On November 20, 2024 Mural Oncology plc (Nasdaq: MURA), a clinical-stage immuno-oncology company developing novel, investigational engineered therapies targeting cytokine pathways designed to address areas of unmet need for patients with a variety of cancers, reported the publication of previously reported clinical data demonstrating tolerability and antitumor activity from ARTISTRY-1, a phase 1/2 trial of the company’s lead candidate, nemvaleukin alfa (nemvaleukin) (Press release, Mural Oncology, NOV 20, 2024, View Source [SID1234648519]). The paper, titled "Nemvaleukin alfa as monotherapy and in combination with pembrolizumab in advanced solid tumors: the phase 1/2, non-randomized ARTISTRY-1 trial," was published in the Journal for ImmunoTherapy of Cancer (JITC).

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"While immunotherapies have marked a paradigm shift in the treatment of some types of cancers, many patients still face challenges, including lack of response, tolerability issues, or resistance to therapy, and there remains a great deal of unmet clinical need. In the ARTISTRY-1 study, notable antitumor activity of nemvaleukin was observed in both monotherapy and combination therapy. What was most striking were the durable and complete responses in platinum-resistant ovarian cancer, which does not usually respond to immunotherapy. These clinical data provide a solid foundation for Mural’s ongoing late-stage trials," said Ulka Vaishampayan, MD, Professor, Internal Medicine, Division of Hematology/Oncology at the University of Michigan and the paper’s lead author.

Nemvaleukin is a novel, engineered fusion protein designed to leverage the antitumor effects of the IL-2 pathway while mitigating aldesleukin’s toxicity. ARTISTRY-1 was a three-part, open-label, phase 1/2 study evaluating the safety, tolerability, and efficacy of both nemvaleukin monotherapy and combination therapy with pembrolizumab. The study was conducted at 32 sites in seven countries, with 286 patients with advanced solid tumors enrolled and treated from July 2016 to March 2023.

ARTISTRY-1 is the foundation of Mural’s two ongoing potentially registrational trials, with data readouts expected in late Q1/early Q2 2025 for platinum-resistant ovarian cancer (PROC) and Q2 2025 for mucosal melanoma.

Key Findings:

As previously reported, nemvaleukin was generally well tolerated and demonstrated promising antitumor activity alone and in combination with pembrolizumab across heavily pretreated patients with advanced solid tumors. Robust expansion of CD8+ T cells and natural killer (NK) cells, with minimal expansion of regulatory T (Treg) cells were observed following treatment, thus supporting the design hypothesis of nemvaleukin.

Monotherapy:

10% overall response rate (ORR) with nemvaleukin monotherapy (7/68; 95% CI 4 to 20), with all seven confirmed partial responses (melanoma, n=4; renal cell carcinoma, n=3).
33.3% ORR in patients with mucosal melanoma, with two partial responses (one confirmed, one unconfirmed) in six evaluable patients. All responders had been on prior CPI therapy and progressed.
Combination therapy:

13% ORR with nemvaleukin and pembrolizumab (19/144; 95% CI 8 to 20), with five confirmed complete responses and 14 confirmed partial responses. Six responses were in PD-(L)1 inhibitor-approved and five in PD-(L)1 inhibitor-unapproved tumor types.
21% ORR in patients with PROC: Notably, there were three confirmed responses (two complete, one partial) in 14 evaluable patients with PROC, which does not normally respond to immunotherapy and for which there are no approved immunotherapies. Additionally, there was one unconfirmed partial response.
Durable, stable disease for greater than 6 months was observed in patients with cervical cancer, bladder cancer, non-small-cell lung cancer, PROC, and endometrial cancer.
Safety and Tolerability:

Nemvaleukin was administered in an outpatient setting throughout treatment and had a manageable safety profile, with a low rate (4%) of discontinuation due to adverse events.
Most common grade 3-4 treatment-related adverse events (TREAs) were neutropenia and anemia.