Nemvaleukin Alfa Plus Pembrolizumab Demonstrates Promising Responses, Disease Control in Platinum-Resistant Ovarian Cancer

Treatment with nemvaleukin alfa (ALKS 4230) plus pembrolizumab (Keytruda) yielded tumor responses in patients with pretreated platinum-resistant ovarian cancer, according to data from the phase 1/2 ARTISTRY-1 trial (NCT02799095) that were presented at The Society of Gynecologic Oncology (SGO) 2022 Annual Meeting on Women’s Cancer.¹

The ARTISTRY-1 trial assessed the use of nemvaleukin alfa both as a monotherapy and in combination with pembrolizumab for patients with multiple solid tumors. In a cohort of patients with platinum-resistant ovarian cancer (n = 15), intravenous nemvaleukin alfa at 3 µg/kg plus pembrolizumab induced a notable expansion of CD8-positive T cells and natural killer cells with minimal impact on regulatory T cells. Five patients derived clinically meaningful benefit following treatment with the combination, of whom 4 had been on treatment for over a year. The overall response rate (ORR) was 28.6% and the disease control rate was 71.4% with the 3 µg/kg dose of nemvaleukin alfa plus pembrolizumab.

With regard to best change from baseline target lesion, Ira Winer, MD, PhD, FACOG, a gynecologic oncologist at the Karmanos Cancer Center and an associate professor of the Division of Gynecologic Oncology at Wayne State University, said, “there are 3 patients who still have treatment ongoing. One of the patients achieved a 100% reduction in tumor volume.”

“Nemvaleukin is a novel engineered cytokine that is based on an IL-2 backbone,” according to Winer. “It specifically [and] preferentially activates CD8[-positive] T cells, as well as natural killer T cells with minimal expansion of regulatory T cells. It is designed to harness the validated IL-2 tumor pathway while mitigating associated toxicities.”

In the single-agent, dose-escalation cohort, nemvaleukin alfa was administered intravenously from doses of 0.1 µg/kg to 10 µg/kg. The goals of the combination cohort, which included 162 patients with solid malignancies, was to characterize the safety profile of the combination and determine antitumor activity via ORR. Patients in the ovarian cancer cohort received 3 µg/kg of nemvaleukin alfa on days 1 to 5 plus 200 mg of pembrolizumab on day 1 every 3 weeks on a 21-day cycle. The cohort included a total of 16 patients.

Patients had a median age of 63 years (range, 48-83) and most were White (73%) with an ECOG performance status of 1 (73%). According to Winer, 80% of patients had high-grade serous ovarian carcinoma.

Winer went on to describe 2 patients with ovarian cancer who achieved a complete response (CR) following treatment with the combination. The first was a 48-year-old patient who had received 5 prior lines of therapy. The first confirmed CR was reported in cycle 10 with a maximum reduction in target lesions of 70%. As of February 2021, the patient had completed 2 years of treatment with pembrolizumab and is continuing treatment with single-agent nemvaleukin; the patient has an ongoing CR.

The second responder who was 83 years old at diagnosis and pretreated with 2 previous lines of therapy achieved a partial response in cycle 4 with a maximum tumor reduction of 55%. A CR was achieved during cycle 24 and the patient remains on treatment.

In terms of safety, the most common grade 3/4 adverse effects (AEs) associated with nemvaleukin alfa in the entire trial population (N = 162) were anemia (9.9%), neutropenia (9.3%), and decreased neutrophil count (9.3%). An AE related to treatment with nemvaleukin alfa led to death in 1 patient with heavily pretreated pancreatic cancer. A total of 96.3% of patients experienced any grade of AE and 40.7% experienced serious AEs. Grade 1/2 AEs related to treatment with nemvaleukin alfa occurred in 88.9% of patients and grade 3/4 AEs occurred in 46.9%. Additionally, 9.9% had AEs leading to discontinuation, 3.7% of which were related to treatment with nemvaleukin alfa.

In October 2021, the FDA granted fast track designation to nemvaleukin alfa plus pembrolizumab in patients with platinum-resistant ovarian cancer based on findings from the phase 3 ARTISTRY-7 trial (NCT05092360), which is assessing the combination in patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.²

Reference

1. Winer I. Clinical outcomes of ovarian cancer patients treated with the novel engineered cytokine nemvaleukin alfa in combination with the PD-1 inhibitor pembrolizumab: recent data from ARTISTRY-1. Poster presented at: 2022 SGO Annual Meeting on Women’s Cancer; March 18-21, 2022; Phoenix, Arizona. Accessed March 19, 2022.
2. 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 March 19, 2022. https://bit.ly/3vFRH0K