{
  "abstract": "Background Immune checkpoint-targeted antibodies directed at PD-1 or PD-L1 block co-inhibitory receptors expressed by anti-tumor T cells, breaking immune tolerance against tumor cells and generating cancer immunity. Immunotherapy by intratumoral (IT) injection aims to use the tumor as a ‘self-vaccine’, stimulating local immune activation and priming an anti-tumor immune response. This may generate abscopal tumor responses, activating untreated tumors via circulating activated anti-tumor immune cells. Local delivery of immunotherapy minimizes systemic exposure and off-target toxicities and may decrease tumor size and improve surgical morbidity.The INTASYL™ compound PH-762 is designed to precisely silence PD-1 mRNA. INTASYL is a patented, self-delivering RNAi technology designed to impart specific properties to small interfering RNAs. INTASYL’s unique structural and chemical modifications ensure optimized cell and tissue uptake of PH-762 with IT administration. The efficient uptake of PH-762 by human T cells, silencing of PD-1 mRNA and subsequent protein reduction has been demonstrated preclinically. Murine-targeted PH-762 (mPH-762) injections can silence PD-1 mRNA in T cells within the murine tumor and increase the secretion of IFN-γ.Methods This open-label Phase 1 clinical study (NCT 06014086) is designed to evaluate the safety and tolerability of neoadjuvant use of IT PH-762 in cutaneous squamous cell carcinoma, melanoma, or Merkel cell carcinoma, to determine the pharmacokinetic profile of PH-762 after IT injection, to observe pathologic and immunologic tumor responses, and to determine the recommended dose for development. Eligible tumors are at least 1.0 cm and no more than 3.0 cm in longest dimension. Escalating dose concentrations of PH-762 (from 1.14 mg/mL through 22.00 mg/mL) are tested serially in cohorts of 3 patients each. Patients receive IT PH-762 once weekly, 4 times over a 3-week period prior to surgical excision, which occurs 5 weeks after the initial injection. Tumor changes are evaluated per iRECIST criteria and pathological response.Trial Registration Clinicaltrials.gov: NCT 06014086Ethics Approval This study was approved by Advarra Institutional Review Board (00023875).",
  "authors": [
    {
      "affiliations": [
        "Panclarity LLC, San Francisco, CA, USA"
      ],
      "name": "Mary C Spellman"
    },
    {
      "affiliations": [
        "Prosoft Clinical, Chesterbrook, PA, USA"
      ],
      "name": "Katharine W Furst"
    },
    {
      "affiliations": [
        "Phio Pharmaceuticals Corp., King of Prussia, PA, USA"
      ],
      "name": "Linda Mahoney"
    }
  ],
  "title": "610 PD-1-directed intratumoral immunotherapy for cutaneous carcinomas: a clinical study of INTASYL PH-762",
  "uid": "b2988e1c-aef7-5f9d-bd95-65586375ef54"
}