Muro Kei, Yamazaki Kentaro, Kadowaki Shigenori, Mishima Saori, Kawakami Takeshi, Tanaka Tomoyuki, Tada Keisuke, Fagniez Nathalie, Ohshima Shinobu, Yoshino Takayuki
Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
Int J Clin Oncol. 2025 May 25. doi: 10.1007/s10147-025-02784-4.
Tusamitamab ravtansine (SAR408701) is an immunoconjugate that binds carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and delivers its cytotoxic payload to target cells. Here, we report findings from three dosing regimens of tusamitamab ravtansine administration in Japanese adults with advanced malignant solid tumors.
Japanese adults (aged ≥ 20 years) with CEACAM5-expressing malignant solid tumors were enrolled in this Phase 1, open-label, non-randomized, dose-escalation evaluation of tusamitamab ravtansine in three parts: (i) main dose-escalation part with every two weeks (Q2W) administration, (ii) loading dose (LD) part with Q2W administration with a LD at Cycle 1 (C1) only, and (iii) dose-escalation every three weeks (Q3W) part. Primary objectives were to evaluate the tolerability and safety of tusamitamab ravtansine.
Nine patients were enrolled in the main dose-escalation part, 16 patients in the dose-escalation bis part with LD, and nine patients in the dose-escalation Q3W part. Administration of tusamitamab ravtansine resulted in a manageable safety profile with no dose-limiting toxicities reported during the observation period except for two events during dose-escalation bis Q2W part. Most common adverse events (AEs) were corneal events, gastrointestinal disorders, and metabolic events. After first administration, tusamitamab ravtansine exposure was dose proportional over the dose range 80-170 mg/m. Best overall response (BOR) was stable disease, observed in all three parts; confirmed response was not observed at any dose level.
Tusamitamab ravtansine demonstrated a tolerable safety profile at a dose of 80-170 mg/m in three different administration schedules in Japanese adults with metastatic solid tumors.
图萨米他单抗拉凡他辛（SAR408701）是一种免疫缀合物，可结合癌胚抗原相关细胞粘附分子5（CEACAM5），并将其细胞毒性载荷传递至靶细胞。在此，我们报告图萨米他单抗拉凡他辛在日本晚期恶性实体瘤成人患者中的三种给药方案的研究结果。
将表达CEACAM5的恶性实体瘤日本成人患者（年龄≥20岁）纳入这项1期开放标签、非随机、剂量递增评估，图萨米他单抗拉凡他辛的评估分为三个部分：（i）每两周（Q2W）给药的主要剂量递增部分，（ii）仅在第1周期（C1）给予Q2W给药并带有负荷剂量（LD）的负荷剂量（LD）部分，以及（iii）每三周（Q3W）给药的剂量递增部分。主要目标是评估图萨米他单抗拉凡他辛的耐受性和安全性。
主要剂量递增部分纳入9例患者，负荷剂量部分纳入16例采用Q2W给药且仅在C1给予LD的患者，剂量递增Q3W部分纳入9例患者。图萨米他单抗拉凡他辛的给药导致安全性可控，观察期内除了在剂量递增Q2W部分出现的两起事件外，未报告剂量限制性毒性。最常见的不良事件（AE）为角膜事件、胃肠道疾病和代谢事件。首次给药后，在80 - 170mg/m的剂量范围内，图萨米他单抗拉凡他辛的暴露量与剂量成比例。最佳总体缓解（BOR）为病情稳定，在所有三个部分均观察到；在任何剂量水平均未观察到确认的缓解。
在日本转移性实体瘤成人患者中，图萨米他单抗拉凡他辛在三种不同给药方案下，剂量为80 - 170mg/m时显示出可耐受的安全性。
