{
  "abstract": "Background This study evaluated the safety and feasibility of intrathecal programmed death 1 (PD-1) inhibitor plus pemetrexed for leptomeningeal metastases (LM) from solid tumors.Methods In phase I, a 3+3 dose de-escalation design determined dose-limiting toxicity (DLT) and the recommended dose for phase II. Patients received intrathecal pemetrexed (15 mg flat dose) twice weekly for 2 weeks (induction), then weekly for 4 weeks (consolidation), followed by monthly maintenance. Intrathecal PD-1 inhibitor (40 mg initial dose) was given every 2 weeks for 6 weeks (induction/consolidation), then monthly during maintenance. Selected patients received involved-field radiotherapy. Primary endpoints were recommended dose and safety based on adverse events (AEs). Clinical response rate (CRR), disease control rate (DCR) and overall survival (OS) were evaluated.Results From 6/2024 to 3/2025, 31 patients were enrolled (26 non-small cell lung cancer, 4 breast cancer, and 1 small cell lung cancer). At the initial dose level of phase I, 7 patients were enrolled. No DLT was observed. The recommended dose was intrathecal 40 mg PD-1 inhibitor plus 15 mg pemetrexed. All patients completed induction therapy, 27 completed consolidation therapy, and 28 received maintenance therapy. 14 patients received radiotherapy. No treatment-related deaths occurred. Grade ≥3 AEs occurred in 52% (16/31), primarily hematologic toxicity (n=14) and elevated hepatic aminotransferases (n=3). Grade 1–2 immune-related AEs occurred in 32% (10/31), including rash (n=5), fever (n=3), hypothyroidism (n=1), and pneumonia (n=1). CRR was 61% (19/31) per Response Assessment in Neuro-Oncology proposal criteria, including 8 neurological dysfunction improvements, 10 CSF cytological responses, and 11 neuroimaging improvements. 74% (23/31) of patients showed LM-related neurological symptoms improvement. DCR was 87% (27/31). As of 20 June 2025, 6 patients died. Median follow-up time was 5.9 (2.0-12.1) months. Median OS was not reached.Conclusions Intrathecal PD-1 inhibitor plus pemetrexed showed feasibility for LM from solid tumors with potential activity.Trial Registration ClinicalTrials.gov Identifier: NCT 06462222Ethics Approval This phase I/II study was conducted according to the Declaration of Helsinki, and was approved by the Institutional Review Board of the Affiliated Huizhou Hospital, Guangzhou Medical University, Huizhou, China (Approval number: 2024-KY-029-01). Informed consent was obtained from all subjects. (ClinicalTrials.gov Identifier: NCT 06462222)Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.",
  "authors": [
    {
      "affiliations": [
        "The Affiliated Huizhou Hospital, Guangzhou Medical University, Huizhou, Guangdong, China"
      ],
      "name": "Zhenyu Pan"
    },
    {
      "affiliations": [
        "The Affiliated Huizhou Hospital, Guangzhou Medical University, Huizhou, Guangdong, China"
      ],
      "name": "Guozi Yang"
    },
    {
      "affiliations": [
        "The Affiliated Huizhou Hospital, Guangzhou Medical University, Huizhou, Guangdong, China"
      ],
      "name": "Miaomiao Liu"
    },
    {
      "affiliations": [
        "The Affiliated Huizhou Hospital, Guangzhou Medical University, Huizhou, Guangdong, China"
      ],
      "name": "Yushan Huang"
    },
    {
      "affiliations": [
        "The Affiliated Huizhou Hospital, Guangzhou Medical University, Huizhou, Guangdong, China"
      ],
      "name": "Min Liu"
    },
    {
      "affiliations": [
        "The Affiliated Huizhou Hospital, Guangzhou Medical University, Huizhou, Guangdong, China"
      ],
      "name": "Panpan Tai"
    },
    {
      "affiliations": [
        "The Affiliated Huizhou Hospital, Guangzhou Medical University, Huizhou, Guangdong, China"
      ],
      "name": "Xiao Chen"
    },
    {
      "affiliations": [
        "The Affiliated Huizhou Hospital, Guangzhou Medical University, Huizhou, Guangdong, China"
      ],
      "name": "Yu Wu"
    },
    {
      "affiliations": [
        "The Affiliated Huizhou Hospital, Guangzhou Medical University, Huizhou, Guangdong, China"
      ],
      "name": "Xingru Sun"
    },
    {
      "affiliations": [
        "The Affiliated Huizhou Hospital, Guangzhou Medical University, Huizhou, Guangdong, China"
      ],
      "name": "Anyan Gu"
    }
  ],
  "title": "583 Intrathecal PD-1 inhibitor combined with pemetrexed for leptomeningeal metastases from solid tumors: preliminary results from a phase I/II study (NCT 06462222)",
  "uid": "1379dc19-7256-562f-888c-ae4831b0d76f"
}