{
  "abstract": "Background Peltopepimut-S is a therapeutic vaccine, which induces specific expansion of both CD4+helper and CD8+cytotoxic T-cells against human papillomavirus type 16 (HPV16) E6/E7 oncoproteins.Patients and methods In a randomized phase 2 trial, we evaluated the efficacy and safety of peltopepimut-S plus cemiplimab compared with cemiplimab alone as first-line or second-line therapy in recurrent/metastatic HPV16-positive head and neck cancer. The primary efficacy endpoint was the objective response rate (ORR) by an independent review (Response Evaluation Criteria in Solid Tumors version 1.1, RECIST v1.1), while the primary safety endpoint was frequency and severity of adverse events. Secondary endpoints included progression-free survival (PFS) and overall survival (OS).Results Overall, 198 anti-programmed cell death protein-1 therapy-naïve patients with confirmed HPV16-positive recurrent/metastatic oropharyngeal cancer were randomized to receive cemiplimab plus peltopepimut-S (n=100) or placebo (n=99). The trial did not meet its primary objective (ORR, 25.3% in peltopepimut-S arm vs 22.9% in placebo arm; p=0.735). The median OS (mOS) and PFS in the placebo arm were unexpectedly longer than in the peltopepimut-S arm (26.9 vs 15.8 months) and (20.3 vs 5.5 months), respectively. In predefined exploratory analyses this was associated with an excess death rate from progressive disease in patients with pre-treatment programmed death-ligand 1 (PD-L1) combined positive score (CPS) <20. In contrast, patients with CPS ≥20 had a higher ORR of 51.7% (95% CI, 32.5% to 70.6%) vs 25.8% (95% CI, 11.9% to 44.6%) and a longer mOS in the peltopepimut-S arm (34.8 vs 28.8 months) compared with the placebo arm, respectively. If patients had received all three vaccine or placebo doses, the ORR in patients with CPS ≥20 was 70.0% (95% CI, 45.7% to 88.1%) vs 29.2% (95% CI, 12.6% to 51.1%) in the peltopepimut-S arm and placebo arms, respectively, associated with mOS not reached (after 42 months) versus 23.3 months. The addition of peltopepimut-S to cemiplimab did not increase cemiplimab’s toxicity.Conclusion Adding peltopepimut-S to cemiplimab did not improve ORR and worsened mOS in the primary analysis. Divergent outcomes were seen in patients with pretreatment PD-L1 CPS <20 (worse ORR and mOS compared with placebo) and CPS ≥20 (higher ORR and longer mOS compared with placebo) values. Future drug development is justifiable in the CPS ≥20 patient population.Trial registration number NCT03669718.",
  "authors": [
    {
      "affiliations": [
        "Head and Neck Oncology, Gustave Roussy Institute, Villejuif, Île-de-France, France"
      ],
      "name": "Caroline Even"
    },
    {
      "affiliations": [
        "Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK"
      ],
      "name": "Kevin J Harrington"
    },
    {
      "affiliations": [
        "Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, California, USA"
      ],
      "name": "Erminia Massarelli"
    },
    {
      "affiliations": [
        "Department of Otorhinolaryngology and Head and Neck Surgery, Universitatsklinikum Ulm, Ulm, Germany"
      ],
      "name": "Simon Laban"
    },
    {
      "affiliations": [
        "Centre Léon Bérard, Lyon, France"
      ],
      "name": "Jérôme Fayette"
    },
    {
      "affiliations": [
        "Institut Catala d’Oncologia, L’Hospitalet de Llobregat, Spain"
      ],
      "name": "Marc Oliva"
    },
    {
      "affiliations": [
        "TargED Biopharmaceuticals, Leiden, The Netherlands"
      ],
      "name": "Marielle Klein Hesselink"
    },
    {
      "affiliations": [
        "SVisscher-Consultancy, Gouda, The Netherlands"
      ],
      "name": "Sonja Visscher"
    },
    {
      "affiliations": [
        "Regeneron Pharmaceuticals, Tarrytown, New York, USA"
      ],
      "name": "Matthew G Fury"
    },
    {
      "affiliations": [
        "Galapagos BV, Leiden, ZH, The Netherlands"
      ],
      "name": "Anna-Sophia Wiekmeijer"
    },
    {
      "affiliations": [
        "Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy"
      ],
      "name": "Lisa Licitra"
    },
    {
      "affiliations": [
        "Oncology, Palacky Univ, Olomouc, Czech Republic"
      ],
      "name": "Bohuslav Melichar"
    },
    {
      "affiliations": [
        "University Medical Center Utrecht, Cancer Center, Utrecht, The Netherlands"
      ],
      "name": "Lot A Devriese"
    },
    {
      "affiliations": [
        "Vall d’Hebron Institute of Oncology, Barcelona, Spain"
      ],
      "name": "Irene Braña"
    },
    {
      "affiliations": [
        "Somerset National Health Service, Taunton, UK"
      ],
      "name": "Petra Jankowska"
    },
    {
      "affiliations": [
        "Hematology/Oncology, Mount Sinai Health System, New York, New York, USA"
      ],
      "name": "Marshall Posner"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Bonnie Glisson"
    },
    {
      "affiliations": [
        "King's college London, London, Great Brittain"
      ],
      "name": "Anthony Kong"
    },
    {
      "affiliations": [
        "Barinthus Biotherapeutics plc, Harwell, England, UK"
      ],
      "name": "Leon Hooftman"
    },
    {
      "affiliations": [
        "ISAbella Pharma BV, Leiden, The Netherlands"
      ],
      "name": "Cornelis J M Melief, MD,"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Renata Ferrarotto"
    }
  ],
  "title": "Randomized clinical efficacy and safety study of peltopepimut-S plus cemiplimab compared to cemiplimab alone in patients with recurrent/metastatic HPV16-positive head and neck cancer",
  "uid": "9c39f66a-dfa1-5355-a85d-d29d4ef251e8"
}