{
  "abstract": "Background\n\nImmune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted tyrosine kinase inhibitors (TKIs) have improved advanced renal cell carcinoma (RCC) outcomes, yet median progression-free survival (PFS) remains <2 years.Patients and methods\n\nThis randomised (1 : 1 : 1), open-label, phase II study (NCT05805501) evaluated tobemstomig [bispecific anti-programmed cell death protein 1 (PD-1)/lymphocyte-activation gene 3] plus axitinib (VEGF-TKI) and tobemstomig plus tiragolumab (anti-T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains) plus axitinib versus pembrolizumab (anti-PD-1) plus axitinib (control) in patients with untreated, locally advanced unresectable/metastatic clear-cell RCC with intermediate/poor International Metastatic Renal Cell Carcinoma Database Consortium risk. Following a protocol-specified interim futility analysis that led to study termination, the primary endpoint was amended from PFS and incidence/severity of adverse events (AEs) to the latter only. Efficacy was evaluated descriptively.Results\n\nIn the safety population (198 patients: tobemstomig-axitinib, n = 66; tobemstomig-tiragolumab-axitinib, n = 65; control, n = 67), grade 3-4 AEs occurred in 62.1%, 67.7% and 56.7% of patients in the respective arms and treatment-related serious AEs occurred in 22.7%, 29.2% and 13.4%. Confirmed overall response rates were 51.5%, 53.8% and 51.5%; median PFS was 12.4 [95% confidence interval (CI) 8.4-16.3], 12.5 (95% CI 7.3-17.2) and 12.5 months (95% CI 9.5 to not estimable).Conclusions\n\nTobemstomig-containing regimens were associated with increased toxicity and did not demonstrate meaningful efficacy improvement relative to control.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, USA. Electronic address: brian.rini@vumc.org.",
    "Barts Cancer Centre, Barts Health NHS Trust, Queen Mary University of London, London, UK.",
    "Department of Medical Oncology, Poznań University of Medical Sciences, Poznań, Poland.",
    "Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.",
    "Department of Neurology and Melanoma, Peking University Cancer Hospital and Institute, Beijung, China.",
    "Medical Oncology Department, Ramón y Cajal Health Research Institute (IRYCIS), CIBERONC, Alcalá University, University Hospital Ramon y Cajal, Madrid, Spain.",
    "Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.",
    "Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.",
    "Department of Oncology, Jagiellonian University Medical College, Cracow, Poland.",
    "Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain.",
    "Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, USA.",
    "Division of Hematology and Oncology, University of California at Irvine, Irvine, USA.",
    "Roche Products Limited, Welwyn Garden City, UK.",
    "Hoffmann-La Roche, Mississauga, Canada.",
    "Genentech, Inc. South San Francisco, San Francisco, USA.",
    "Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "B I Rini"
    },
    {
      "affs": [
        1
      ],
      "name": "T Powles"
    },
    {
      "affs": [
        2
      ],
      "name": "P Tomczak"
    },
    {
      "affs": [
        3
      ],
      "name": "S J Shin"
    },
    {
      "affs": [
        4
      ],
      "name": "J Guo"
    },
    {
      "affs": [
        5
      ],
      "name": "J Molina-Cerrillo"
    },
    {
      "affs": [
        6
      ],
      "name": "X Ren"
    },
    {
      "affs": [
        7
      ],
      "name": "J L Lee"
    },
    {
      "affs": [
        8
      ],
      "name": "P J Wysocki"
    },
    {
      "affs": [
        9
      ],
      "name": "J Puente"
    },
    {
      "affs": [
        10
      ],
      "name": "A Basu"
    },
    {
      "affs": [
        11
      ],
      "name": "N Mar"
    },
    {
      "affs": [
        12
      ],
      "name": "S Bernhard"
    },
    {
      "affs": [
        12
      ],
      "name": "O Khan"
    },
    {
      "affs": [
        12
      ],
      "name": "J Ha"
    },
    {
      "affs": [
        13
      ],
      "name": "L Colley"
    },
    {
      "affs": [
        14
      ],
      "name": "H Prizant"
    },
    {
      "affs": [
        15
      ],
      "name": "L Albiges"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5wph4522rhzxt.bib",
  "cited_by": 0,
  "doi": "10.1016/j.esmoop.2026.108587",
  "fulltext_url": "https://europepmc.org/articles/PMC13675702",
  "id": "5wph4522rhzxt",
  "issns": [
    "2059-7029"
  ],
  "landing_url": "https://europepmc.org/article/MED/42849355",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2740|Renal cell carcinoma treatment"
    ]
  ],
  "openalex": "W7220936520",
  "pdf_url": "https://europepmc.org/articles/PMC13675702?pdf=render",
  "pmcid": "PMC13675702",
  "pmid": "42849355",
  "published": "2026-10-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5wph4522rhzxt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:02Z",
      "native_id": "MED:42849355",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42849355"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Renal cell carcinoma treatment",
      "subfield": "general"
    }
  ],
  "title": "A randomised, open-label, phase II study of tobemstomig combinations in patients with previously untreated advanced clear-cell renal cell carcinoma.",
  "title_text": "A randomised, open-label, phase II study of tobemstomig combinations in patients with previously untreated advanced clear-cell renal cell carcinoma.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:02Z",
  "url": "https://research.draconitic.com/paper/5wph4522rhzxt",
  "venue": "ESMO open",
  "versions": []
}