Nemvaleukin Lands FDA Fast Track Designation for Platinum-Resistant Ovarian Cancer

Fast track designation has been granted by the FDA to the investigational engineer interleukin-2 (IL-2) variant immunotherapy, nemvaleukin alfa (previously ALKS 4230), for use in combination with pembrolizumab (Keytruda) as treatment for patients with platinum-resistant ovarian cancer, according to a press release by Alkemes plc.¹

Nemvaleukin was designed to increase tumor-killing immune cells and limiting the activation of immunosuppressive cells to promote anti-tumor activity. The agent will be investigated in the phase 3 ARTISTRY-7 clinical trial (NCT05092360).

"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," said Craig Hopkinson, MD, chief medical officer and executive vice president of Research & Development at Alkermes. "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."

In the multicenter, open-label, randomized study, approximately 376 patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer will be enrolled and assigned 3:1:1:3 to receive ether nemvaleukin 6 µg/kg/day in combination with pembrolizumab 200 mg in arm 1, pembrolizumab alone in arm 2, nemvaleukin alone in arm 3, or investigator’s choice of chemotherapy in arm 4.²

In the experimental arms, nemvaleukin will be administered on days 1 through 5 of 21-day cycles by (IV) infusion. Pembrolizumab is administered on day 1 of 21-day cycles, also by IV infusion. In the control arm, chemotherapy options include pegylated liposomal doxorubicin 40 mg/m² administered on day 1 of 28-day cycles, paclitaxel 80 mg/m² given on days 1, 8, 15, and 22 of 28-day cycles, topotecan 4 mg/m² administered on days 1, 8, and 15 of 28-day cycles, or gemcitabine 1000 mg/m² given in days 1 and 2 of 21-days cycles. All chemotherapy is administered by IV infusion in the study.

ARTISTRY-7 is primarily investigating progression-free survival with nemvaleukin in combination with pembrolizumab, nemvaleukin monotherapy, and pembrolizumab monotherapy compared with chemotherapy in patients with platinum-resistant ovarian cancer. The secondary end points being explored in the study included objective response rate, overall survival rate, disease control rate, duration of response, time to response, Cancer antigen-125 response, and the incidence of treatment-emergent adverse events.

Patients who are eligible for inclusion in the study include those aged 18 years of age or older with histologically confirmed disease that is platinum-resistant or refractory and who have received at least 1 prior line of systemic anticancer therapy in the platinum-sensitive setting. Patients cannot have received more than 5 prior lines of therapy and must also have measurable disease per RECIST v1.1 and be willing to undergo tumor biopsy.

The study excludes individuals with primary platinum-refractory disease or primary platinum resistance or disease progression less than 3 months after frontline therapy is completed. Patients with histologically confirmed epithelial ovarian cancer with mucinous or carcinosarcoma subtype are ineligible for the study, as are those with a nonepithelial tumor. Tumor with low malignant potential, need fluid drainage of 500 mL or more with in 6 weeks of first dosing in the study, are previously treated with an IL-2 agent, or have had prior exposure to an anti-PD-1/PD-L1 therapy.

Previously, nemvaleukin was granted fast track and orphan drug designations from the FDA for the treatment of patients with mucosal melanoma. With a fast track designation for platinum-resistant ovarian cancer, development of the agent in this disease state will be expedited to potentially fill an unmet medical need.¹

_Reference:

_{1. Alkermes receives FDA fast track designation for nemvaleukin alfa in combination with pembrolizumab for the treatment of platinum-resistant ovarian cancer. News release. October 25, 2021. Accessed October 25, 2021. https://bit.ly/3ma7Acz}

_{2. Phase 3 study of nemvaleukin alfa in combination with pembrolizumab (ARTISTRY-7). Clinicaltrials.gov. Accessed October 25, 2021. https://bit.ly/3mdQmek}