Nanrilkefusp alfa (nanril; SOT101) is an interleukin (IL)-15 receptor βγ superagonist that stimulates natural killer (NK) and CD8+ T cells, thereby promoting an innate and adaptive anti-tumor inflammatory microenvironment in mouse tumor models either in monotherapy or combined with an anti-programmed cell death protein 1 (PD-1) antibody. In cynomolgus monkeys, a clinical schedule was identified, which translated into the design of a phase 1/1b clinical trial, AURELIO-03 (NCT04234113). In 51 patients with advanced/metastatic solid tumors, nanril increased the proportions of CD8+ T cells and NK cells in peripheral blood and tumors. It had a favorable safety profile when administered subcutaneously on days 1, 2, 8, and 9 of each 21-day cycle as monotherapy (0.25-15 μg/kg) or combined (1.5-12 μg/kg) with the anti-PD-1 pembrolizumab (200 mg). The most frequent treatment-emergent adverse events were pyrexia, injection site reactions, and chills. Furthermore, early clinical efficacy was observed, including in immune checkpoint blockade-resistant/refractory patients.

Cytune Pharma 44300 Nantes France

Department of Lnvestigational Cancer Therapeutics MD Anderson Cancer Center Houston TX 77030 USA

Department of Medical Oncology Centre Leon Berard 69008 Lyon France

Gustave Roussy Departement d'Innovation Therapeutique et d'Essais Precoces Universite Paris Saclay 94805 Villejuif France

Institut Universitaire du Cancer de Toulouse 31100 Toulouse France

Laboratory of Immunological and Tumor Models Institute of Molecular Genetics of the Czech Academy of Sciences 142 20 Prague Czech Republic

Masaryk Memorial Cancer Institute 602 00 Brno Czech Republic

SOTIO Biotech a s 170 00 Prague Czech Republic

SOTIO Biotech a s 170 00 Prague Czech Republic; Department of Immunology 2nd Faculty of Medicine and University Hospital Motol Charles University 150 06 Prague Czech Republic

SOTIO Biotech AG 4056 Basel Switzerland

Vall d'Hebron Institute of Oncology 08035 Barcelona Spain

Yale School of Medicine New Haven CT 06510 USA

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