{
  "abstract": "Background Limited efficacy of conventional therapies in advanced solid tumors has driven interest in novel immunotherapies, including oncolytic viruses (OV). ASP1012 is a double-stranded DNA OV expressing C-C chemokine receptor 2 and a human leptin-interleukin-2 (IL-2) fusion protein that selectively replicates in cancer cells, causing cell lysis and enhanced antitumor immune responses via IL-2. ASP1012 is in development for locally advanced or metastatic (la/m) solid tumors in a first-in-human, Phase 1, open-label, multicenter study ( NCT06171178).Methods This study consisted of dose escalation and dose expansion parts ( figure 1). Eligible patients had measurable disease by RECIST v1.1 with ≥1 biopsy site, ECOG-PS of 0/1, and histologically/cytologically confirmed diagnosis of la/m solid tumors ineligible for surgical/medical treatment with curative intent, who progressed on or were ineligible for standard therapy. ASP1012 monotherapy was administered intravenously at 3×108, 1×109, and 3×109 pfu on days 1, 8, and 15 of ≤3 21-day treatment cycles until experiencing a DLT or ≥1 discontinuation criteria. Primary objective was safety and tolerability of ASP1012 at the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Treatment-emergent adverse events (TEAE) were collected through 30 days post-final ASP1012 dose and graded by NCI CTCAE v5.0. Secondary objectives were antitumor effects per immune-based (i)RECIST by investigator assessment.Results For dose escalation, 15 patients were enrolled and received ≥1 dose of ASP1012: 3×10 8 (n=2), 1×109 (n=7), and 3×109 pfu (n=6). Nine patients were male and median (range) age was 59 years (20–90). Median (range) duration of treatment was 8 weeks (1–37). At data cutoff of May 22, 2025, 7 patients had discontinued treatment due to consent withdrawal (n=4), disease progression (n=2), or adverse events (n=1). All patients experienced ≥1 TEAE, most commonly cytokine release syndrome (n=9), nausea (n=6), and chills (n=6) (table 1). Grade ≥3 TEAEs occurred in 8 patients, most commonly pneumonia (n=2) and aspartate aminotransferase increased (n=2). One patient each experienced TEAEs of pneumonia (dose: 3×108; not considered treatment-related) and viral infection (dose: 3×109; considered treatment-related and a DLT) that led to withdrawal of ASP1012. A second DLT occurred (dose: 3×109) of prolonged grade 3 elevated liver transaminases. Two deaths occurred due to disease progression. Among 11 response-evaluable patients, 4 had best overall response of confirmed stable disease per iRECIST and disease control rate (95% CI) was 36.4% (10.9%–69.2%).Conclusions ASP1012 demonstrated a tolerable and manageable safety profile up to and including 3×10 9 pfu/dose.Acknowledgements This study was funded by Astellas Pharma Inc. Medical writing support, conducted in accordance with Good Publication Practice (GPP 2022) and the International Committee of Medical Journal Editors (ICMJE) guidelines, was provided by Dolly Alkoborssy, PhD, of Oxford PharmaGenesis Inc., Wilmington, DE, USA, and funded by Astellas Pharma Inc.Trial Registration clinicaltrials.gov - NCT06171178Ethics Approval This study received IRB approval from Western Institutional Review Board - Copernicus Group and Institutional Review Boards (Approval numbers: 1-1754242-1; STUDY00002345/P-3713323; 202310303; 1-1786751-1; 1-1758102-1; 1-1715602-1; 1-1732476-1; 1-1718237-1; 1-1727742-1).Abstract 520 Figure 1Study designAbstract 520 Table 1Treatment-emergent adverse events occurring in ≥10% of the safety analysis population; dose-escalation cohort",
  "authors": [
    {
      "affiliations": [
        "Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA"
      ],
      "name": "Anthony F Shields"
    },
    {
      "affiliations": [
        "Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA"
      ],
      "name": "Douglas Laux"
    },
    {
      "affiliations": [
        "Hoag Family Cancer Institute, Hoag Memorial Hospital Presbyterian, Newport Beach, CA, USA"
      ],
      "name": "Carlos Becerra"
    },
    {
      "affiliations": [
        "Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA"
      ],
      "name": "Benjamin Switzer"
    },
    {
      "affiliations": [
        "Astellas Pharma Inc., Northbrook, IL, USA"
      ],
      "name": "Yohei Okada"
    },
    {
      "affiliations": [
        "Astellas Pharma Inc., Northbrook, IL, USA"
      ],
      "name": "Toru Kakinuma"
    },
    {
      "affiliations": [
        "Astellas Pharma Inc., Northbrook, IL, USA"
      ],
      "name": "Gerald Koelsch"
    },
    {
      "affiliations": [
        "Astellas Pharma Inc., Northbrook, IL, USA"
      ],
      "name": "Ziwen Wei"
    },
    {
      "affiliations": [
        "Astellas Pharma Inc., Northbrook, IL, USA"
      ],
      "name": "Paul Lee"
    },
    {
      "affiliations": [
        "Astellas Pharma Inc., Northbrook, IL, USA"
      ],
      "name": "Markus Vallaster"
    },
    {
      "affiliations": [
        "Emory University School of Medicine, Atlanta, GA, USA"
      ],
      "name": "Olumide Gbolahan"
    }
  ],
  "title": "520 Safety and tolerability of ASP1012, an oncolytic virus, in adults with locally advanced or metastatic solid tumors: Results from a first-in-human, phase 1, open-label, dose-escalation study",
  "uid": "f507b86a-a125-57d8-b859-acc9d45effe2"
}