评估图沙米妥单抗拉坦赛辛在癌胚抗原相关细胞黏附分子5高表达或中度表达的非鳞状非小细胞肺癌患者中的安全性、药代动力学及抗肿瘤活性。

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.

作者信息

Gazzah Anas, Ricordel Charles, Italiano Antoine, Cho Byoung Chul, Calvo Emiliano, Kim Dong-Wan, Helissey Carole, Kim Jin-Soo, Villar Maria Vieito, Ghiringhelli Francois, Moreno Victor, Cousin Sophie, Paz-Ares Luis, Fagniez Nathalie, Chadjaa Mustapha, Bauchet Anne-Laure, Soufflet Christine, Masson Nina, Barlesi Fabrice

机构信息

Early Drug Development Department, Gustave Roussy, Villejuif, France.

Department of Pulmonology, Centre Hospitalier Universitaire, Université de Rennes 1, Rennes, France.

出版信息

JTO Clin Res Rep. 2025 May 15;6(10):100844. doi: 10.1016/j.jtocrr.2025.100844. eCollection 2025 Oct.

DOI:10.1016/j.jtocrr.2025.100844

PMID:41031047

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12478256/

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/m 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%, < 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%, = 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.

摘要

引言

图萨米他单抗拉伐他汀是一种抗体药物偶联物，靶向表达癌胚抗原相关细胞粘附分子5（CEACAM5）的细胞，其负载的美登素类似物为DM4。这项1b期剂量扩展研究（NCT02187848）评估了其在非鳞状非小细胞肺癌（NSq NSCLC）患者中的安全性、药代动力学和初步抗肿瘤活性。

方法

年龄大于或等于18岁、患有晚期或转移性NSq NSCLC、预期寿命大于或等于12周且CEACAM5表达高（≥50%的肿瘤细胞中强度≥2+）或中度（1%-49%的肿瘤细胞中强度≥2+）（通过免疫组织化学评估）的患者每2周静脉注射100 mg/m²的图萨米他单抗拉伐他汀。

结果

共有64例CEACAM5高表达患者和28例中度表达患者分别接受了中位数为8.0（1-69）和4.5（1-38）个治疗周期的治疗。高表达患者有13例确认的部分缓解和28例病情稳定（客观缓解率为20.3%；95%置信区间[CI]：12.3%-31.7%，P<0.0001）；中位缓解持续时间为6.7个月，中位疾病进展时间为3.7个月（95%CI：2.7-5.1个月）。中度表达患者有2例确认的部分缓解（客观缓解率为7.1%；95%CI：2.0%-22.7%，P=0.4117）和15例病情稳定。78.3%（72/92）的患者发生了治疗中出现的不良事件（AE），37.0%（34/92）的患者需要调整剂量，5.4%（5/92）的患者停止治疗。最常见的治疗中出现的AE包括乏力（37.0%）、角膜炎（29.3%）和呼吸困难（23.9%）。38.0%（35/92）的患者出现角膜AE，通常为1/2级，可逆，可通过调整剂量控制。