Background Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel, engineered cytokine that selectively binds to the intermediate-affinity interleukin-2 receptor to preferentially activate antitumor CD8+ T cells and natural killer cells, with minimal expansion of immunosuppressive regulatory T cells. The first-in-human study, ARTISTRY-1, demonstrated antitumor activity with intravenous (IV) nemvaleukin (6 µg/kg on days 1–5 per 21-day cycle) monotherapy and nemvaleukin + pembrolizumab, with manageable safety in heavily pretreated adults with advanced solid tumors.1 ARTISTRY-2 (NCT03861793) is a phase 1/2 study evaluating the safety, antitumor activity, and pharmacokinetics/pharmacodynamics of subcutaneous (SC) nemvaleukin + pembrolizumab in patients with advanced solid tumors.
Methods In ARTISTRY-2, the recommended phase 2 dose (RP2D) of SC nemvaleukin was identified as 3 mg every 7 days (Q7D).2 In phase 2, SC nemvaleukin + pembrolizumab was administered in the following cohorts: non-small-cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), gastric and gastroesophageal junction cancer (G/GEJ), and ovarian cancer Cohorts 1 (OC1) and 2 (OC2). OC2 cohort included definition of platinum resistance, number of prior lines of therapy and requirement for prior treatment with bevacizumab, reflecting baseline characteristics associated with higher likelihood of clinical benefit. Investigator-assessed antitumor activity (RECIST v1.1) and safety are reported as of April 21, 2023.
Results In phase 2, 59 patients (11 NSCLC, 10 SCCHN, 13 G/GEJ, 17 OC1, 8 OC2) received SC nemvaleukin + pembrolizumab. Antitumor activity was observed, including 2 partial responses (PRs) in OC (ORR 15.4% [OC1, 2/13]) and 1 PR in NSCLC (ORR 10% [NSCLC, 1/10]); responders were checkpoint inhibitor-naive. The most frequent treatment-related adverse events (TRAEs) of any grade (>40%) included pyrexia (50.8%) and injection-site reactions (45.8%), and of grade 3/4 (>5%) were fatigue (6.8%), lymphocyte count decreased (6.8%), and lymphopenia (5.1%). A total of 7 patients (11.9%) discontinued the study due to TRAEs. There was 1 treatment-related grade 5 event of pneumonitis (NSCLC cohort). The safety profile of SC nemvaleukin + pembrolizumab was consistent with that reported for IV dosing, except for injection-site reactions.
Conclusions SC nemvaleukin 3 mg Q7D with pembrolizumab was generally well tolerated and demonstrated antitumor activity in patients with refractory solid tumors. Although antitumor activity was observed, the robustness of this activity was less than that observed with the daily ×5 IV dosing; therefore, a less frequent IV dosing schedule of nemvaleukin is being explored in ARTISTRY-3 (NCT04592653).
Acknowledgements The authors would like to thank all the patients who are participating in this study and their families. The study is sponsored by Alkermes, Inc. Medical writing and editorial support was provided by Parexel International and funded by Alkermes, Inc.
Trial Registration Clinicaltrials.gov NCT03861793
Vaishampayan U, Tomczak P, Muzaffar J, et al. Nemvaleukin alfa monotherapy and in combination with pembrolizumab in patients (pts) with advanced solid tumors: ARTISTRY-1. J Clin Oncol. 2022;40(16_suppl). Abstract #2500.
Hamid O, Liu SV, Boccia RV, et al. Selection of the recommended phase 2 dose (RP2D) for subcutaneous nemvaleukin alfa: ARTISTRY-2. J Clin Oncol. 2021;39(15_suppl). Abstract #2552.
Ethics Approval The study protocol and its amendments, patient informed consent form, and all relevant documents were approved by an institutional review board or local ethics committee. This study is being conducted according to Declaration of Helsinki and all applicable guidelines from the International Council on Harmonisation (ICH) E6 Good Clinical Practice, US Code of Federal Conduct, and state, local and federal laws. All patients are required to provide written informed consent to participate.
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