{
  "abstract": "Successful cancer immunotherapy requires not only tumor cell killing but also the activation of innate and adaptive immune responses. The inhibitor of apoptosis (IAP) proteins cIAP1, cIAP2 and XIAP act as key suppressors of RIPK1-driven immunogenic cell death, thereby enabling tumor immune evasion and limiting the effectiveness of immune checkpoint blockade (ICB). ASTX660 (tolinapant) is a non-peptidomimetic antagonist with a balanced activity against all clinically relevant IAPs, designed to lower the TNF cytotoxicity threshold and sensitize tumors to T cell-mediated killing. Here, we present results from the phase I ASTEROID trial (NCT05082259), evaluating ASTX660 in combination with pembrolizumab in patients with advanced solid tumors. Primary endpoints were recommended phase 2 dose (RP2D) and safety, while secondary endpoints were anti-tumor activity and pharmacokinetics. The combination was well tolerated and demonstrated early evidence of efficacy. RP2D was ASTX660 150 mg (7-days-on/14-days-off) with pembrolizumab. Overall response rate was 33%, including responses in ER⁺ breast cancers typically resistant to ICB. Integrated translational analyses reveal that response is associated with a TNF/IFN-enriched inflammatory tumor microenvironment, increased tumor antigenicity and enhanced TCR clonal diversity, whereas resistance correlates with a CCR4/6/7/8-driven TAM/Treg-dominant niche. Together, these results provide clinical proof-of-concept that dual IAP and PD-1 blockade sensitize tumors, while identifying candidate biomarkers to guide patient stratification in future studies.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 60,
  "authors": [
    {
      "name": "Crescens Tiu",
      "orcid": "0000-0002-0515-6130"
    },
    {
      "name": "Wing Yau",
      "orcid": "0000-0003-3550-4420"
    },
    {
      "name": "Tencho Tenev"
    },
    {
      "name": "Daniel Lionarons"
    },
    {
      "name": "Ching Leung"
    },
    {
      "name": "Victoria Sanchez-Perez"
    },
    {
      "name": "Giovanni Codacci-Pisanelli"
    },
    {
      "name": "Xiaoran Lai",
      "orcid": "0000-0002-7364-3993"
    },
    {
      "name": "Anna Zachariou"
    },
    {
      "name": "Aasia Hussain"
    },
    {
      "name": "Toby Prout"
    },
    {
      "name": "Mona Parmar",
      "orcid": "0000-0001-7818-4100"
    },
    {
      "name": "Bindu Baikady"
    },
    {
      "name": "Maria Goicoechea"
    },
    {
      "name": "Scott Layzell"
    },
    {
      "name": "Naomi Guppy",
      "orcid": "0000-0003-1004-3605"
    },
    {
      "name": "Ioannis Roxanis"
    },
    {
      "name": "Thomas Lund",
      "orcid": "0000-0001-5400-7230"
    },
    {
      "name": "Diego Carlos Dos Reis"
    },
    {
      "name": "Camila Pereira Almeida"
    },
    {
      "name": "Tatiany Luiza Silveira"
    },
    {
      "name": "Ana Ferreira"
    },
    {
      "name": "Bora Gurel",
      "orcid": "0000-0002-5018-8078"
    },
    {
      "name": "Claudia Bertan"
    },
    {
      "name": "Mateus Crespo",
      "orcid": "0000-0003-4043-8296"
    },
    {
      "name": "Penny Flohr"
    },
    {
      "name": "Ann-Marie Baker",
      "orcid": "0000-0001-8905-9137"
    },
    {
      "name": "Trevor Graham",
      "orcid": "0000-0001-9582-1597"
    },
    {
      "name": "Luis Zapata",
      "orcid": "0000-0002-1386-2019"
    },
    {
      "name": "Claudio Salas"
    },
    {
      "name": "Soham Mandal"
    },
    {
      "name": "Alan Dunlop"
    },
    {
      "name": "Martin Sims",
      "orcid": "0009-0001-8684-6095"
    },
    {
      "name": "George Ward",
      "orcid": "0000-0001-9960-3896"
    },
    {
      "name": "Tomoko Smyth",
      "orcid": "0009-0004-5796-4377"
    },
    {
      "name": "Simone Jueliger"
    },
    {
      "name": "Matthew Davis",
      "orcid": "0000-0002-9909-3651"
    },
    {
      "name": "Ilya Potapov"
    },
    {
      "name": "Aram Oganesian"
    },
    {
      "name": "Danna Chan"
    },
    {
      "name": "Mattias Leino",
      "orcid": "0000-0002-7533-043X"
    },
    {
      "name": "Subham Basu"
    },
    {
      "name": "Andre Samson",
      "orcid": "0000-0002-0637-2716"
    },
    {
      "name": "James M. Murphy",
      "orcid": "0000-0003-0195-3949"
    },
    {
      "name": "Nina Tunariu"
    },
    {
      "name": "Edward W. Johnston"
    },
    {
      "name": "Alistair Ring"
    },
    {
      "name": "Nick Turner",
      "orcid": "0000-0001-8937-0873"
    },
    {
      "name": "Andrew N. J. Tutt",
      "orcid": "0000-0001-8715-2901"
    },
    {
      "name": "Amanda Swain",
      "orcid": "0000-0001-8666-1608"
    },
    {
      "name": "Anna Minchom",
      "orcid": "0000-0002-9339-7101"
    },
    {
      "name": "Adam Sharp",
      "orcid": "0000-0002-3740-1612"
    },
    {
      "name": "Alec Paschalis"
    },
    {
      "name": "Udai Banerji",
      "orcid": "0000-0003-1503-3123"
    },
    {
      "name": "Johann de Bono",
      "orcid": "0000-0002-2034-595X"
    },
    {
      "name": "Bristi Basu"
    },
    {
      "name": "Christina Yap",
      "orcid": "0000-0002-6715-2514"
    },
    {
      "name": "Syed Haider",
      "orcid": "0000-0001-6685-5480"
    },
    {
      "name": "Juanita Lopez",
      "orcid": "0000-0001-8321-4212"
    },
    {
      "name": "Pascal Meier",
      "orcid": "0000-0003-2760-6523"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bs50p01g6yy8g.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-77552-7",
  "fulltext_url": "https://europepmc.org/articles/PMC13720124",
  "id": "bs50p01g6yy8g",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://www.nature.com/articles/s41467-026-77552-7",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
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      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
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  "pdf_url": "https://www.nature.com/articles/s41467-026-77552-7.pdf",
  "pmcid": "PMC13720124",
  "pmid": "42957672",
  "published": "2026-09-30",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/bs50p01g6yy8g.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:38Z",
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
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  ],
  "title": "IAP antagonist tolinapant (ASTX660) in combination with pembrolizumab in advanced solid tumors: a phase I trial",
  "title_text": "IAP antagonist tolinapant (ASTX660) in combination with pembrolizumab in advanced solid tumors: a phase I trial",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:04Z",
  "url": "https://research.draconitic.com/paper/bs50p01g6yy8g",
  "venue": "Nature Communications",
  "versions": []
}