Nemvaleukin Shows Promising Antitumor Activity in Advanced Solid Tumors
Key Insights
Nemvaleukin, an engineered IL-2 fusion protein, demonstrates tolerability and antitumor activity in the ARTISTRY-1 phase 1/2 trial, both as monotherapy and in combination with pembrolizumab.
The study showed a 10% overall response rate with nemvaleukin monotherapy and a 13% ORR with nemvaleukin plus pembrolizumab across heavily pretreated patients with advanced solid tumors.
Notably, a 21% ORR was observed in patients with platinum-resistant ovarian cancer (search) (PROC), a population that typically does not respond well to immunotherapy.
Mural Oncology's nemvaleukin alfa (nemvaleukin) has demonstrated promising clinical antitumor activity in the ARTISTRY-1 clinical trial, according to data published in the Journal for ImmunoTherapy of Cancer (JITC). The phase 1/2 trial evaluated nemvaleukin, both as a monotherapy and in combination with pembrolizumab, in patients with advanced solid tumors.
The ARTISTRY-1 trial, a three-part, open-label study, enrolled 286 patients with advanced solid tumors across 32 sites in seven countries from July 2016 to March 2023. The study aimed to assess the safety, tolerability, and efficacy of nemvaleukin.
Monotherapy Results
Nemvaleukin monotherapy achieved a 10% overall response rate (ORR) (7/68; 95% CI 4 to 20), with all seven responders experiencing confirmed partial responses. The responses were observed in melanoma (search) (n=4) and renal cell carcinoma (search) (n=3).
Notably, in patients with mucosal melanoma (search), the ORR was 33.3%, with two partial responses (one confirmed, one unconfirmed) out of six evaluable patients. All responders had previously progressed on CPI therapy.
Combination Therapy Results
The combination of nemvaleukin and pembrolizumab resulted in a 13% ORR (19/144; 95% CI 8 to 20), including five confirmed complete responses and 14 confirmed partial responses. Six responses occurred in PD-(L)1 inhibitor-approved tumor types, and five in PD-(L)1 inhibitor-unapproved tumor types.
In patients with platinum-resistant ovarian cancer (search) (PROC), the combination therapy showed a 21% ORR. Three confirmed responses (two complete, one partial) were observed in 14 evaluable patients. An additional unconfirmed partial response was also reported. Ulka Vaishampayan, MD, Professor at the University of Michigan, noted the significance of these results, stating that PROC does not usually respond to immunotherapy.
Safety and Tolerability
Nemvaleukin was generally well-tolerated, with a manageable safety profile. The treatment was administered in an outpatient setting, and the rate of discontinuation due to adverse events was low (4%). The most common grade 3-4 treatment-related adverse events (TREAs) were neutropenia and anemia.
Ongoing Trials
The ARTISTRY-1 trial serves as the foundation for Mural Oncology's two ongoing potentially registrational trials. Data readouts are expected in late Q1/early Q2 2025 for platinum-resistant ovarian cancer (search) (PROC) and Q2 2025 for mucosal melanoma (search).
About Nemvaleukin
Nemvaleukin alfa is an engineered fusion protein designed to enhance the antitumor effects of the IL-2 pathway while reducing the toxicities associated with aldesleukin. It selectively binds to the intermediate-affinity IL-2 receptor (search) (IL-2R), leading to preferential expansion of antitumor CD8+ T cells and natural killer cells, with minimal expansion of immunosuppressive regulatory T cells.