Abstract
Introduction/Background ARTISTRY-7 will evaluate the novel engineered cytokine nemvaleukin alfa (nemvaleukin) in gynaecologic cancers. Nemvaleukin was designed to selectively bind to the intermediate-affinity interleukin-2 (IL-2) receptor, preferentially activating antitumour CD8+ T and NK cells with minimal regulatory T cell expansion, which may provide enhanced tumour killing and improved safety/tolerability versus high-dose IL-2. In preclinical studies, addition of a mouse nemvaleukin ortholog to anti-PD-1 treatment slowed tumour growth and increased survival in the EMT6 mouse tumour model. In ARTISTRY-1, responses were observed with nemvaleukin+pembrolizumab in 4 patients with platinum-resistant ovarian cancer (OC): 2 complete responses (1 in a patient with 5 prior lines of therapy), and 2 partial responses. Methodology ARTISTRY-7 (NCT05092360) is an ongoing phase 3, multicentre, randomised study of nemvaleukin and/or pembrolizumab versus chemotherapy that is currently enrolling. Eligible patients are women (≥18 years) with histologically confirmed epithelial ovarian (high-grade serous, endometrioid, clear cell), fallopian tube, or primary peritoneal cancer. Patients must have had ≥1 prior line of platinum-based therapy, ≤5 prior lines of systemic anticancer therapy (platinum-resistant setting), and prior bevacizumab, with radiographic progression on most recent therapy. Patients with primary platinum-refractory disease (progression on first-line platinum therapy) or primary platinum resistance (progression <3 months after first-line platinum therapy completion) are excluded. Approximately 376 patients will be randomised (3:1:1:3) to receive nemvaleukin 6 μg/kg IV (days 1–5)+pembrolizumab 200 mg IV (day 1) of each 21-day cycle, pembrolizumab or nemvaleukin monotherapy, or chemotherapy, and stratified by PD-L1 status, histologic subtype, and chemotherapy (paclitaxel vs others). Patients will continue treatment until disease progression or intolerable toxicity (maximum 35 pembrolizumab cycles; nemvaleukin can be continued). Primary endpoint: investigator-assessed progression-free survival (RECIST v1.1) with nemvaleukin+pembrolizumab vs chemotherapy. Secondary/exploratory endpoints include overall survival, other antitumor measures, safety, health-related quality of life, and pharmacokinetic/pharmacodynamic effects. Results Trial in progress Conclusion Pending data availability Disclosures This study is funded by Alkermes, Inc. Medical writing and editorial support was provided by Parexel International, and funded by Alkermes, Inc.