2. Academic Validation
  3. 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

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

  • J Immunother Cancer. 2026 Mar 13;14(3):e012344. doi: 10.1136/jitc-2025-012344.
Francois Ghiringhelli 1,  Richard Kim 2,  Teresa Macarulla 3,  Irene Moreno 4,  Albiruni Abdul Razak 5,  Jordi Rodon Ahnert 6,  Chih-Yi Liao 7,  Sarah Lindsey Davis 8,  Amit Mahipal 9,  Thomas Marron 10,  Judith Raimbourg 11,  Hélène Kaplon 12,  Julia Geronimi 12,  Najah Harouki 12,  Christelle Rodrigues 12,  Pauline Darcel 12,  Janus Schou Jakobsen 13,  Niels Skartved 13,  Rikke Hald 13,  Daleen Lopez-Ravnborg 13,  Peng He 14,  Xenophon Ianopoulos 14,  Vasileios Askoxylakis 14,  Nehal Lakhani 15
Affiliations

Affiliations

  • 1 Centre Georges-Francois Leclerc, Dijon, Bourgogne-Franche-Comté, France [email protected].
  • 2 H Lee Moffitt Cancer Center and Research Institute Department of Gastrointestinal Oncology, Tampa, Florida, USA.
  • 3 Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
  • 4 Start Madrid- CIOCC, Centro Integral Oncologico Clara Campal, Madrid, Spain.
  • 5 Division of Medical Oncology and Hematology, University Health Network, Princess Margaret Cancer Centre, Toronto, Canada.
  • 6 University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  • 7 Department of Medicine, Section of Hematology/Oncology, The University of Chicago Medicine Comprehensive Cancer Center, Chicago, Illinois, USA.
  • 8 Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
  • 9 UH Seidman Cancer Center, Cleveland, Ohio, USA.
  • 10 Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • 11 Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Saint Herblain, France.
  • 12 Servier, Gif-sur-Yvette, France.
  • 13 Symphogen A/S, Ballerup, Denmark.
  • 14 Servier, Boston, Massachusetts, USA.
  • 15 Developmental Therapeutics, START Midwest, Grand Rapids, Michigan, USA.
PMID: 41825935 DOI: 10.1136/jitc-2025-012344
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.

Keywords

Biliary Tract Cancer; Immune Checkpoint Inhibitor; Immunotherapy.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P992454
    TIM3 Inhibitor