Practical management of adverse events in patients receiving tarlatamab, a delta-like ligand 3-targeted bispecific T-cell engager immunotherapy, for previously treated small cell lung cancer.

Stéphane Champiat, Ali Hamidi, Philip E Lammers, Sally C M Lau, Jeffrey M Clarke, Jennifer W Carlisle, Jean Bustamante Alvarez, Kelly G Paulson, Horst-Dieter Hummel, Jacob M Sands, Noura J Choudhury, Sujoy Mukherjee, Shuang Huang, Taofeek K Owonikoko, Hossein Borghaei, Shirish M Gadgeel, David P Carbone, Hiroki Izumi, Alejandro Navarro

Journal: Cancer 2025;131(3):e35738

PMID: 39876075

Abstract

Tarlatamab is a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 (DLL3) and the cluster of differentiation 3 (CD3) molecule. In the phase 2 DeLLphi-301 trial of tarlatamab for patients with previously treated small cell lung cancer, tarlatamab 10 mg every 2 weeks achieved durable responses and encouraging survival outcomes. Analyses of updated safety data from the DeLLphi-301 trial demonstrated that the most common treatment-emergent adverse events were cytokine release syndrome (53%), pyrexia (38%), decreased appetite (36%), dysgeusia (32%), and an emia (30%). Cytokine release syndrome was mostly grade 1 or 2 in severity, occurred primarily after the first or second tarlatamab dose, and was managed with supportive care, which included the administration of antipyretics (e.g., acetaminophen), intravenous hydration, and/or glucocorticoids. Other treatment-emergent adverse effects of interest included neutropenia (16%) and immune effector cell-associated neurotoxicity syndrome and associated neurologic events (10%). Given that tarlatamab is the first T-cell engager approved for the treatment of small cell lung cancer, raising awareness with regard to the monitoring and management of tarlatamab-associated adverse events is essential. Here, the authors describe the timing, occurrence, and duration of these adverse events and review the management and risk-mitigation strategies used by clinical investigators during the DeLLphi-301 trial.

© 2025 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.

Address: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.; Département d'Innovation Thérapeutique et des Essais Précoces, Gustave Roussy, Villejuif, France.; Translational Oncology/Early Clinical Trial Unit, Bavarian Cancer Research Center, National Center for Tumor Diseases, Comprehensive Cancer Center Mainfranken and University Hospital Wurzburg, Wurzburg, Germany.; Department of Medical Oncology, Providence-Swedish Cancer Institute, Seattle, Washington, USA.; Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.; New York Cancer and Blood Specialists, New York, New York, USA.; The Ohio State Health Network, The Ohio State University, Columbus, Ohio, USA.; Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Duke Cancer Institute, Duke University, Durham, North Carolina, USA.; Henry Ford Cancer Institute, Detroit, Michigan, USA.; Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.; Department of Medicine, University of Barcelona, Hospital Clinic and IDIBAPS, Barcelona, Spain.; Department of Medical Oncology, New York University Langone Health Perlmutter Cancer Center and Grossman School of Medicine, New York, New York, USA.; Baptist Cancer Center, Memphis, Tennessee, USA.; Amgen Inc., Thousand Oaks, California, USA.; University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical Center, Baltimore, Maryland, USA.
Bant logo

© Copyright 2026, Nutrition Evidence

NED wishes to thank the following organisations for their support:

We use cookies to improve your experience and analyze site traffic with Google Analytics. By continuing to use our site, you agree to our use of cookies. Learn more.