{
  "abstract": "Background H3K27M-mutant diffuse midline gliomas (DMGs) are highly aggressive central nervous system tumors characterized by resistance to conventional therapies and low immunogenicity. Consequently, there is a pressing need for novel therapeutic strategies to improve patient outcomes. Recent studies highlight the importance of combinatorial treatment approaches, refined patient stratification, and an enhanced understanding of the brain tumor immune microenvironment. Among emerging strategies, combining immune checkpoint inhibitors with targeted therapies has shown potential to overcome intrinsic resistance mechanisms. Ivonescimab, a novel bispecific antibody that simultaneously targets PD-1 and VEGF, represents one such promising approach. By inhibiting PD-1, Ivonescimab restores T-cell-mediated antitumor immunity, while VEGF blockade suppresses angiogenesis. Preclinical data suggest a synergistic mechanism, with VEGF enhancing PD-1 binding affinity by more than 18-fold and vice versa, supporting cooperative dual targeting. To date, no clinical trials have evaluated Ivonescimab in the treatment of DMG, which was administered as salvage therapy.Methods A 24-year-old male was diagnosed with recurrent H3K27M+ DMG. Histopathological examination and immunophenotyping confirmed the diagnosis. Molecular analysis demonstrated positive MGMT promoter methylation, while IDH1/2 and TERT mutations were negative. The patient initially underwent focal radiotherapy (60 Gy in 30 fractions) with concurrent temozolomide as first-line treatment. Eight months postoperatively, he presented with progressive ataxia and somnolence. Follow-up magnetic resonance imaging (MRI) revealed radiographic evidence of tumor progression. Given the rapid clinical deterioration and lack of standard salvage therapies, off-label treatment with Ivonescimab was initiated. The patient received Ivonescimab at a dose of 10 mg/kg (500 mg) every three weeks for a total of five cycles, following informed consent ( figure 1).Results After three cycles of Ivonescimab, follow-up MRI performed at week-9 revealed a marked reduction in tumor size. Concurrently, the patient‘s Karnofsky Performance Status (KPS) improved significantly, increasing from 40 to 80. After completing five cycles (week 15), MRI demonstrated complete remission (CR), as assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 ( figure 2). The treatment was well tolerated. No Grade 3 or higher adverse events were observed during the treatment period, based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.Conclusions Although earlier clinical trials reported limited efficacy of immunotherapy in high-grade gliomas, the present study demonstrates that dual-targeted therapy, which integrating anti-angiogenic agents with PD-1 inhibition, achieves unexpectedly favorable results, indicating a notable synergistic effect. This strategy represents a promising new immunotherapeutic avenue for the treatment of diffuse midline glioma.Abstract 440 Figure 1Treatment time tableAbstract 440 Figure 2MRI images. A. Before surgery; B. Eight months post-surgery, lesion recurred; C. Ivonescimab treatment for 3 cycles; D. Ivonescimab treatment for 5 cycles",
  "authors": [
    {
      "affiliations": [
        "West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Li Yanchu"
    },
    {
      "affiliations": [
        "West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Yang Yuan"
    },
    {
      "affiliations": [
        "West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Zhang Li"
    },
    {
      "affiliations": [
        "West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Zhao Gang"
    },
    {
      "affiliations": [
        "No.1 People’s Hospital of Liangshan, Liangshan, Sichuan, China"
      ],
      "name": "Yuan Xiaoli"
    },
    {
      "affiliations": [
        "West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Ren Meiling"
    },
    {
      "affiliations": [
        "West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Wang Feng"
    }
  ],
  "title": "440 The combined action of anti-PD-1/VEGF bispecific antibody for inhibition recurrent H3K27M+ diffuse midline gliomas: a pilot case report of Ivonescimab in a DMG patient",
  "uid": "6467aeed-994e-53bc-865c-9e0e5f2ea093"
}