{
  "abstract": "Background TU2218 is a low molecular weight dual kinase inhibitor highly specific to TGFβR1 and VEGFR2 and has a potential to be an anti-cancer therapy by enhancing the tumor-killing effect of anti PD-(L)1 antibody. The inhibition of TGFβR1 and VEGFR2 remodels the immunosuppressive and fibrotic tumor microenvironment leading to tumor growth and metastasis limit, and may overcome therapeutic resistance to immune checkpoint inhibitors including anti PD-(L)1 antibody.Two Phase 1 trials evaluating TU2218 monotherapy and in combination with Pembrolizumab in patients with advanced solid tumors demonstrated acceptable level of safety and tolerability across all dose levels. The Recommended Phase 2 Dose of TU2218 was established at 195 mg/day in combination with Pembrolizumab. Subsequently, the trial was expanded to phase 2a trial in patients with head and neck squamous cell carcinoma (HNSCC) and two other cancer types.Methods This open-label, non-randomized, multinational, multicenter Phase 2a trial enrolled patients aged ≥18 years with ECOG performance status 0 or 1 and measurable disease. Eligible patients had either anti PD-(L)1 inhibitor-naïve metastatic or unresectable recurrent HNSCC with PD-L1 expression (CPS ≥1) confirmed by FDA-approved assay, or recurrent/metastatic HNSCC with disease progression after platinum-containing chemotherapy. The enrolled patients received TU2218 195 mg/day (97.5 mg BID) on 2-weeks-on/1-week-off schedule, and Pembrolizumab 200 mg intravenously every 3 weeks. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1.Results As of June 20, 2025 data cutoff, 18 patients had been enrolled and 12 patients were evaluable for efficacy. Among 12 evaluable patients, 8 patients achieved PR (66.7%), 1 patient maintained SD (8.3%), and 3 patients progressed disease (25%). The most frequently observed ≥ Grade 3 TRAE in all dosed patients were mucositis (16.7%), rash (22.2%) and no Grade 5 AE was reported.The evaluable patients were aged 43 ~ 72 years (average age: 60.7) and 75% of patients were male. The most common primary tumor locations were oropharynx (25%), oral cavity (16.7%), hypopharynx (16.7%).Conclusions TU2218 in combination with Pembrolizumab in patients with HNSCC demonstrated high response rate and manageable toxicity supporting its potential as a first-line therapy for HNSCC warranting further investigation in larger trials.Acknowledgements TiumBio Co., Ltd., Republic of Korea Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USATrial Registration Clinicaltrials.gov: NCT05204862 (Phase 1a) NCT05784688 (Phase 1b&2a)",
  "authors": [
    {
      "affiliations": [
        "Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea"
      ],
      "name": "Sung-Bae Kim"
    },
    {
      "affiliations": [
        "Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea"
      ],
      "name": "Bhumsuk Keam"
    },
    {
      "affiliations": [
        "Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea"
      ],
      "name": "Hye Ryun Kim"
    },
    {
      "affiliations": [
        "Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Republic of Korea"
      ],
      "name": "Jin Won Kim"
    },
    {
      "affiliations": [
        "Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea"
      ],
      "name": "Jin Hyoung Kang"
    },
    {
      "affiliations": [
        "St. Vincent’s Hospital, The Catholic University of Korea, Suwon-si, Republic of Korea"
      ],
      "name": "Ho-Jung An"
    },
    {
      "affiliations": [
        "Konkuk University Medical Center, Seoul, Republic of Korea"
      ],
      "name": "Ji-Hyun Park"
    },
    {
      "affiliations": [
        "TiumBio Co., Ltd., Seongnam-si, Gyeonggi-do, Republic of Korea"
      ],
      "name": "Hun-Taek Kim"
    },
    {
      "affiliations": [
        "Merck and Co., Inc, North Wales, PA, USA"
      ],
      "name": "Marya F Chaney"
    }
  ],
  "title": "549 Phase 2 trial of TU2218, TGFβ-RI and VEGF-R2 dual inhibitor in combination with pembrolizumab in patients with head and neck squamous cell carcinoma",
  "uid": "f316dc96-c1ff-5bf4-a034-e2964a0acb3e"
}