Nanrilkefusp alfa (SOT101), an IL-15 receptor βγ superagonist, as a single agent or with anti-PD-1 in patients with advanced cancers
Nanrilkefusp alfa (nanril; SOT101) is an interleukin (IL)-15 receptor βγ superagonist that stimulates natural killer (NK) and CD8<sup>+</sup> 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<sup>+</sup> 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.
Authors
- Carlos Gomez‐Roca (ORCID: https://orcid.org/0000-0002-8043-2529)
- Romana Mikyšková (ORCID: https://orcid.org/0000-0002-6857-1155)
- Radek Špíšek
- A Schoenenberger (ORCID: https://orcid.org/0009-0003-3656-2240)
- David Béchard (ORCID: https://orcid.org/0000-0003-1817-3324)
- Iphigénie Korakis (ORCID: https://orcid.org/0000-0002-2112-5932)
- Nada Podzimkova
- Kaïssa Ouali (ORCID: https://orcid.org/0000-0002-8269-3001)
- Milan Reiniš (ORCID: https://orcid.org/0000-0001-7083-2898)
- Philippe A. Cassier (ORCID: https://orcid.org/0000-0003-3857-1688)
- Vladimir Galvao (ORCID: https://orcid.org/0009-0007-8139-8215)
- Richard Sachse
- Sascha Tillmanns
- Irena Adkins
- Elena Garralda (ORCID: https://orcid.org/0000-0002-4412-7842)
- Ulrich Moebius
- Stéphane Champiat (ORCID: https://orcid.org/0000-0002-0741-2118)
- Peter Grell (ORCID: https://orcid.org/0000-0001-8241-0609)
- Patricia LoRusso (ORCID: https://orcid.org/0000-0001-7144-036X)
- Aurélien Marabelle (ORCID: https://orcid.org/0000-0002-5816-3019)
- Joachim Kiemle-Kallee
- Lenka Palová Jelínková
- Aung Naing
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- Charles University (CZ)
- Université Paris-Saclay (FR)
- Institut Gustave Roussy (FR)
- Yale University (US)
- University Hospital in Motol (CZ)
- Centre Léon Bérard (FR)
- Sotio (Czechia) (CZ)
- Masaryk Memorial Cancer Institute (CZ)
- TherapeuticsMD (United States) (US)
- Czech Academy of Sciences, Institute of Molecular Genetics (CZ)
- Vall d'Hebron Institute of Oncology (ES)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-02-01
- DOI
- https://doi.org/10.1016/j.xcrm.2025.101967
- Citations
- 4
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 4.18