Abstract
TPS5612 Background: ARTISTRY-7 will evaluate the novel engineered cytokine nemvaleukin alfa (nemvaleukin, ALKS 4230) in patients (pts) with gynecologic cancers. Ovarian cancer (OC) is the 8th most common cause of cancer mortality in women. OC is an area of high unmet need, as many pts become resistant/refractory to frontline platinum-based chemotherapy. In the platinum-resistant setting, standard of care chemotherapy and anti-PD-1 therapy in clinical trials have modest response rates ranging from ~6% to 20% and ~7% to 12%, respectively. Nemvaleukin was designed to selectively bind to the intermediate-affinity interleukin-2 (IL-2) receptor, preferentially activating antitumor CD8 + T and natural killer cells with minimal regulatory T cell expansion. This selectivity may provide enhanced tumor killing and improved safety/tolerability vs high-dose IL-2. In clinical studies, nemvaleukin, as monotherapy and in combination with pembrolizumab, has shown clinical benefit in multiple tumor types, including OC. In ARTISTRY-1, in 14 evaluable patients with OC, 4 responses were observed with nemvaleukin + pembrolizumab, including 2 complete responses and 2 partial responses (ORR 28.6%; DCR 71.4%; median DOR 53.4 wks). Nemvaleukin monotherapy activity was also observed (6 melanoma and 4 renal cell carcinoma responses). Methods: ARTISTRY-7 (NCT05092360) is an ongoing phase 3, multicenter, randomized study of nemvaleukin and/or pembrolizumab vs chemotherapy. Eligible pts are women (≥18 y) with histologically confirmed epithelial OC (high-grade serous, endometrioid, clear cell), fallopian tube cancer, or primary peritoneal cancer. Pts must have had ≥1 prior line of systemic therapy (platinum-sensitive setting), ≤5 prior lines (platinum-resistant setting), and prior bevacizumab, with radiographic progression on most recent therapy. Pts 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 pts will be randomized (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 other). Pts will continue treatment until disease progression or intolerable toxicity (maximum 35 pembrolizumab cycles; nemvaleukin can be continued). The primary endpoint is investigator-assessed PFS (RECIST v1.1) in the nemvaleukin + pembrolizumab vs chemotherapy arms. Secondary/exploratory endpoints include overall survival, other antitumor measures, safety, health-related quality of life, and PK/PD effects. Clinical trial information: NCT05092360 .