System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Review Ahead of print

PubMed: 42962497 DOI: 10.1016/j.ctrv.2026.103201

T-cell engagers in small-cell lung cancer: current evidence and future directions - a position statement from the ETOP IBCSG Partners Foundation Workshop.

Cancer Treat Rev 151:103201

Authors: May-Lucie Meyer, Solange Peters, Myung-Ju Ahn, Isabelle Beuchat, Hossein Borghaei, Lauren A Byers, Federico Cappuzzo, Noura J Choudhury, Johann de Bono, Enriqueta Felip, Carl M Gay, Ramaswamy Govindan, Felix John, Stephen V Liu, Margarita Majem, Markus G Manz, Arancha Manzano, Tony Mok, Giannis Mountzios, Jarushka Naidoo, Tom Newsom-Davis, Taofeek K Owonikoko, Luis Paz-Ares, Maurice Pérol, Egle Ramelyte, Martin Reck, Jordi Remon, Jacob Sands, Martin Schuler, Triparna Sen, Daniel S W Tan, Andreas Viardot, Martin Wermke, James C H Yang, Rolf A Stahel

Affiliations

  • Oncology Department, Centre Hospitalier Universitaire Vaudois (CHUV), Rue de Bugnon 21, CH-1011 Lausanne, Switzerland.
  • Oncology Department, Centre Hospitalier Universitaire Vaudois (CHUV), Rue de Bugnon 21, CH-1011 Lausanne, Switzerland.
  • Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul, South Korea.
  • Department of Neuroscience, Neurology Service, Lausanne University Hospital, Unicentre, CH-1015 Lausanne, Switzerland.
  • Hematology and Oncology Department, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA.
  • Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Holcombe Boulevard, Houston, TX 77030-4009, USA.
  • Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
  • Department of Medicine, University of Chicago, 5801 South Ellis Avenue, Chicago, IL 60637, USA.
  • The Institute of Cancer Research, The Royal Marsden Hospital, 203 Fulham Road, London SW3 6JJ, UK.
  • Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Carrer de Natzaret 115-117, 08035 Barcelona, Spain.
  • Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Holcombe Boulevard, Houston, TX 77030-4009, USA.
  • Alvin J. Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
  • Department I of Internal Medicine, Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf, Lung Cancer Group Cologne, University of Cologne, Albertus-Magnus-Platz, 50923 Cologne, Germany.
  • Lombardi Comprehensive Cancer Center, Georgetown University, 3800 Reservoir Road NW, Washington, DC 20057, USA.
  • Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Carrer de Sant Quintí 89, 08041 Barcelona, Spain.
  • Department of Medical Oncology and Hematology, Comprehensive Cancer Center Zurich, University of Zurich, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.
  • Advanced and Cellular Therapy in Patient Value Area (ACTIVA), Department of Medical Oncology, Hospital Universitario 12 de Octubre, Avda de Córdoba, 28041 Madrid, Spain.
  • State Key Laboratory of South China, Chinese University of Hong Kong, Sha Tin, New Territories, Hong Kong Special Administrative Region of China.
  • Fourth Department of Medical Oncology and Clinical Trials Unit, Henry Dunant Hospital Center, 107 Mesogeion Avenue, 115 26 Athens, Greece.
  • Department of Medical Oncology, Beaumont RCSI Cancer Centre, Beaumont Road, Dublin 9, Ireland.
  • Department of Oncology, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK.
  • University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, 22 South Greene Street, Baltimore, MD 21201, USA.
  • Advanced and Cellular Therapy in Patient Value Area (ACTIVA), Department of Medical Oncology, Hospital Universitario 12 de Octubre, Avda de Córdoba, 28041 Madrid, Spain.
  • Department of Medical Oncology, Centre Léon Bérard, 28 Rue Laennec, 69008 Lyon, France.
  • Department of Dermatology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland; Faculty of Medicine, University of Zurich, Pestalozzistrasse 3, 8032 Zurich, Switzerland.
  • Department of Thoracic Oncology, LungenClinic, Airway Research Center North, German Center for Lung Research, Wöhrendamm 80, 22927 Grosshansdorf, Germany.
  • Department of Cancer Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94800 Villejuif, France.
  • Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
  • Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany; National Center for Tumor Diseases (NCT), NCT West, Hufelandstrasse 55, 45147 Essen, Germany.
  • Division of Medical Oncology, Arthur G. James Comprehensive Cancer Center, Ohio State University, 460 West 10th Avenue, Columbus, OH 43210, USA.
  • Division of Medical Oncology, National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore 168583, Singapore.
  • Department of Internal Medicine III, University Hospital, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
  • NCT/UCC Early Clinical Trial Unit, Technical University Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
  • School of Medicine, National Taiwan University Hospital, 7 Zhongshan South Road, Zhongzheng District, Taipei City, Taiwan; Department of Oncology, National Taiwan University Cancer Center, 57 Keelung Road, Da'an District, Taipei City, Taiwan.
  • Coordinating Center, ETOP IBCSG Partners Foundation, Effingerstrasse 33, 3008 Bern, Switzerland.

Abstract

T-cell engagers (TCEs) are a novel class of immunotherapeutic molecules that enhance immune responses to cancer by directing T cells to target tumour cells. Tumour-associated antigens have been identified for several solid malignancies, including delta-like ligand 3 (DLL3) for small-cell lung cancer (SCLC). Several DLL3-targeted TCEs are being developed for the treatment of SCLC, including tarlatamab, gocatamig and obrixtamig. Tarlatamab is approved by the United States Food and Drug Administration and represents a new standard of care in patients with pretreated SCLC. As experience with TCEs in SCLC increases, consensuses on optimal clinical settings and patient management are evolving. Rapid identification and effective management of potentially life-threatening immune-related side-effects, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), are essential for successful treatment with TCEs. Here we briefly review the key studies of TCEs in development for solid tumours before providing a comprehensive discussion on the clinical management of TCE therapy in patients with SCLC. We consider issues related to clinical settings, patient evaluation and management of toxicities, with a particular focus on identification and treatment of CRS and ICANS, drawing on experience from other oncology settings. TCEs represent a transformative treatment option for SCLC, offering new hope for a disease traditionally associated with poor therapeutic outcomes. TCEs also, however, bring new challenges, including the effective management of immune-related side-effects and the logistical demands of treatment. Safe implementation will depend on robust infrastructure, multidisciplinary collaboration, and patient and caregiver education.

MeSH

Cells, Lung, Neoplasms, Lung Neoplasms, Small Cell Lung Carcinoma, United States Food And Drug Administration, Foundations, Therapeutics, T-Lymphocytes