{
  "abstract": "Background FL115 is an engineered IL-15/IL15Rα-Fbody fusion protein, in which Fbody is a single-chain Fc designed to eliminate classical Fc effects including ADCC/CDC/ADCP while retaining FcRn engagement. It aims to enhance anti-tumor immunity via IL-15-mediated signaling on NK and CD8 + T cells while minimizing complexity from Fc. Here we present the preliminary safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy results from an ongoing phase 1 study of FL115 in patients with advanced solid tumors.Methods The phase 1 study enrolled patients (pts) aged ≥18 years with advanced solid tumors, ECOG 0/1. FL115 was administered via intravenous infusion QW in six cohorts (3, 10, 30, 45, 60, 90 ug/kg). Primary objectives were to determine safety and tolerability of FL115 monotherapy and maximum tolerated dose (MTD).Results As of August 21, 2025, 20 eligible patients were enrolled. MTD has not been reached. Most adverse events (AEs) were mild (grade 1–2) and recoverable. The safety profile of FL115 was consistent with cytokine-based therapies and underlying conditions of patients. One patient at 30 ug/kg experienced a Grade 3 drug-related cytokine release syndrome at Day 1 and recovered at Day 2 with routine supportive care alone, without the need for vasopressor treatment or low-flow nasal cannula or tocilizumab. Three patients experienced Grade 3 AEs possibly related to FL115, including aspartate aminotransferase increased (2 patients at 30ug/kg) and atrial fibrillation (1 patient at 60ug/kg). No Grade 4 or 5 AEs were reported.Among 17 efficacy evaluable patients, 2 (12%; both≥3L prior treatments) achieved partial responses, 4 (24%) had stable disease and 1 (6%) had non-CR/non-PD. PK showed FL115 exposure follow a dose-proportional manner, with average Cmax of 1435ng/ml at 90ug/kg. Peripheral blood PD showed FL115-driven dose-dependent expansion of NK cells (up to 8.1X over baseline), and CD8+ T cells (up to 3.9X over baseline), persisting throughout treatment with the longest observation in Cycle 5 and still ongoing.An essentially identically designed Phase 1 study of FL115 was conducted in US and similar trends were observed.Conclusions FL115 is the first IL-15 superagonist reporting PR as monotherapy in heavily-pretreated patients. Based on the data and MOA, Phase 1 studies of FL115 (IV infusion and subcutaneous injection) in combination with anti-PD1 antibody will be initiated shortly.Trial Registration This study was prospectively registered at ClinicalTrials.gov (Identifier: NCT07131189).Ethics Approval This study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Prior to study initiation, ethics approval was obtained from the institutional review boards (IRBs)/ethics committees of all three participating centers: [Sun Yat-sen University Cancer Center, Approval No.SL-A2023-111-02], [Shandong Cancer Hospital and Institute, Shandong First Medical University, Approval No.SDZLEC2024-205-01], and [Peking University Cancer Hospital, Approval No.2024YW116]. All participants provided written informed consent before enrollment.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": [
        "Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China"
      ],
      "name": "Hongyun Zhao"
    },
    {
      "affiliations": [
        "Peking University Cancer Hospital, Beijing, China"
      ],
      "name": "Xiangjuan Ma"
    },
    {
      "affiliations": [
        "Shandong Cancer Hospital and Institute, Shandong First Medical University, Jinan, Shandong, China"
      ],
      "name": "Qi Dang"
    },
    {
      "affiliations": [
        "Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China"
      ],
      "name": "Yuxiang Ma"
    },
    {
      "affiliations": [
        "Peking University Cancer Hospital, Beijing, China"
      ],
      "name": "Jian Fang"
    },
    {
      "affiliations": [
        "Shandong Cancer Hospital and Institute, Shandong First Medical University, Jinan, Shandong, China"
      ],
      "name": "Yuping Sun"
    },
    {
      "affiliations": [
        "Suzhou Forlong Biotechnology Co., LTD., Shanghai, China"
      ],
      "name": "Dong Wei"
    },
    {
      "affiliations": [
        "Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China"
      ],
      "name": "Li Zhang"
    }
  ],
  "title": "1334 Preliminary safety, pharmacokinetics, pharmacodynamics, and efficacy of FL115, a novel IL-15 superagonist, from a phase 1 study in patients with advanced solid tumors",
  "uid": "e982867c-3fda-50c3-96b5-c7e649d85f2b"
}