FDA Grants Fast Track Designation to Nemvaleukin Alfa Plus Pembrolizumab for Platinum-Resistant Ovarian Cancer

The combination of the interleukin-2 immunotherapy agent nemvaleukin alfa (previously, ALKS 4230) and pembrolizumab (Keytruda) was granted fast track designation by the FDA for the treatment of patient with platinum-resistant ovarian cancer, according to a press release from developer Alkermes plc.¹

The combination is currently under review as part of the phase 3 ARTISTRY-7 trial (NCT05092360), which will compare the use of nemvaleukin alfa plus pembrolizumab with investigator’s choice of chemotherapy in those with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. The designation is intended to facilitate the development of the combination and accelerate review.

Nemvaleukin alfa is also being examined as part of the phase 1/2 ARTISTRY-1 trial (NCT02799095) alone or in combination with pembrolizumab in patients with solid tumors.² Preliminary findings from the trial indicated that within a population of 14 patients with platinum-resistant ovarian cancer, 1 patient achieved a complete response, 3 achieved partial responses (PRs), and 6 had stable disease.

“This fast track designation in platinum-resistant ovarian cancer highlights the potential clinical utility of nemvaleukin in combination with pembrolizumab in this difficult-to-treat disease for which there is no approved immunotherapy and there remains significant need for new treatment options,” Craig Hopkinson, MD, chief medical officer and executive vice president of research & development at Alkermes, said in a press release. “We are excited to initiate our planned ARTISTRY-7 phase 3 trial in platinum-resistant ovarian cancer, as we advance nemvaleukin toward potential registration and seek to help patients living with this disease.”

The multicenter, randomized ARTISTRY-7 trial had an estimated enrollment of 376 patients who were randomized 3:1:1:3 to 1 to receive 1 of several regimens: nemvaleukin alfa and pembrolizumab, pembrolizumab alone, nemvaleukin alfa alone, or investigator’s choice of chemotherapy.

Patients received 6 µg/kg of intravenous nemvaleukin alfa per day on days 1 through 5 of each 21-day cycle and/or 200 mg of intravenous pembrolizumab on day 1 of each cycle. The control arm administered either 40 mg/m2 of intravenous pegylated liposomal doxorubicin on day 1 of every 28-day cycle; 4 mg/m2 of topotecan on days 1, 8, and 15 of every 28-day cycle or 1.25 mg/m2 on days 1 through 5 of 21-day cycles; or 1000 mg/m2 of gemcitabine on days 1 and 8 of every 21-day cycle.

The study’s primary end point was progression-free survival by investigators assessment, with key secondary end points including objective response rate, overall survival, disease control rate, duration of response, and time to response.

Aside from being examined in the ARTISTRY-1 trial (NCT02799095), nemvaleukin alpha is also being assessed in the dose-escalation, cohort-expansion phase 1/2 ARTISTRY-2 trial (NCT03861793) in combination with pembrolizumab in advanced or metastatic solid tumors. An update on both trials was presented at the 2021 American Society of Clinical Oncology Annual Meeting.

Updated data from the ARTISTRY-1 trial indicated that, in a population of patients with melanoma, single-agent nemvaleukin alpha yielded 2 PRs in patients with metastatic mucosal melanoma, 2 PRs in patients with cutaneous melanoma, and 21 patients with stable disease. As of the data cut off, 24 of 30 evaluable patients were continuing on the study. In patients with renal cell carcinoma (n = 20), 2 patients achieved a PR and 10 experienced stable disease.

Findings from the ARTISTRY-2 trial revealed that nemvaleukin selectively increased levels of CD8-positive T cells and natural killer cells, and yielded low-level transient, non–dose-dependent Treg expansion. Among the patients who were treated with the experimental agent (n = 57) during the dose-escalation portion of the trial, 17 were reported to achieve stable disease.

References

1. Alkermes Receives FDA Fast Track Designation for Nemvaleukin Alfa in Combination With Pembrolizumab for the Treatment of Platinum-Resistant Ovarian Cancer. News release. Alkermes plc. October 25, 2021. Accessed October 25, 2021. https://bit.ly/3vFRH0K
2. Nemvaleukin alfa: ARTISTRY-1 and ARTISTRY-2 clinical study Update. Presented at 2021 American Society of Clinical Oncology Annual Meeting; June 4-8, 2021; Virtual. https://bit.ly/3vMbfAz