Nemvaleukin Shows Durable Antitumor Activity in Melanoma, RCC

Nemvaleukin alfa (ALKS 4230) demonstrated durable antitumor activity as a monotherapy in patients with advanced melanoma or renal cell carcinoma (RCC) whose disease had progressed on prior immune checkpoint inhibitor (ICI) therapy, according to results from the ARTISTRY-1 trial (NCT02799095).¹

This analysis focuses on part B of the phase 1/2 first-in-human study, which evaluated intravenous nemvaleukin monotherapy at the recommended phase 2 dose (RP2D) in 74 heavily pretreated patients (melanoma, n=47; RCC, n=27). The study assessed antitumor activity, safety, pharmacokinetics, and pharmacodynamics.

Investigators reported an overall response rate (ORR) in melanoma and RCC of 9% (95% CI, 2%-21%) and 14% (95% CI, 3%-35%), respectively. Both cohorts had a disease control rate of 50% (95% CI, 35%-65%, and 95% CI, 28%-72%, respectively). Stable disease of 6 months or greater was observed in 3 patients with melanoma (7%) and 2 patients with RCC (9%).

Median progression-free survival (PFS) in the melanoma and RCC cohorts was 16.4 weeks (95% CI, 10.6-17.1) and 12.4 weeks (95% CI, 4.4-22.6), respectively. A maximum tumor size reduction of at least 30% was observed in 13% of patients with melanoma and 17% of patients with RCC.

Melanoma Cohort

In the melanoma cohort, 2 patients with cutaneous melanoma and 1 with acral melanoma had stable disease for more than 6 months. One patient with cutaneous melanoma had an ongoing response for at least 57 weeks, and another with mucosal melanoma had an ongoing response for at least 164 weeks at the time of data cut-off.

In this cohort, the PFS rates for 6 months and 1 year were 14% and 11%, respectively. All 4 confirmed responses in the melanoma cohort were partial responses; 3 of 30 (10%) were in patients with cutaneous melanoma, and 1 of 6 (17%) was in those with mucosal melanoma.

RCC Cohort

Among patients with RCC, all confirmed responders had a partial response and had been treated previously with an ICI. Twelve (55%) patients had stable disease, and 2 patients (9%) had stable disease for more than 6 months.

In the RCC cohort, 6-month and 1-year PFS rates were 19% and 10%, respectively. The median PFS was 12.4 weeks (range, 4.4–22.6), and the longest duration of response was 94 weeks.

Safety

Patients in both the melanoma and RCC cohorts received a median of 6 treatment cycles. The median duration of exposure to nemvaleukin monotherapy in both cohorts was 14.7 weeks.

In the melanoma and RCC cohorts, 45 (96%) and 27 (100%) patients, respectively, experienced at least 1 nemvaleukin-related treatment-emergent adverse event (TRAE), and 36 (77%) and 20 (74%) patients experienced at least 1 grade 3 or 4 TRAE. The most common TRAEs (≥25%) of any grade in the melanoma cohort included fever (n = 32; 68%), nausea (n = 22; 47%), and neutropenia (n = 22; 47%).

In the RCC cohort, the most common TRAEs (≥25%) of any grade included fever (n=16; 59%), chills (n = 14; 52%), and neutropenia (n = 11; 41%).

The most common grade 3 or 4 TRAE in the melanoma cohort was neutropenia (57% and 33%, respectively).

Nemvaleukin-related serious AEs were reported in 7 (15%) patients in the melanoma cohort and 8 (30%) patients in the RCC cohort. Five (7%) patients in the melanoma cohort and 4 (15%) in the RCC cohort experienced an infusion-related reaction (IRR). One (2%) patient in the melanoma cohort reported cytokine release syndrome (CRS). No CRS/IRR events of grade 3 or higher were observed in any cohort. There were no reported treatment-emergent AEs of capillary leak syndrome and febrile neutropenia in Part B.

In the melanoma cohort, dose interruptions and dose reductions due to TRAEs were reported in 40% (n=19) and 11% (n=5) of patients, respectively. In the RCC cohort, dose interruptions and dose reductions due to TRAEs were reported in 44% (n=12) and 4% (n=1) patients, respectively.

Calvo et al noted a number of study limitations. First, the phase 1/2 design and small sample sizes might have introduced bias; in addition, the lack of a comparator arm could also have contributed to bias.

“Overall, nemvaleukin demonstrated preliminary antitumor activity in patients with advanced melanoma and RCC, along with a manageable safety profile, and selective activation of the proinflammatory immune pathways, supporting its potential as an active and tolerable cytokine therapy,” the authors wrote. They recommended that future research focus on identifying optimal patient subsets and combination strategies to maximize the therapeutic benefit.

REFERENCE:

Calvo E, Boni V, Dumas O, et al. Nemvaleukin alfa monotherapy in patients with advanced melanoma and renal cell carcinoma: results from the phase 1/2 non-randomized ARTISTRY-1 trial. J Immunother Cancer. 2025;13(8):e010777. doi:10.1136/jitc-2024-010777