{
  "abstract": "Background Osteosarcoma (OS) is an aggressive bone malignancy. Multidisciplinary treatment, including surgery, chemotherapy, and radiotherapy, has improved outcomes. Nevertheless, metastatic or recurrent cases still have poor prognosis, highlighting the need for novel therapies. TGF-β is a key cytokine driving OS progression by promoting immune suppression within the tumor microenvironment, tumor growth, and metastasis. 1–6 Therefore, targeting TGF-β-driven OS is a promising therapeutic strategy for patients with advanced or recurrent/refractory disease.Methods Eligible patients were adolescents (12 to <18 years) and adults (≥18 years) with histologically confirmed OS and ECOG PS 0–2. Adults received vactosertib monotherapy at 150, 200, or 300 mg BID, while adolescents were treated at 150 mg BID, with further dose exploration underway. The primary endpoint was safety, with secondary endpoints included antitumor activity. Exploratory endpoints included circulating TGF-β-related biomarkers.Results A total of 13 patients with recurrent, refractory, or progressive OS were enrolled. The median age was 30 years (range, 16-56), and patients had received a median of 7 prior lines of therapy (range, 1-11), indicative of a heavily pretreated population ( table 1).Among 11 evaluable patients, the overall response rate (ORR) was 36.4% (95% CI, 10.9–69.2), including 1 complete and 3 partial responses. Median progression-free survival (mPFS) was 1.9 months (95% CI, 1.2-not estimable), while median overall survival (mOS) reached 6.8 months (95% CI, 2.4-not estimable). Although early progression was common, all responders achieved objective and durable responses, with no evidence of disease flare.Responses were typically delayed, with a median time to response (TTR) of 9.6 months (range, 1.7–13.8); consequently, the observed median duration of response (DoR) was relatively short at 2.8 months (range, 2.0–2.9), reflecting the delayed onset of responses. Notably, two patients remained on therapy for over 12 months with sustained tumor regression, and two additional patients are still undergoing at data cutoff (September 3, 2025).Safety was assessed in all 13 patients. Treatment-emergent adverse events (TEAEs) related to the treatment occurred in 38.5% of patients, and were all manageable. Grade ≥3 treatment-related TEAEs included anemia (7.7%) and lipase increased (7.7%). In addition, one case of myelodysplastic syndrome occurred, which was considered unrelated to the treatment.Conclusions Vactosertib demonstrated a manageable safety profile and an encouraging antitumor activity, with an ORR of 36.4% with evidence of durable responses. These preliminary findings warrant further clinical investigation to validate the potential efficacy of vactosertib in osteosarcoma.Acknowledgements The authors thank the patients, their families, and caregivers for their participation and support.Trial Registration NCT05588648References Yang RS, et al. Tohoku J. Exp. Med. 1998;184:133–142.Xu S, et al. DNA and Cell Biology 2014;33(11):802–806.Pfeilschifter J, et al. Endocrinology 1987;121:212–218.Kloen P, et al. Int J Cancer 1994;58:440–445.Verrecchia F, Rédini F. Front Oncol. 2018;30(8):133.Caja F, Vannucci L. J Immunotoxicol. 2015;12:300–307.Ethics Approval The study was approved by Ethics Board of National Cancer Center (NCC2023-0182), Korea Institute of Radiological & Medical Sciences (KIRAMS 2023-04-001-001), Washington University of St. Louis and Sarcoma Oncology Research Center (SOC) (20226645).Abstract 1311 Table 1Baseline Characteristics[Abbreviation] ECOG PS; Eastern Cooperative Oncology Group Performance Status",
  "authors": [
    {
      "affiliations": [
        "National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea"
      ],
      "name": "Jun Ah Lee"
    },
    {
      "affiliations": [
        "UH Rainbow Babies and Children’s Hospital, Cleveland, OH, USA"
      ],
      "name": "Kristen VanHeyst"
    },
    {
      "affiliations": [
        "Korea Cancer Center Hospital, Seoul, Republic of Korea"
      ],
      "name": "Wan-Hyeong Cho"
    },
    {
      "affiliations": [
        "Washington University School of Medicine, St. Louis, MO, USA"
      ],
      "name": "Brian AVan Tine"
    },
    {
      "affiliations": [
        "Sarcoma Oncology Center, Santa Monica, CA, USA"
      ],
      "name": "Sant P Chawla"
    },
    {
      "affiliations": [
        "MedPacto, Inc., Seoul, Republic of Korea"
      ],
      "name": "Jaehyeon Kim"
    },
    {
      "affiliations": [
        "MedPacto, Inc., Seoul, Republic of Korea"
      ],
      "name": "Minkyu Heo"
    },
    {
      "affiliations": [
        "MedPacto Therapeutics, Gaithersburg, MD, USA"
      ],
      "name": "Saerom Kim"
    },
    {
      "affiliations": [
        "MedPacto, Inc., Seoul, Republic of Korea"
      ],
      "name": "Jungwon Woo"
    },
    {
      "affiliations": [
        "MedPacto, Inc., Seoul, Republic of Korea"
      ],
      "name": "Seong-Jin Kim"
    }
  ],
  "title": "1311 Targeting TGF-β RI signaling with the novel vactosertib: preliminary antitumor activity in a phase 1 study in patients with recurrent, refractory, and progressive osteosarcoma",
  "uid": "f294281f-88aa-5933-a034-8496adf1a342"
}