Evaluation of the Safety, Pharmacokinetics, and Antitumor Activity of Tusamitamab Ravtansine in Patients With Nonsquamous NSCLC With High or Moderate Expression of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5

Abstract

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. Copyright (c) 2025 by the International Association for the Study of Lung Cancer. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).