Sistema de Salut de Catalunya
Institut Català de la Salut
[Gazzah A] Early Drug Development Department, Gustave Roussy, Villejuif, France. [Ricordel C] Department of Pulmonology, Centre Hospitalier Universitaire, Rennes, France. [Italiano A] Early Phase Trials Unit, Institut Bergonié, Bordeaux, France. Faculty of Medicine, University of Bordeaux, Bordeaux, France. [Cho BC] Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. [Calvo E] START Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Madrid, Spain. [Kim DW] Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. [Vieito Villar M] Medical Oncology Department, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2026-01-27T09:34:46Z
2026-01-27T09:34:46Z
2025-10
Antibody-drug conjugate; Carcinoembryonic antigen-related cell adhesion molecule 5; Non-small cell lung cancer
Conjugat anticòs-fàrmac; Molècula d'adhesió cel·lular relacionada amb l'antigen carcinoembrionari 5; Càncer de pulmó de cèl·lules no petites
Conjugado anticuerpo-fármaco; Molécula de adhesión celular relacionada con el antígeno carcinoembrionario 5; Cáncer de pulmón de células no pequeñas
Introduction Tusamitamab ravtansine is an antibody-drug conjugate targeting cells expressing carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) with a maytansinoid payload, DM4. This phase 1b dose-expansion study (NCT02187848) evaluated its safety, pharmacokinetics, and preliminary antitumor activity in patients with nonsquamous NSCLC (NSq NSCLC). Methods Patients aged above or equal to 18 years with advanced or metastatic NSq NSCLC, life expectancy more than or equal to 12 weeks, and high (≥2+ intensity in ≥50% of tumor cells) or moderate (≥2+ intensity in 1%–49% of tumor cells) CEACAM5 expression (assessed by immunohistochemistry) received intravenous tusamitamab ravtansine 100 mg/m2 every 2 weeks. Results A total of 64 patients with high and 28 with moderate CEACAM5 expression received a median of 8.0 (1–69) and 4.5 (1–38) treatment cycles, respectively. High expressors had 13 confirmed partial responses and 28 stable diseases (objective response rate, 20.3%; 95% confidence interval [CI]: 12.3%–31.7%, p < 0.0001); median duration of response was 6.7 months, and median time to progression was 3.7 months (95% CI: 2.7–5.1 mo). Moderate expressors had two confirmed partial responses (objective response rate, 7.1%; 95% CI: 2.0%–22.7%, p = 0.4117) and 15 stable diseases. Treatment-emergent adverse events (AEs) occurred in 78.3% of patients (72/92), 37.0% (34/92) of patients required dose modifications, and 5.4% (5/92) discontinued treatment. The most common treatment-emergent AEs included asthenia (37.0%), keratitis (29.3%), and dyspnea (23.9%). Corneal AEs occurred in 38.0% (35/92), typically grade 1/2, reversible, and manageable by dose modifications. Conclusions Tusamitamab ravtansine demonstrated a favorable safety profile, objective responses, and antitumor activity in patients with high CEACAM5-expressing NSq NSCLC.
This work was supported by Sanofi.
Article
Published version
English
Posologia; Immunoglobulines - Ús terapèutic; Medicaments antineoplàstics - Ús terapèutic; Molècules d'adhesió cel·lular; Immunoglobulines - Farmacocinètica; Pulmons - Càncer - Tractament; CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Serum Globulins::Immunoglobulins::Antibodies::Immunoconjugates; Other subheadings::Other subheadings::Other subheadings::/pharmacokinetics; DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung; Other subheadings::Other subheadings::Other subheadings::/drug therapy; PHENOMENA AND PROCESSES::Physiological Phenomena::Pharmacological and Toxicological Phenomena::Pharmacological Phenomena::Dose-Response Relationship, Drug; CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Cell Adhesion Molecules::Carcinoembryonic Antigen; COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::globulinas séricas::inmunoglobulinas::anticuerpos::inmunoconjugados; Otros calificadores::Otros calificadores::Otros calificadores::/farmacocinética; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; FENÓMENOS Y PROCESOS::fenómenos fisiológicos::fenómenos farmacológicos y toxicológicos::fenómenos farmacológicos::relación dosis-respuesta de medicamentos; COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::glicoproteínas::glicoproteínas de membranas::moléculas de adhesión celular::antígeno carcinoembrionario
Elsevier
JTO Clinical and Research Reports;6(10)
https://doi.org/10.1016/j.jtocrr.2025.100844
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
