Siu Lillian L, Hong David S, Döcke Wolf-Dietrich, Tetzner Reimo, Trautwein Mark, Phelps Charles, Willuda Joerg, Yu Xiang Qing, Nogai Hendrik, Johnson Melissa, Goh Boon Cher
Princess Margaret Cancer Centre, University Health Network, University of Toronto, 700 University Avenue, Suite 7-624, Toronto, M5G 1Z5, Canada.
The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Target Oncol. 2025 Jun 4. doi: 10.1007/s11523-025-01154-4.
Tinurilimab is a humanized immunoglobulin G subclass 2 antibody that blocks carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), an immune checkpoint regulator that is overexpressed in several tumor types.
This phase I study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and tumor response profile of tinurilimab in patients with advanced solid tumors with a described expression of CEACAM6.
In this first-in-human, dose-escalation and dose-expansion study, tinurilimab was administered as a 1-h intravenous infusion in 21-day cycles at a starting dose of 2.5 mg, with a planned escalation up to 1800 mg. Following observation of treatment toxicity (cytokine release syndrome in one patient and neutropenia in all patients treated at 30 mg), a premedication regimen was initiated that included dexamethasone 8 mg before and after dosing. Thirty patients received treatment across six dosing cohorts (2.5-100 mg with or without dexamethasone).
The maximum tolerated dose was not determined, as the study was terminated due to an unfavorable benefit/risk assessment. All 30 patients (100%) treated with tinurilimab experienced at least one treatment-emergent adverse event of any grade, most commonly fatigue (36.7%), infusion-related reaction (30.0%), and neutropenia (26.7%). The most common grade ≥ 3 treatment-related adverse events were neutropenia (23.3%), followed by febrile neutropenia, cytokine release syndrome, increased hepatic enzymes, decreased lymphocyte count, hypophosphatemia, lactic acidosis, and acute kidney injury (3.3% each). No patients reported an objective response.
Following study termination, the clinical development program for tinurilimab was discontinued permanently.
www.
gov , NCT03596372.
替雷利珠单抗是一种人源化免疫球蛋白G2亚类抗体，可阻断癌胚抗原相关细胞黏附分子6（CEACAM6），这是一种在多种肿瘤类型中过表达的免疫检查点调节因子。
本I期研究评估了替雷利珠单抗在具有所述CEACAM6表达的晚期实体瘤患者中的安全性、耐受性、药代动力学、药效学和肿瘤反应情况。
在这项首次人体剂量递增和剂量扩展研究中，替雷利珠单抗以2.5mg的起始剂量在21天周期内进行1小时静脉输注给药，计划剂量递增至1800mg。在观察到治疗毒性（1例患者出现细胞因子释放综合征，所有接受30mg治疗的患者均出现中性粒细胞减少）后，启动了预处理方案，包括给药前和给药后使用8mg地塞米松。30名患者在六个给药队列（2.5 - 100mg，有或无地塞米松）中接受治疗。
由于获益/风险评估不利，该研究提前终止，未确定最大耐受剂量。所有30名接受替雷利珠单抗治疗的患者（100%）均经历了至少1次任何级别的治疗期间出现的不良事件，最常见的是疲劳（36.7%）、输液相关反应（30.0%）和中性粒细胞减少（26.7%）。最常见的≥3级治疗相关不良事件是中性粒细胞减少（23.3%），其次是发热性中性粒细胞减少、细胞因子释放综合征、肝酶升高、淋巴细胞计数减少、低磷血症、乳酸酸中毒和急性肾损伤（各3.3%）。没有患者报告客观缓解。
研究终止后，替雷利珠单抗的临床开发项目永久停止。
