{
  "abstract": "Background Evorpacept (evo) is a high-affinity CD47-blocking fusion protein with an inactive Fc domain designed to enhance anticancer antibody-dependent cellular phagocytosis in combination with other therapies. Previously, evo has demonstrated improved objective response, duration of response, and PFS in combination with trastuzumab (T), ramucirumab (R), and paclitaxel (P) in advanced, previously treated HER2+ gastric/gastroesophageal cancer (GC) in ASPEN-06. 1 Methods The ASPEN-06 randomized phase 2 trial assessed evo (30 mg/kq Q2W) + TRP vs. TRP in patients with 2nd or 3rd line HER2+ advanced or metastatic GC that had progressed on or after prior anti-HER2 therapy. CD47 expression was measured by immunohistochemistry (IHC), and HER2 status was determined per ASCO/CAP guidelines in the most recent GC tissue sample. ERBB2 amplification was also measured by ctDNA at baseline. Objective response (ORR) is presented by investigator per RECIST v1.1. ORR, PFS, and OS were analyzed by CD47 tumor membrane expression level, and results are based on a data cut-off date of May 15, 2025.Results Within the intent to treat randomized population (N=127), the majority of patients had available CD47 expression data (N=119) and confirmatory HER2 positivity, as determined by either fresh biopsy or ctDNA (N=90). Median follow up time was 22.1 months. Among patients with HER2+ tumors by either fresh biopsy or ctDNA, and with ≥10% of tumor cells exhibiting high-intensity membranous CD47 staining (48% of the sample), evo had greater clinical benefit; ORR was 65% (13/20; 95% CI: 41%-85%; evo-TRP) vs. 26% (6/23; 95% CI: 10%-48%; TRP) with hazard ratios for PFS of 0.37 (95% CI: 0.2-0.8) and OS of 0.66 (95% CI: 0.3-1.4). For patients with CD47 expression below this cut-off, ORR was 39% (9/23; 95% CI: 20%-61%; evo-TRP) and 25% (6/24; 95% CI: 10%-47%; TRP) with hazard ratios for PFS of 1.1 (95% CI: 0.5, 2.1) and OS of 1.3 (95% CI: 0.7-2.7). Results were similar for multiple cut-offs. Updated efficacy results across a range of cut-offs will be presented at the meeting.Conclusions Increased levels of CD47 membranous tumor expression were associated with greater clinical benefit of evo in combination with TRP in HER2+ GC. A biomarker-driven approach to patient selection could lead to improved efficacy for evo. Further evaluation of the potential for patient selection by CD47 for evo-based combinations in GC and other indications is warranted.Trial Registration ClinicalTrials.gov identifier NCT05002127Reference Shitara K et al. Final analysis of the randomized phase 2 part of the ASPEN-06 study: a phase 2/3 study of evorpacept (ALX148), a CD47 myeloid checkpoint inhibitor, in patients with HER2-overexpressing gastric/gastroesophageal cancer (GC). JCO. 2025;43:332-332.Ethics Approval The study was conducted in accordance with all relevant local/national regulatory requirements, the International Ethical Guidelines for Biomedical Research Involving Human Subjects and the Declaration of Helsinki. All research was approved by the relevant institutional review boards or ethics committees, and all patients provided written informed consent prior to study participation.",
  "authors": [
    {
      "affiliations": [
        "David Geffen School of Medicine at UCLA, Santa Monica, CA, USA"
      ],
      "name": "Zev A Wainberg"
    },
    {
      "affiliations": [
        "Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea"
      ],
      "name": "Keun-Wook Lee"
    },
    {
      "affiliations": [
        "Vall d’Hebron University Hospital and Institute of Oncology (VHIO), Barcelona, Spain"
      ],
      "name": "Josep Tabernero"
    },
    {
      "affiliations": [
        "University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium"
      ],
      "name": "Eric Van Cutsem"
    },
    {
      "affiliations": [
        "Centre Léon Bérard, Lyon, France"
      ],
      "name": "Clélia Coutzac"
    },
    {
      "affiliations": [
        "Institut Paoli-Calmettes, Marseilles, France"
      ],
      "name": "Christelle de la Fouchardière"
    },
    {
      "affiliations": [
        "Samsung Medical Center, Seoul, Republic of Korea"
      ],
      "name": "Jeeyun Lee"
    },
    {
      "affiliations": [
        "Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea"
      ],
      "name": "Sun Young Rha"
    },
    {
      "affiliations": [
        "Asan Medical Center, Seoul, Republic of Korea"
      ],
      "name": "Yoon-Koo Kang"
    },
    {
      "affiliations": [
        "ALX Oncology Inc., South San Francisco, CA, USA"
      ],
      "name": "Charlie Zhang"
    },
    {
      "affiliations": [
        "ALX Oncology Inc., South San Francisco, CA, USA"
      ],
      "name": "Daniel Brickman"
    },
    {
      "affiliations": [
        "ALX Oncology Inc., South San Francisco, CA, USA"
      ],
      "name": "Philip Fanning"
    },
    {
      "affiliations": [
        "ALX Oncology Inc., South San Francisco, CA, USA"
      ],
      "name": "Alison J Forgie"
    },
    {
      "affiliations": [
        "ALX Oncology Inc., South San Francisco, CA, USA"
      ],
      "name": "Athanasios C Tsiatis"
    },
    {
      "affiliations": [
        "ALX Oncology Inc., South San Francisco, CA, USA"
      ],
      "name": "Alan Sandler"
    },
    {
      "affiliations": [
        "National Cancer Hospital East, Kashiwa-shi, Japan"
      ],
      "name": "Kohei Shitara"
    }
  ],
  "title": "496 CD47 expression as a predictive biomarker for evorpacept in HER2-positive gastric/gastroesophageal cancer from the Phase 2 randomized ASPEN-06 trial",
  "uid": "30a8af04-202d-58cc-8a08-f09fa2f2d736"
}