{
  "abstract": "Background Metastatic colorectal cancer (mCRC) has poor prognosis after progression on or intolerance to oxaliplatin- and irinotecan-based chemotherapy. Although trifluridine/tipiracil plus bevacizumab improves survival, durable responses are uncommon, underscoring the need for new strategies. BTN1A1, a newly identified immune checkpoint, is implicated in immune evasion. 1 Nelmastobart, a first-in-class anti-BTN1A1 antibody, restored T-cell proliferation and antitumor activity in preclinical models. Clinical activity was also observed in other studies (NCT05231746 and NCT0599054), supporting its potential. Based on this rationale, the multicenter Phase 1b/2 trial (NCT06873763) was designed to evaluate Nelmastobart with trifluridine/tipiracil and bevacizumab in refractory mCRC. This abstract reports Phase 1b safety run-in results focusing on safety, pharmacokinetics (PK), and preliminary efficacy.Methods This Phase 1b safety run-in of the open-label Phase 1b/2 trial evaluates Nelmastobart with trifluridine/tipiracil and bevacizumab in patients with metastatic or recurrent CRC refractory or intolerant to oxaliplatin- and irinotecan-based therapy. Phase 1b applies a 6+6 design to evaluate dose-limiting toxicities (DLTs) and establish the recommended Phase 2 dose (RP2D). Treatment is administered in 28-day cycles: Nelmastobart and bevacizumab on Days 1 and 15, and trifluridine/tipiracil on Days 1–5 and 8–12. Phase 2 will enroll BTN1A1-positive patients (TPS ≥50% by IHC) to assess efficacy, with progression-free survival as the primary endpoint and overall survival, objective response rate, and safety as secondary endpoints. Planned enrollment is 61 patients over ~30 months.Results From June to August 2025, six patients (mean age 63.5 years; 2 male, 4 female) were enrolled. BTN1A1 expression was confirmed in all tumors: one low (TPS 20, H-score 20) and five high (TPS ≥50). H-scores ranged from 20 to 300 and correlated with TPS (r = 0.84). No DLTs occurred. The most common adverse events were leukopenia (83.3%), neutropenia (66.7%), nausea (66.7%), and anemia (50.0%), consistent with chemotherapy; none attributed to Nelmastobart. At 2 months, four patients had stable disease and two partial responses, with tumor reductions of 31% and 52.1%.Conclusions Nelmastobart plus trifluridine/tipiracil and bevacizumab was well tolerated, with no drug-related toxicities. BTN1A1 expression (TPS ≥50) was observed in >80% of tumors, supporting biomarker-driven selection. PK was consistent with prior data. Two partial responses and four decreasing stable diseases demonstrated strong antitumor activity. Along with prior efficacy, these findings support continued development. The ongoing Phase 2 expansion will further validate BTN1A1-guided patient selection and clinical utility.Trial Registration The ClinicalTrials.gov ID for the phase 1b/II clinical trial is NCTNCT06873763.Reference Kim Y, Lee S, Park AH, Wu C, Hong B, Jung H, et al. BTN1A1 is a novel immune checkpoint mutually exclusive to PD-L1. Journal for ImmunoTherapy of Cancer. 2024;12:e008303.Ethics Approval The Protocol and informed consent form (ICF) were submitted to and approved by the duly constituted Institutional Review Board (IRB), Korea University Anam Hospital IRB or Independent Ethics Committee (IEC) for each center prior to initiation of the study. The study was conducted in accordance with the Declaration of Helsinki and with all applicable laws and regulations of the locale and country where the study was conducted, and in compliance with Good Clinical Practice Guidelines. The number of the IRB approval is 2025AN0204.Consent In this study, we don’t contain sensitive and identifiable information about patients.",
  "authors": [
    {
      "affiliations": [
        "Korea University Anam Hospital, Seoul, Republic of Korea"
      ],
      "name": "Soohyeon Lee"
    },
    {
      "affiliations": [
        "Sungkyunkwan University School of Medicine, Seoul, Republic of Korea"
      ],
      "name": "Yoon-La Choi"
    },
    {
      "affiliations": [
        "Sungkyunkwan University School of Medicine, Seoul, Republic of Korea"
      ],
      "name": "Bogyeong Han"
    },
    {
      "affiliations": [
        "STCube, Inc, Seoul, Republic of Korea"
      ],
      "name": "Hyunjin Jung"
    },
    {
      "affiliations": [
        "Stcube Pharmaceuticals Inc, Rockville, MD, USA"
      ],
      "name": "Stephen S Yoo"
    }
  ],
  "title": "1313 Nelmastobart combination shows excellent tolerability and early antitumor activity in refractory mCRC",
  "uid": "d67411cd-e381-5162-96c6-19b1b5bfb938"
}