FDA Grants Fast Track Status to Nemvaleukin Alfa for Mucosal Melanoma

FDA

The FDA has granted a fast track designation to the interleukin-2 (IL-2) variant immunotherapy nemvaleukin alfa as a potential therapeutic option for patients with mucosal melanoma, according to an announcement from Alkermes plc, the drug developer.¹

The investigational, engineered fusion protein is made up of modified IL-2 and the high affinity IL-2 alpha receptor chain. Moreover, the agent was designed to selectively expand cancer-killing immune cells without activating immunosuppressive cells by preferentially binding to the intermediate-affinity IL-2 receptor complex. The selectivity of nemvaleukin is designed to leverage the antitumor effects of existing IL-2 therapy while overcoming certain limitations.

“Receiving fast track designation from the FDA for nemvaleukin for the treatment of mucosal melanoma is an important milestone for the nemvaleukin development program and underscores nemvaleukin’s potential clinical utility to address an unmet medical need in this difficult-to-treat tumor type,” Craig Hopkinson, MD, chief medical officer, and executive vice president of Research & Development at Alkermes, stated in a press release. “We are committed to advancing this important research in mucosal melanoma, a rare and aggressive form of melanoma for which there are very limited treatment options, particularly for those patients previously treated with checkpoint inhibitors.”

The phase 2 ARTISTRY-6 trial (NCT04830124) is designed to evaluate the antitumor activity, safety and tolerability of intravenous nemvaleukin in patients with mucosal melanoma. The study also includes a cohort of patients with advanced cutaneous melanoma who will receive subcutaneous nemvaleukin with intent to establish monotherapy proof-of-concept with the subcutaneous dosing.²

To be eligible for enrollment, patients need to have advanced cutaneous melanoma or acral melanoma (Cohort 1) Or, the patient must have unresectable and/or metastatic mucosal melanoma (Cohort 2).

Patients must have previously received: an anti–PD-(L)1 therapy with or without an anti–CTLA-4 therapy, and 1 or fewer other prior regimens of systemic anti-neoplastic therapy; or anti–PD-(L)1 therapy and experienced an objective response or stable disease as their best overall response to treatment.³ Notably patients whose tumors harbored BRAF mutations could or could not have previous targeted treatment.

Additionally, patients need to have measurable disease per RECIST v1.1 criteria, be willing to undergo a pretreatment tumor biopsy or provide qualifying archival tumor tissue, have an ECOG performance status of 0 to 1, and an estimated life expectancy of at least 3 months.

Patients could not have uveal melanoma, have previously received IL-2–based or IL-15–based cytokine therapy, require systemic corticosteroids, previously undergone solid organ and/or non-autologous hematopoietic stem cell or bone marrow transplant, or have known or suspected hypersensitivity to any components of nemvaleukin.

The study is planned to enroll approximately 110 patients, who will be enrolled to 1 of 2 cohorts. The first cohort will include patients with advanced mucosal melanoma who will receive nemvaleukin at a daily intravenous dose of 6 µg/kg for 5 consecutive days every 3 weeks. The second cohort will comprise patients with advanced cutaneous melanoma who will receive subcutaneous nemvaleukin at a dose of 3 mg once every 7 days.

The primary end point of the trial is overall response rate per central assessment and based on RECIST v1.1 criteria, which will be examined for patients with mucosal or cutaneous melanoma. Key secondary end points are comprised of safety and tolerability, duration of response, progression-free survival, disease control rate, and time to response based on RECIST v1.1 criteria.

Investigators will also examine health-related quality of life, as well as the pharmacokinetic and pharmacodynamic effects of both intravenous and subcutaneous administration of single-agent nemvaleukin.

“The initiation of the ARTISTRY-6 study represents a significant milestone in the nemvaleukin development program, building on the early signals of antitumor activity observed with IV nemvaleukin in melanoma,” Hopkinson stated in a prior press release. “Consistent with our strategy to study nemvaleukin in difficult-to-treat cancers with clear unmet need, we look forward to further evaluating the potential clinical utility of nemvaleukin monotherapy in mucosal melanoma, a rare and aggressive form of melanoma that has very limited treatment options.”

Previously, in March 2021, the FDA granted an orphan drug designation to nemvaleukin for the treatment of patients with mucosal melanoma.⁴

References

1. Alkermes receives FDA fast track designation for nemvaleukin alfa for the treatment of mucosal melanoma. News release. Alkermes plc. August 2, 2021. Accessed August 2, 2021. https://bit.ly/2WMtb0G
2. Alkermes initiates ARTISTRY-6 trial of nemvaleukin alfa monotherapy in patients with melanoma. News release. Alkermes plc. April 27, 2021. Accessed August 2, 2021. https://bit.ly/3xf9Ql7
3. Nemvaleukin alfa (ALKS 4230) monotherapy in patients with advanced cutaneous melanoma or advanced mucosal melanoma – ARTISTRY-6 (ARTISTRY-6). ClinicalTrials.gov. Updated June 10, 2021. Accessed August 2, 2021. https://clinicaltrials.gov/ct2/show/NCT04830124
4. Alkermes announces FDA orphan drug designation for nemvaleukin alfa for treatment of mucosal melanoma. News release. Alkermes plc. March 11, 2021. Accessed August 2, 2021. https://bit.ly/2VttPzh