A840
• Main Authors: Piha-Paul, Sarina A, Call, Justin A, Spira, Alexander I, Manzano, Aránzazu, Calvo, Emiliano, de Miguel, Maria J, Asha, Shwetha, Du, Yangchun, DiLea, Clifford, Rege, Bhaskar, Dalal, Rita, Panchabhai, Sonali, Lakhani, Nehal J
• Format: Article
• Language: English
• Subjects: Cancer; Cytokines; Immunotherapy; Pharmacodynamics; Pharmacology; Regular and Young Investigator Award Abstracts; Tumors
• ISSN: 2051-1426
• DOI: 10.1136/jitc-2023-SITC2023.0744

BackgroundNemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel engineered cytokine designed to selectively bind the intermediate-affinity interleukin-2 receptor, preferentially expanding antitumor CD8+ T and natural killer (NK) cells with minimal effect on immunosuppressive regulatory T cells (Tregs).1 In ARTISTRY-1, intravenous (IV) nemvaleukin on days 1–5 (QD×5) in 21-day cycles showed antitumor activity across multiple tumor types as monotherapy at the recommended phase 2 dose of 6 μg/kg/day and in combination with pembrolizumab at doses of 3 and 6 μg/kg/day.2 Expansion of circulating CD8+ T and NK cells was observed, with minimal effect on Tregs.2 Pharmacodynamic data from ARTISTRY-1 were used in quantitative systems pharmacology modeling studies to predict less-frequent IV dosing regimens that mimic expansion of CD8+ T and NK cells observed with 3 μg/kg/day and 6 μg/kg/day QD×5.3 We report preliminary results from ARTISTRY-3, an ongoing phase 1/2, open-label study evaluating less-frequent IV nemvaleukin dosing in advanced solid tumors.MethodsEligible patients with select solid tumors must have exhausted standard-of-care therapies. Escalating doses of nemvaleukin (10–40 μg/kg/day) were evaluated across 3 schedules in 3-week cycles (Q3W)—day 1 (D1), days 1 and 8 (D1+D8), and days 1 and 4 (D1+D4)—allowing a maximum sample size of 30 patients per schedule. The primary endpoint was incidence of DLTs from the first dose through the end of the DLT observation period. Secondary endpoints included objective response, pharmacokinetics, and severity of adverse events (AEs). Dose-escalation decisions were based on predefined safety parameters of dose-limiting toxicity (DLT) criteria evaluated during cycle 1. Pharmacodynamic assessments included absolute counts of CD8+ T, NK, and Treg cells (cells/μL) by flow cytometry at baseline and in the first 2 cycles.ResultsAs of June 1, 2023, no DLTs have been observed. Preliminary data indicate expansion of NK and CD8+ T cells at all schedules, with slightly better expansion at D1+D8 and D1+D4 Q3W schedules (figure 1). Minimal to no expansion of Tregs has been observed. The most frequent treatment-related AEs (>20%) include cytokine release syndrome and nausea; most events were grade 1–2 (Safety cutoff: April 21, 2023). There have been no grade ≥3 treatment-related AEs. Maximum serum concentration (Cmax) and exposure (AUC) increased with escalating doses (table 1).ConclusionsThis preliminary analysis demonstrates immunolog