An overview of the phase 3 ARTISTRY-7 trial involving combination therapy with nemvaleukin alfa and pembrolizumab was presented at 2022 SGO.
The ongoing phase 3 ARTISTRY-7 trial (NCT05092360) is actively recruiting patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer to examine whether treatment with nemvaleukin alfa plus pembrolizumab (Keytruda) leads to superior outcomes vs protocol-specific investigator’s choice of chemotherapy, according to a poster presented by Thomas J. Herzog, MD, and colleagues at The Society of Gynecologic Oncology (SGO) 2022 Annual Meeting on Women’s Cancer.1
The regimen’s success will be measured with the primary end point of progression-free survival (PFS) and secondary outcomes of objective response rate, overall survival, disease control rate, duration of response, time to response, cancer antigen–125 response, and safety. Patients will be stratified according to PD-L1 status, histology, and chemotherapy. The study has a recruitment goal of 376 patients.
Rationale for the trial includes the high rate of recurrence observed in patients treated with standard frontline platinum-based chemotherapy, which may be as high as 70% at 2 years.2 The engineered cytokine nemvaleukin selectively binds with intermediate affinity for the interleukin (IL)–2 receptor, resulting in activation and expansion of CD8-positive T-cells and natural killer cells while being associated with lower toxicity than high-dose IL-2. When used in combination with pembrolizumab in the ARTISTRY-1 trial, nemvaleukin was able to induce antitumor responses in patients with platinum-resistant ovarian cancer who were pretreated with between 2 and 6 lines of prior therapy. More details from that trial are expected to be presented at the SGO 2022 Annual Meeting on Women’s Cancer.
Moreover, nemvaleukin plus pembrolizumab was granted fast tracked designation by the FDA in October 2021 for the treatment of patients with platinum-resistant ovarian cancer, which will help expediate development and review of the combination in this area considered to be an unmet medical need.
Those eligible for inclusion are women aged 18 years or older with platinum-resistant epithelial ovarian cancer. All patients must have previously received 1 or more prior lines of systemic therapy in the platinum-sensitive setting, 5 or fewer lines of therapy in the platinum-resistant space, prior bevacizumab (Avastin), and a prior PARP inhibitor for patients with BRCA mutations. Evidence of radiographic progression on or after the most recent therapy is also required. Additionally, all participants must have an ECOG performance status of 0 or 1, an estimated life expectancy of at least 3 months, and adequate hematologic reserve or hepatic and renal function.
Patients who were previously refractory or resistant to platinum therapy; received prior PD-(L)1 or IL-1, IL-15, or IL-12 therapy; have epithelial ovarian cancer with mucinous or carcinosarcoma subtype, nonepithelial tumors; or fluid drainage of at least 500 mL within 6 weeks of study drug initiation are not eligible to be treated on the trial.
Patients will be randomized in a 3:1:1:3 fashion to either intravenous pembrolizumab at 200 mg on day 1 and intravenous nemvaleukin at 6 μg/kg on days 1 through 5 of each 21-day cycle (n = 141); single-agent nemvaleukin at the same dose (n = 47); pembrolizumab monotherapy at the same dose (n = 47); or investigator’s choice of chemotherapy (n = 141). Chemotherapy options include gemcitabine at 1000 mg/m2 on days 1 and 8 of each 21-day cycle; paclitaxel at 80 mg/m2 on days 1, 8, 15 and 22 of each 28-day cycle; pegylated liposomal doxorubicin at 40 mg/m2 on day 1 of each 28-day cycle; or topotecan at 4 mg/m2 on days 1, 8, and 15 of each 28-day cycle.
Treatment with pembrolizumab will continue until disease progression or treatment intolerance for a maximum of 35 weeks for pembrolizumab; nemvaleukin treatment can continue past this timepoint.