{
  "abstract": "Background Pegenzileukin (SAR444245), a pegylated non-alpha recombinant human interleukin (IL)-2 variant, avoids engagement of the IL-2 receptor α subunit (IL-2Rα) chain and associated toxicities, while retaining engagement of IL-2Rβγ, for activation of effector T cell and natural killer (NK) cell. The first-in-human study of pegenzileukin with pembrolizumab showed initial efficacy and tolerable safety in advanced and metastatic solid tumors. In this study, we evaluate pegenzileukin with cemiplimab for advanced or metastatic melanoma (MM) and cutaneous squamous cell carcinoma (CSCC).Methods This phase 1/2, open-label, multicenter study evaluated drug combinations in patients with MM (Cohort A) and CSCC (Cohort B). Pegenzileukin was given at two dose levels (16 µg/kg: Cohort A1 and B1 and 24 µg/kg: Cohort A2 and B2) during dose escalation and recommended phase 2 dose (RP2D) during dose expansion, while cemiplimab was given at a dose of 350 mg; both drugs were administered every 3 weeks as a 30-minute intravenous infusion. The primary endpoint was the objective response rate (ORR); secondary endpoints included dose-limiting toxicities (DLTs), progression-free survival (PFS), safety, and exploratory biomarker endpoints.Results A total of 46 patients were enrolled. At the RP2D of pegenzileukin (16 µg/kg, n=20 in Cohort A1 and n=16 in Cohort B1), the ORR was 40% in Cohort A1 and 56.3% in Cohort B1. In Cohort A1, one patient achieved a complete response, and seven achieved a partial response (PR). In Cohort B1, nine patients achieved a PR. At the RP2D, 75.0% and 85.7% responders, respectively, in Cohort A1 and Cohort B1 had a duration of response of ≥12 months. The PFS rate at 6 months was 55.0% in Cohort A1 and 70.7% in Cohort B1. Five DLTs occurred in four patients: Cohort A had one case of ≥3 Grade thrombocytopenia and one of Grade 2 cytokine release syndrome, while Cohort B had one case of ≥3 Grade alanine transaminase/aspartate transaminase increases and one infusion-related reaction (IRR). Grade 1 or 2 IRRs were the most common adverse events. Treatment led to robust expansion of NK and CD8 T-cells, without an increase of regulatory T cells.Conclusion Pegenzileukin in combination with cemiplimab at the RP2D of 16 µg/kg showed a manageable safety profile and promising translational data supporting its mechanism of action.Trial registration number NCT04913220.",
  "authors": [
    {
      "affiliations": [
        "Medical Oncology, Bradford Hill Centro de investigación en cáncer, Santiago, Santiago Metropolitan Region, Chile",
        "Universidad Finis Terrae, Santiago, Santiago Metropolitan Region, Chile"
      ],
      "name": "Carlos Rojas"
    },
    {
      "affiliations": [
        "Service de Dermatologie, CHU Lille, Lille, France"
      ],
      "name": "Laurent Mortier"
    },
    {
      "affiliations": [
        "Macquarie Medical School, Macquarie University, Sydney, New South Wales, Australia"
      ],
      "name": "John J Park"
    },
    {
      "affiliations": [
        "Department of Oncology, Instituto Oncológico Fundación Arturo López Pérez, Santiago, Chile"
      ],
      "name": "Luis Matamala"
    },
    {
      "affiliations": [
        "Sanofi SA Recherche and Developpement, Paris, Île-de-France, France"
      ],
      "name": "Adyb Baakili"
    },
    {
      "affiliations": [
        "Sanofi, Cambridge, Massachusetts, USA"
      ],
      "name": "Saleem Rao"
    },
    {
      "affiliations": [
        "Sanofi, Cambridge, Massachusetts, USA"
      ],
      "name": "Jing Xu"
    },
    {
      "affiliations": [
        "Sanofi SA Recherche and Developpement, Paris, Île-de-France, France"
      ],
      "name": "Laurent Andrieu"
    },
    {
      "affiliations": [
        "Sanofi, Cambridge, Massachusetts, USA"
      ],
      "name": "Rui Wang"
    },
    {
      "affiliations": [
        "Sanofi, Cambridge, Massachusetts, USA"
      ],
      "name": "Hong Wang"
    },
    {
      "affiliations": [
        "Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany"
      ],
      "name": "Tobias Paehler"
    },
    {
      "affiliations": [
        "Sanofi, Cambridge, Massachusetts, USA"
      ],
      "name": "Giovanni Abbadessa"
    },
    {
      "affiliations": [
        "Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy",
        "Università degli Studi di Napoli Federico II, Naples, Campania, Italy"
      ],
      "name": "Paolo A Ascierto"
    }
  ],
  "title": "Phase 1/2 study of pegenzileukin, a pegylated recombinant non-alpha IL-2, with cemiplimab for the treatment of advanced unresectable or metastatic skin cancers",
  "uid": "5bc16690-1cc3-5f7a-8caa-ffb7bfb79171"
}