{
  "abstract": "Background PBA-0405 is a novel FIH monoclonal antibody therapy targeting ROR-1 expressing hematological and solid tumors with enhanced Fc gamma receptor (FcγRIII, CD16) binding to amplify NK cell and Macrophage ADCC/ADP activity. ROR1 receptor expression is largely absent in healthy adult tissues, making it an ideal target for antibody-based therapy. To confirm the mechanisms of action and efficacy of PBA-0405 in solid tumors, a first in human (FIH) CIVO microdose study was conducted in patients with either Head and Neck squamous cell carcinoma (HNSCC) or Soft Tissue Sarcoma (STS). Following CIVO intratumoral microdose injections of PBA-0405 directly in patient tumors in vivo, localized biomarkers of drug activity were evaluated across resected patient tumor samples revealing localized induction of interferon in tumors that were ROR-1+ with CD16+ immune cell infiltrate.Methods The PBA-0405 multicenter Ph0 study has been completed (APR2024 to Feb2025). Enrolled subjects had a confirmed diagnosis of HNSCC or STS with planned surgical resection of a surface-accessible primary or metastatic tumor. The CIVO intratumoral microdoses for this study consisted of a fluorescent microsphere injection site tracking marker co-formulated with either vehicle or PBA-0405. Microdoses were administered via CIVO simultaneous multiplexed injection 24 to 48 hours before tumor resection. Surgically resected tumor samples were formalin fixed and shipped to Presage Biosciences where they were embedded, processed, and analyzed using multiplex immunohistochemistry assays that read out on biomarkers and pathways of tumor and immune cell response.Results The study was completed with eight patients enrolled. Six tumor samples were of sufficient quality for biomarker analysis. CIVO injection procedure was well tolerated and no CIVO or drug-related adverse effects were reported. Interferon pathway activation including induction of CXCL10 and/or ISG15 was evident at PBA-0405 injection sites with ROR1 target expression and CD16+ immune cell infiltrate. An increase in apoptosis measured by an increase in cleaved caspase 3 (CC3) staining was seen at the sites of PBA-0405 drug exposure where interferon pathway activation was observed.Conclusions This FIH study of the novel anti-ROR1 monocloncal antibody, PBA-0405, illustrates the potential of this drug to induce immune cell mediated tumor killing in solid tumor indications. Based on the findings from this early phase CIVO microdose study, further clinical development of PBA-0405 for the treatment of ROR1 expressing solid tumors is warranted.Ethics Approval This study was approved by the Institutional Review Boards of the University of Pennsylvania (approval #855699), and WCG (approval #20240440). All patients gave informed consent before taking part.",
  "authors": [
    {
      "affiliations": [
        "Oregon Health and Science University, Portland, OR, USA"
      ],
      "name": "Kenneth Gundle"
    },
    {
      "affiliations": [
        "Louisiana State University Health Shreveport, Shreveport, LA, USA"
      ],
      "name": "John Pang"
    },
    {
      "affiliations": [
        "Sarah Cannon Cancer Institute, Charleston, SC, USA"
      ],
      "name": "Jeffrey Houlton"
    },
    {
      "affiliations": [
        "University of Pennsylvania, Philadelphia, PA, USA"
      ],
      "name": "Karthik Rajasekaran"
    },
    {
      "affiliations": [
        "Pure Biologics, Wroclaw, Poland"
      ],
      "name": "John Weinberg"
    },
    {
      "affiliations": [
        "Pure Biologics, Wroclaw, Poland"
      ],
      "name": "Niina Veitonmaki"
    },
    {
      "affiliations": [
        "Presage Biosciences, Inc., Seattle, WA, USA"
      ],
      "name": "Connor Burns"
    },
    {
      "affiliations": [
        "Presage Biosciences, Inc., Seattle, WA, USA"
      ],
      "name": "Atticus Turner"
    },
    {
      "affiliations": [
        "Presage Biosciences, Inc., Seattle, WA, USA"
      ],
      "name": "Angela Merrell"
    },
    {
      "affiliations": [
        "Presage Biosciences, Inc., Seattle, WA, USA"
      ],
      "name": "Marc Grenley"
    },
    {
      "affiliations": [
        "Presage Biosciences, Inc., Seattle, WA, USA"
      ],
      "name": "Jason Frazier"
    },
    {
      "affiliations": [
        "Pure Biologics, Wroclaw, Poland"
      ],
      "name": "Pieter Spee"
    }
  ],
  "title": "501 A first in human phase 0 microdose study with the novel anti-ROR1 antibody (PBA-0405) in patients with solid tumors of soft tissue sarcoma and head and neck cancer",
  "uid": "fbccd470-7af1-5711-b16c-5fa461aecbc9"
}