{
  "abstract": "Background VAX014 is a novel, non-viral oncolytic immunotherapy based on recombinant bacterial minicells (rBMCs). 1 Unlike oncolytic virotherapies, VAX014 does not require BSL-2 containment and has optimal antitumor activity in tumors expressing the antiviral pattern recognition receptors, STING and/or RIG-I.2 VAX014 is being evaluated for intratumoral treatment of advanced solid tumors in a two-part multi-center Phase 1 study (NCT 05901285). The dose escalation component of the study is complete and the dose expansion portion giving VAX014 in combination with investigator’s choice of PD-1 inhibitor is being initiated.Methods Eligible patients (pts) have a performance status of 0-2 (ECOG), measurable disease, and at least 1 injectable advanced solid tumor (1-10 cm in longest diameter) accessible by either physical exam (dose escalation) or ultrasound or other image-guided injection of visceral tumor(s) (dose expansion). The dose escalation segment employed a 3+3 design with 5 planned dose cohorts. Dose escalation with weekly intratumoral administration of VAX014 will proceed until a maximum tolerated dose or maximum practical dose is reached.Dose expansion will evaluate VAX014 in combination with investigator’s choice of pembrolizumab (200mg/Q3weeks) or nivolumab (240mg/Q2weeks) in patients with solid tumors that have progressed on prior PD-1 therapy.The primary study objectives are to establish safety and tolerability. Secondary study objectives will evaluate pharmacokinetics, anti-drug antibody formation, changes in intratumoral and peripheral immune status, and response(s) in injected and non-injected lesions (per itRECIST) and overall response (per RECIST 1.1).Results As of 26-June-2025, 15 pts with advanced solid tumors have been treated with VAX014 monotherapy over 5 dose cohorts ranging from 4.0x10 6 to 4.0x108 VAX014 rBMCs (10 M/8 F, median age 61 (range, 35-81), median prior therapies 5 (range, 2-16), with 12 of 15 (80%) having prior PD-(L)1 inhibitor. No DLTs have been reported, and VAX014-related toxicity has been limited to Grade 1-2 adverse events.Thirteen of 15 (86.6%) pts had stable disease (SD) or better in injected tumors at any timepoint with 5/15 demonstrating ≥ 30% reduction from baseline (-60%, -53%, -48%, -38% and -32%). Three of 15 (20%) pts had SD or better at any time in noninjected tumors with 2 demonstrating ≥ 30% reduction (1 with 48% reduction, 1 completely resolved). The best overall response was SD (RECIST 1.1).Conclusions VAX014 monotherapy is well tolerated with evidence of activity in both injected and noninjected tumors across dose levels and will now be evaluated in combination with investigator’s choice of pembrolizumab or nivolumab during dose expansion.Trial Registration NCT 05901285References Reil KA, et al. Intralesional administration of VAX014 facilitates in situ immunization and potentiates immune checkpoint blockade in immunologically cold tumors. J Immunother Cancer 2023;11(6).Nelson KL, et al. VAX014 activates tumor-intrinsic STING and RIG-I to promote the development of antitumor immunity. Mol Cancer Ther. 2025;24(4):587–604.Ethics Approval This Phase 1 study obtained ethics approval via a central Institutional Review Board (WIRB; IRB No. 20232966) and/or the Institutional Review Board of each respective institution (Dana-Farber Cancer Institute, IRB No. 23-304; Cleveland Clinic, IRB No. 24-280; Dartmouth Hitchcock, IRB No. STUDY02002393). All participants in the study gave informed consent prior to enrollment.",
  "authors": [
    {
      "affiliations": [
        "The Skin Cancer Institute, Denver, CO, USA"
      ],
      "name": "Ryan M Weight"
    },
    {
      "affiliations": [
        "Sarah Cannon Research Institute at HealthONE, Denver, CO, USA"
      ],
      "name": "Gerald S Falchook"
    },
    {
      "affiliations": [
        "University of Arizona Cancer Center, Tucson, AZ, USA"
      ],
      "name": "Ricklie A Julian"
    },
    {
      "affiliations": [
        "Dana-Farber Cancer Institute, Boston, MA, USA"
      ],
      "name": "Elizabeth I Buchbinder"
    },
    {
      "affiliations": [
        "Atlantic Health System, Morristown, NJ, USA"
      ],
      "name": "Eric D Whitman"
    },
    {
      "affiliations": [
        "The George Washington University, Washington, DC, USA"
      ],
      "name": "Pavani Chalasani"
    },
    {
      "affiliations": [
        "Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA"
      ],
      "name": "Keisuke Shirai"
    },
    {
      "affiliations": [
        "Cleveland Clinic, Durham, NC, USA"
      ],
      "name": "James M Isaacs"
    },
    {
      "affiliations": [
        "University of Maryland, Baltimore, MD, USA"
      ],
      "name": "Katherine H Tkaczuk"
    },
    {
      "affiliations": [
        "SciQuus Oncology, San Diego, CA, USA"
      ],
      "name": "Teresa J Melink"
    },
    {
      "affiliations": [
        "SciQuus Oncology, San Diego, CA, USA"
      ],
      "name": "John Gutheil"
    },
    {
      "affiliations": [
        "Vaxiion Therapeutics, San Diego, CA, USA"
      ],
      "name": "Matthew J Giacalone"
    }
  ],
  "title": "615 Phase 1 study of intratumoral VAX014 with dose expansion in combination with pembrolizumab or nivolumab in patients with advanced solid tumors",
  "uid": "c4d26fbc-0c75-5216-85d4-307b77254b6c"
}