{
  "abstract": "Purpose ASP9801, an oncolytic virus encoding interleukin-7 and interleukin-12, was assessed for safety, tolerability, pharmacokinetics, and antitumor activity in patients with advanced solid tumors in a Phase 1 study.Methods The study comprised Part 1 ASP9801 monotherapy dose escalation and Part 2 dose expansion with ASP9801 monotherapy or plus pembrolizumab. Each part was divided into Groups A (ASP9801 injection into cutaneous/subcutaneous lesions) and B (ASP9801 injection into visceral lesions). Primary objectives were safety and maximum tolerated dose and/or recommended Phase 2 dose expansion (RP2D); secondary objectives included antitumor activity and pharmacokinetics.Results In dose escalation, 17 and 10 patients in Groups A and B, respectively, received treatment. One dose-limiting toxicity (DLT; grade 3 cytokine release syndrome) was reported in Group A. Treatment-related adverse events (TRAEs) in ≥30% of patients in Group A were pyrexia and in Group B were pyrexia, chills, vomiting, nausea, fatigue, and headache. AEs leading to death occurred in two patients in Group A (one each for malignant neoplasm progression and sepsis); neither was attributed to ASP9801. The RP2D of ASP9801 was 5×10 8 plaque-forming unit/mL. In Part 2 dose expansion Group A, 12 patients received monotherapy RP2D, 5 received monotherapy induction, and 2 received ASP9801 plus pembrolizumab. In Group B, 9 and 11 patients received ASP9801 monotherapy or plus pembrolizumab, respectively. One DLT occurred in Group B combination safety cohort (grade 2 pyrexia and mental status change; grade 3 hypoxia, lymphopenia, and pneumonitis). During dose expansion, TRAEs in ≥30% of any cohort (>1 patient) in Group A were nausea, fatigue, chills, pyrexia, and headache and in Group B were nausea, vomiting, fatigue, chills, pyrexia, and lymphocyte count decreased. AEs led to death in two patients in Group A monotherapy and one patient in Group B monotherapy cohorts, all due to malignant neoplasm progression; none were attributed to ASP9801. One patient in Group B combination safety cohort achieved confirmed partial response (objective response rate, 9.1% (95% CI 0.3% to 52.7%)).Conclusions Treatment with ASP9801 alone or plus pembrolizumab was generally well tolerated; however, the study was stopped due to lack of efficacy during dose expansion.",
  "authors": [
    {
      "affiliations": [
        "Departments of Medicine, Neurosurgery, and Neurology, University of Kentucky College of Medicine, Lexington, Kentucky, USA"
      ],
      "name": "John L Villano"
    },
    {
      "affiliations": [
        "UPMC Hillman Cancer Center, and Division of Malignant Hematology and Medical Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"
      ],
      "name": "Jason J Luke"
    },
    {
      "affiliations": [
        "Arizona Cancer Center and Department of Medicine, University of Arizona, Tucson, Arizona, USA"
      ],
      "name": "Ricklie Julian"
    },
    {
      "affiliations": [
        "Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA"
      ],
      "name": "Christos Fountzilas"
    },
    {
      "affiliations": [
        "Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota, USA"
      ],
      "name": "Manish R Patel"
    },
    {
      "affiliations": [
        "Merck & Co., Inc, Rahway, New Jersey, USA"
      ],
      "name": "Michael J Chisamore"
    },
    {
      "affiliations": [
        "Astellas Pharma Inc, Northbrook, Illinois, USA"
      ],
      "name": "Pranob Bhattacharya"
    },
    {
      "affiliations": [
        "Astellas Pharma Inc, Northbrook, Illinois, USA"
      ],
      "name": "Shigeru Takeshita"
    },
    {
      "affiliations": [
        "Astellas Pharma Inc, Northbrook, Illinois, USA"
      ],
      "name": "Serguei Soukharev"
    },
    {
      "affiliations": [
        "Astellas Pharma Inc, Tokyo, Japan"
      ],
      "name": "Shunsuke Yamada"
    },
    {
      "affiliations": [
        "Astellas Pharma Inc, Beijing, China"
      ],
      "name": "Leshi Zhang"
    },
    {
      "affiliations": [
        "The Angeles Clinic and Research Institute, Los Angeles, California, USA"
      ],
      "name": "Kristopher P Wentzel"
    }
  ],
  "title": "Phase 1 open-label study of ASP9801, an oncolytic virus, in patients with advanced or metastatic solid tumors",
  "uid": "3c0b5ce5-1834-53c8-9258-d6f5168485a3"
}