{
  "abstract": "Background T-cell immunoglobulin and mucin-domain containing 3 (TIM-3) is an inhibitory receptor linked to decreased antitumor activity of immune cells. S095018 is a human anti-TIM-3 IgG2 antibody that blocks the binding of phosphatidyl serine to TIM-3. Sym021 is a humanized IgG1 antibody that inhibits the binding of programmed cell death protein-1 (PD-1) to its ligands programmed death-ligand 1 (PD-L1) and PD-L2.Methods S095018 in combination with Sym021 was tested in patients with advanced/metastatic biliary tract cancers (BTC) whose disease progressed under treatment with at least 1 line of systemic therapy and who had not received prior treatment with PD-(L)1 inhibitors ( NCT04641871). Patients received 3 mg/kg of Sym021 and 10 mg/kg of S095018 once every 2 weeks. Primary endpoints included overall response rate and incidence/severity of adverse events. Key secondary endpoints included pharmacokinetics, immunogenicity assessment, progression-free survival (PFS) and overall survival (OS).Results 35 patients with stage IV BTC received S095018 in combination with Sym021. A partial response was achieved in 2 patients (5.7%) and stable disease in 11 patients (31.4%) for a disease control rate of 37%; 4 patients were not evaluable for response. Median PFS and OS were 1.9 months (90% CI 1.8 to 3.7) and 13.4 months (90% CI 8.2 to 27.1), respectively. The most common treatment-emergent adverse events of any grade included fatigue, pruritus, infusion-related reaction, and increases in amylase (8.6% each). Exploratory biomarker analyses in paired tumor biopsies showed an increase in intratumoral CD8 T-cell density and an upregulation of gene signatures related to interferon-γ signaling, antigen presentation, and T-cell activation with treatment without, however, clear association with efficacy endpoints.Conclusions Dual PD-1/TIM-3 inhibition was tolerable but exhibited modest antitumor activity in patients with advanced/metastatic recurrent BTC who had not received prior anti-PD-(L)1 treatment.",
  "authors": [
    {
      "affiliations": [
        "Centre Georges-Francois Leclerc, Dijon, Bourgogne-Franche-Comté, France"
      ],
      "name": "Francois Ghiringhelli"
    },
    {
      "affiliations": [
        "H Lee Moffitt Cancer Center and Research Institute Department of Gastrointestinal Oncology, Tampa, Florida, USA"
      ],
      "name": "Richard Kim"
    },
    {
      "affiliations": [
        "Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain"
      ],
      "name": "Teresa Macarulla"
    },
    {
      "affiliations": [
        "Start Madrid- CIOCC, Centro Integral Oncologico Clara Campal, Madrid, Spain"
      ],
      "name": "Irene Moreno"
    },
    {
      "affiliations": [
        "Division of Medical Oncology and Hematology, University Health Network, Princess Margaret Cancer Centre, Toronto, Canada"
      ],
      "name": "Albiruni Abdul Razak"
    },
    {
      "affiliations": [
        "University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Jordi Rodon Ahnert"
    },
    {
      "affiliations": [
        "Department of Medicine, Section of Hematology/Oncology, The University of Chicago Medicine Comprehensive Cancer Center, Chicago, Illinois, USA"
      ],
      "name": "Chih-Yi Liao"
    },
    {
      "affiliations": [
        "Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"
      ],
      "name": "Sarah Lindsey Davis"
    },
    {
      "affiliations": [
        "UH Seidman Cancer Center, Cleveland, Ohio, USA"
      ],
      "name": "Amit Mahipal"
    },
    {
      "affiliations": [
        "Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, USA"
      ],
      "name": "Thomas Marron"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Institut de Cancérologie de l’Ouest, Saint Herblain, France"
      ],
      "name": "Judith Raimbourg"
    },
    {
      "affiliations": [
        "Servier, Gif-sur-Yvette, France"
      ],
      "name": "Hélène Kaplon"
    },
    {
      "affiliations": [
        "Servier, Gif-sur-Yvette, France"
      ],
      "name": "Julia Geronimi"
    },
    {
      "affiliations": [
        "Servier, Gif-sur-Yvette, France"
      ],
      "name": "Najah Harouki"
    },
    {
      "affiliations": [
        "Servier, Gif-sur-Yvette, France"
      ],
      "name": "Christelle Rodrigues"
    },
    {
      "affiliations": [
        "Servier, Gif-sur-Yvette, France"
      ],
      "name": "Pauline Darcel"
    },
    {
      "affiliations": [
        "Symphogen A/S, Ballerup, Denmark"
      ],
      "name": "Janus Schou Jakobsen"
    },
    {
      "affiliations": [
        "Symphogen A/S, Ballerup, Denmark"
      ],
      "name": "Niels Skartved"
    },
    {
      "affiliations": [
        "Symphogen A/S, Ballerup, Denmark"
      ],
      "name": "Rikke Hald"
    },
    {
      "affiliations": [
        "Symphogen A/S, Ballerup, Denmark"
      ],
      "name": "Daleen Lopez-Ravnborg"
    },
    {
      "affiliations": [
        "Servier, Boston, Massachusetts, USA"
      ],
      "name": "Peng He"
    },
    {
      "affiliations": [
        "Servier, Boston, Massachusetts, USA"
      ],
      "name": "Xenophon Ianopoulos"
    },
    {
      "affiliations": [
        "Servier, Boston, Massachusetts, USA"
      ],
      "name": "Vasileios Askoxylakis"
    },
    {
      "affiliations": [
        "Developmental Therapeutics, START Midwest, Grand Rapids, Michigan, USA"
      ],
      "name": "Nehal Lakhani"
    }
  ],
  "title": "Phase Ib multicenter study of anti-TIM-3 (S095018/Sym023) in combination with anti-PD-1 (Sym021) in patients with advanced/metastatic recurrent biliary tract cancer",
  "uid": "860a4f4f-43e6-5ed3-b2d7-fc40cd6b637d"
}