Tusamitamab Ravtansine在癌胚抗原相关细胞粘附分子高或中度表达的非鳞状NSCLC患者中的安全性、药代动力学和抗肿瘤活性评价

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports Pub Date : 2025-05-15 DOI:10.1016/j.jtocrr.2025.100844

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

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引用次数: 0

摘要

tusamitamab ravtansine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，具有美坦素类有效载荷DM4。这项1b期剂量扩展研究（NCT02187848）评估了其在非鳞状NSCLC （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≥18岁的晚期或转移性NSq NSCLC患者，预期寿命≥12周，CEACAM5高表达（≥50%肿瘤细胞≥2+强度）或中等表达（≥1%-49%肿瘤细胞≥2+强度）（免疫组化评估），每2周静脉注射tusamitamab ravtansine 100mg /m2。结果CEACAM5高表达患者64例，中等表达患者28例，治疗周期中位数分别为8.0（1-69）和4.5（1-38）。高表达者13例确诊部分缓解，28例病情稳定（客观缓解率20.3%，95%可信区间[CI]: 12.3% ~ 31.7%, p < 0.0001）；中位缓解持续时间为6.7个月，中位进展时间为3.7个月（95% CI: 2.7-5.1个月）。中度表达者有2例确诊部分缓解（客观缓解率为7.1%;95% CI: 2.0% ~ 22.7%, p = 0.4117）， 15例病情稳定。78.3%的患者（72/92）发生了治疗后出现的不良事件（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。最常见的治疗突发事件包括虚弱（37.0%）、角膜炎（29.3%）和呼吸困难（23.9%）。角膜不良事件发生率为38.0%(35/92)，通常为1/2级，可逆，通过剂量调整可控制。结论usamitamab ravtansine在ceacam5高表达NSq NSCLC患者中具有良好的安全性、客观疗效和抗肿瘤活性。

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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

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.

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