{
  "abstract": "Background Treatment options for melanoma that has progressed on anti-PD-1 therapy are limited. Vusolimogene oderparepvec (RP1) is a fusion-enhanced HSV-1-based oncolytic immunotherapy. The IGNYTE trial showed that RP1 in combination with nivolumab (nivo) demonstrated clinically meaningful, durable responses (objective response rate, 32.9%; median duration of response, 33.7 months by RECIST 1.1) in patients with anti-PD-1-failed melanoma, with mainly grade 1/2 constitutional-type side effects. The trial allowed retreatment with RP1 for patients deriving clinical benefit. Here, we present the investigator assessment of patients who were retreated with RP1 in the IGNYTE trial.Methods Patients with melanoma and confirmed progression on anti-PD-1 ± anti-CTLA-4 therapy for ≥8 weeks as the last prior treatment were enrolled. During the initial course, RP1 was given intratumorally at 1×10 6 PFU/mL initially, then at 1×107 PFU/mL Q2W (≤7 doses) with intravenous nivo (240 mg). Nivo was then given alone (240 mg Q2W or 480 mg Q4W) for 2 years. Retreatment with RP1 could occur if patients had injectable lesions, stable performance status, and no treatment-related grade 4 adverse events (AEs) or grade 3 injection-site reactions, infections, or immune-mediated AEs lasting >14 days. Additional doses of RP1 were administered at 1x107 PFU/mL Q2W either in combination with nivo or as monotherapy if nivo was stopped due to nivo-related toxicity. An investigator survey was performed to assess efficacy and safety in patients who received retreatment with RP1.Results Of 140 enrolled patients, 25 (18%) were retreated with RP1 after the first course of therapy (range, 1–24 additional doses). Of these, 17 patients experienced clinical benefit as determined by the investigator. Reasons for further treatment included aiming for deepening of response or delay of disease progression. Observed anti-tumor effects included complete resolution of new lesions (n = 1 patient) and deepened response (n = 4 patients). Five patients reported at least one grade ≥3 treatment-emergent AE, most of which were deemed not related to RP1.Conclusions Retreatment with RP1 demonstrated investigator-assessed clinical benefit in the majority of patients to whom it was given (17/25 patients; 68%). Retreatment was well tolerated with the safety profile being consistent with that of the study overall. Additional clinical data from this collection of case reports will be presented.Trial Registration ClinicalTrials.gov NCT03767348Ethics Approval The study was conducted in accordance with the ethical principles originating from the Declaration of Helsinki and was approved by the institutional review board/ethics committee at each participating site. Written informed consent was obtained from all patients prior to the conduct of any study-related procedures.",
  "authors": [
    {
      "affiliations": [
        "University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, USA"
      ],
      "name": "Gino K In"
    },
    {
      "affiliations": [
        "Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA"
      ],
      "name": "Michael K Wong"
    },
    {
      "affiliations": [
        "The Clatterbridge Cancer Centre, Wirral, UK",
        "University of Liverpool, Liverpool, UK"
      ],
      "name": "Joseph J Sacco"
    },
    {
      "affiliations": [
        "Vall d’Hebron Institute of Oncology (VHIO) and Vall d’Hebron Hospital Medical Oncology Department, Barcelona, Spain"
      ],
      "name": "Eva Muñoz Couselo"
    },
    {
      "affiliations": [
        "Department of Dermatology, West German Cancer Center, University Hospital Essen, Essen, Germany",
        "National Center for Tumor Diseases (NCT-West), Campus Essen and University Alliance Ruhr, Research Alliance Ruhr, Research Center One Health, University Duisburg-Essen, Campus Essen, Essen, Germany"
      ],
      "name": "Dirk Schadendorf"
    },
    {
      "affiliations": [
        "Duke Cancer Institute, Duke University, Durham, NC, USA"
      ],
      "name": "Georgia M Beasley"
    },
    {
      "affiliations": [
        "Banner MD Anderson Cancer Center, Gilbert, AZ, USA"
      ],
      "name": "Jiaxin Niu"
    },
    {
      "affiliations": [
        "Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA"
      ],
      "name": "Bartosz Chmielowski"
    },
    {
      "affiliations": [
        "University of Cincinnati Cancer Center, University of Cincinnati, Cincinnati, OH, USA"
      ],
      "name": "Trisha M Wise-Draper"
    },
    {
      "affiliations": [
        "Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA"
      ],
      "name": "Mohammed M Milhem"
    },
    {
      "affiliations": [
        "Intermountain Medical Center, Murray, UT, USA"
      ],
      "name": "Tawnya Lynn Bowles"
    },
    {
      "affiliations": [
        "Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA"
      ],
      "name": "Katy K Tsai"
    },
    {
      "affiliations": [
        "Université Paris Cité, AP-HP Dermato-Oncology and CIC, Cancer Institute AP-HP. Nord-Université Paris Cité, INSERM U976, Saint Louis Hospital, Paris, France"
      ],
      "name": "Céleste Lebbé"
    },
    {
      "affiliations": [
        "Aix-Marseille Université, APHM, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS, UMR7258, UM105, Hôpital Timone, CEPCM, Dermatology and Skin Cancer Department, Marseille, France"
      ],
      "name": "Caroline Gaudy-Marqueste"
    },
    {
      "affiliations": [
        "Leeds Institute of Medical Research at St. James’s, University of Leeds, Leeds, UK"
      ],
      "name": "Adel Samson"
    },
    {
      "affiliations": [
        "Replimune, Inc., Woburn, MA, USA"
      ],
      "name": "Junhong Zhu"
    },
    {
      "affiliations": [
        "Replimune, Inc., Woburn, MA, USA"
      ],
      "name": "Chris Tucci"
    },
    {
      "affiliations": [
        "Replimune, Inc., Woburn, MA, USA"
      ],
      "name": "Marcus Viana"
    },
    {
      "affiliations": [
        "Replimune, Inc., Woburn, MA, USA"
      ],
      "name": "Jeannie W Hou"
    },
    {
      "affiliations": [
        "Gustave Roussy and Paris-Saclay University, Villejuif, France"
      ],
      "name": "Caroline Robert"
    }
  ],
  "title": "600 Retreatment with RP1 in combination with nivolumab in patients with advanced anti-PD-1-failed melanoma",
  "uid": "efc52d83-f4b5-558d-bfa7-88a3d0f07239"
}