Nemvaleukin Alfa Shows Durable Antitumor Activity in Advanced Melanoma and Renal Cell Carcinoma
Key Insights
Nemvaleukin alfa monotherapy demonstrated objective response rates of 9% in melanoma (search) and 14% in renal cell carcinoma (search) patients whose disease progressed on prior immune checkpoint inhibitor therapy.
Both cancer cohorts achieved a 50% disease control rate, with some patients maintaining stable disease for more than 6 months in the phase 1/2 ARTISTRY-1 trial.
The treatment showed a manageable safety profile with neutropenia (search) as the most common grade 3/4 adverse event, affecting 57% of melanoma (search) and 33% of RCC (search) patients.
Nemvaleukin alfa (ALKS 4230) demonstrated durable antitumor activity as a monotherapy in patients with advanced melanoma (search) or renal cell carcinoma (search) (RCC (search)) whose disease had progressed on prior immune checkpoint inhibitor (ICI) therapy, according to results from the ARTISTRY-1 trial published in the Journal for Immunotherapy of Cancer.
The 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 in 74 heavily pretreated patients (melanoma (search), n=47; RCC (search), n=27) from July 2016 to March 2023.
Clinical Efficacy Results
Investigators reported an overall response rate (ORR) in melanoma (search) and RCC (search) of 9% (95% CI, 2%–21%) and 14% (95% CI, 3%–35%), respectively. Both cohorts achieved 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 (search) and RCC (search) 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 Outcomes
In the melanoma (search) cohort, all 4 confirmed responses were partial responses; 3 of 30 (10%) were in patients with cutaneous melanoma (search), and 1 of 6 (17%) was in mucosal melanoma (search). 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.
The PFS rates for 6 months and 1 year were 14% and 11%, respectively. Two patients with cutaneous melanoma (search) and 1 with acral melanoma (search) had stable disease for more than 6 months.
RCC Cohort Outcomes
Among patients with RCC (search), 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 (search) cohort, 6-month and 1-year PFS rates were 19% and 10%, respectively. The longest duration of response was 94 weeks.
Patient Demographics and Treatment History
The median age was 66 years (range, 37-82) for patients in the melanoma (search) cohort and 69 years (range, 39-77) for those in the RCC (search) cohort. Males comprised 53% of the melanoma cohort and 89% of the RCC cohort. Most patients were White (melanoma, 89%; RCC, 93%).
Patients were heavily pretreated, with a median of 3 prior lines of therapy (range, 1-8) in the melanoma (search) cohort and 2 (range, 1-8) in the RCC (search) cohort. Prior ICI exposure was common, with anti–PD-1 (search) therapy received by 96% of patients with melanoma and 56% of patients with RCC.
Safety Profile
Patients in both melanoma (search) and RCC (search) cohorts received a median of 6 treatment cycles, with a median duration of exposure to nemvaleukin monotherapy of 14.7 weeks in both cohorts.
Nearly all patients experienced at least one nemvaleukin alfa–related treatment-emergent adverse event (TRAE), with incidences of 96% in the melanoma (search) cohort and 100% in the RCC (search) cohort. Grade 3 or 4 TRAEs occurred in 77% and 74% of patients, respectively.
The most common TRAEs (≥25%) of any grade in the melanoma (search) cohort included fever (68%), nausea (47%), and neutropenia (search) (47%). In the RCC (search) cohort, the most common TRAEs included fever (59%), chills (52%), and neutropenia (41%).
Neutropenia (search) was the most common grade 3/4 TRAE in the melanoma (search) cohort (57%) and RCC (search) cohort (33%). Nemvaleukin-related serious adverse events (SAEs) were reported in 7 (15%) patients in the melanoma cohort and in 8 (30%) patients in the RCC cohort.
Five (7%) patients in the melanoma (search) cohort and 4 (15%) in the RCC (search) cohort experienced an infusion-related reaction (IRR). One (2%) patient in the melanoma cohort reported cytokine release syndrome (search) (CRS). No CRS/IRR events of grade ≥3 were observed in any cohort. There were no reported adverse events of capillary leak syndrome and febrile neutropenia (search).
Study Design and Limitations
The phase 1/2 ARTISTRY-1 trial was a global, multicenter, open-label study conducted across 32 sites in 7 countries. In part B, nemvaleukin alfa was administered at the recommended phase 2 dose of 6 μg/kg once daily on days 1-5 of each cycle.
The authors noted several study limitations, including the phase 1/2 design and small sample sizes that might introduce bias, and the lack of a comparator arm that could also contribute bias.
"Overall, nemvaleukin demonstrated preliminary antitumor activity in patients with advanced melanoma (search) and RCC (search), 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 should focus on identifying optimal patient subsets and combination strategies to maximize the therapeutic benefit.