{
  "abstract": "Background Patients with metastatic colorectal cancer (mCRC) who are refractory to or intolerant of oxaliplatin and irinotecan have few effective treatment options. 1 2 Nelmastobart, a humanized monoclonal antibody targeting Butyrophilin 1A1 (BTN1A1), has shown preclinical and clinical antitumor activity with immunomodulatory effects.3 This study evaluated the safety and efficacy of Nelmastobart combined with capecitabine in patients with refractory mCRC.Methods This multicenter, open-label, phase 1b/2 study included a dose-escalation safety lead-in followed by dose expansion. In phase 1b, patients received Nelmastobart (400–800 mg) plus capecitabine (1,000–1,250 mg/m² twice daily, days 1–14 of a 21-day cycle) using a 3+3 design to determine the recommended phase 2 dose (RP2D). In phase 2, patients were treated at the RP2D until disease progression or unacceptable toxicity. Primary endpoints were dose-limiting toxicities (DLTs) and safety in phase 1b, and progression-free survival (PFS) in phase 2.Results Fifty-two patients were enrolled (median age, 58.5 years; range, 40–74). In phase 1b, 12 patients were treated across three dose levels; four DLTs occurred, all related to capecitabine. The RP2D was established as Nelmastobart 800 mg plus capecitabine 1,000 mg/m² twice daily. In phase 2, after a median follow-up of 6.4 months , the objective response rate (ORR) was 12.5% (95% CI, 4.2–26.8), and the disease control rate (DCR) was 72.5% (95% CI, 56.1–85.4). Median PFS was 4.2 months, while median overall survival (OS) was not reached at the time of analysis. The combination therapy was generally well tolerated. The most common adverse events of any grade were hand-foot syndrome, mucositis, and increased bilirubin. Grade ≥3 adverse events occurred in 5.8% of patients, including hand-foot syndrome, elevated AST, and peripheral neuropathy. No adverse events were attributed to Nelmastobart, and no treatment-related deaths occurred.Conclusions Nelmastobart combined with capecitabine demonstrated a manageable safety profile and encouraging antitumor activity in patients with refractory mCRC. These findings support further evaluation in larger, randomized trials, with an emphasis on biomarker-driven patient selection strategies.Acknowledgements This study was supported by grants and research funds from STCube Pharmaceutical.Trial Registration NCT05990543References Cervantes, Adam, Roselló, et al. Metastatic colorectal cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Onc. 2023;34(1):10–32.Prager, Taieb, Fakih, et al. Trifluridine-tipiracil and bevacizumab in refractory metastatic colorectal cancer. NEJM. 2023;388:1657–67.Kim, Lee, Yoo, et al. BTN1A1 is a novel immune checkpoint mutually exclusive to PD-L1. JITC. 2024;12:e008303. doi:10.1136/jitc-2023-008303Ethics Approval This study was approved by the IRB of Korea University Anam Hospital under the designation 2023AN0515.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": [
        "Korea University Anam Hospital, Seoul, Republic of Korea"
      ],
      "name": "Soohyeon Lee"
    }
  ],
  "title": "1341 A phase 1b/2 study of nelmastobart with capecitabine in patients with refractory mCRC",
  "uid": "652a2add-7e41-53fc-95d5-a1e084f34557"
}