AMG 119,首个针对 Delta 样配体 3(DLL3)的嵌合抗原受体 T(CAR-T)细胞疗法,用于治疗复发/难治性小细胞肺癌(SCLC)患者的临床药理学特征。
Clinical Pharmacology Profile of AMG 119, the First Chimeric Antigen Receptor T (CAR-T) Cell Therapy Targeting Delta-Like Ligand 3 (DLL3), in Patients with Relapsed/Refractory Small Cell Lung Cancer (SCLC).
机构信息
Clinical Pharmacology, Modeling & Simulation, Amgen Inc, South San Francisco, CA, USA.
Thoracic Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA.
出版信息
J Clin Pharmacol. 2024 Mar;64(3):362-370. doi: 10.1002/jcph.2346. Epub 2023 Oct 2.
With the promise of a potentially single-dose curative regimen, CAR-T cell therapies have brought a paradigm shift in the treatment and management of hematological malignancies with 6 approved products in the USA. However, there are no approved CAR-T cell therapies for solid tumors. Herein, we report the clinical pharmacology profile of AMG 119, the first CAR-T cell therapy targeting delta-like ligand 3 (DLL3), in patients with relapsed/refractory (R/R) small cell lung cancer (SCLC). AMG 119 demonstrated robust cellular expansion with long-lasting cell persistence and a favorable exposure-response relationship. AMG 119 has been demonstrated to be clinically safe and well tolerated at the doses tested, with no dose-limiting toxicities (DLTs) reported. This is the first publication of the clinical pharmacology profile of a CAR-T cell therapy in SCLC, with encouraging cellular kinetics data supporting the potential for CAR-T cell therapy in solid tumor space.
凭借潜在的单剂量治愈方案的承诺,嵌合抗原受体 T 细胞疗法(CAR-T 细胞疗法)在治疗和管理血液系统恶性肿瘤方面带来了范式转变,美国已有 6 种获批产品。然而,目前尚无针对实体瘤的获批 CAR-T 细胞疗法。在此,我们报告了靶向 delta 样配体 3(DLL3)的首个 CAR-T 细胞疗法 AMG 119 在复发/难治性(R/R)小细胞肺癌(SCLC)患者中的临床药理学特征。AMG 119 表现出强大的细胞扩增,具有持久的细胞持久性和有利的暴露-反应关系。在测试的剂量下,AMG 119 已被证明是临床安全且耐受良好的,没有报告剂量限制性毒性(DLTs)。这是 CAR-T 细胞疗法在 SCLC 中的临床药理学特征的首次出版物,令人鼓舞的细胞动力学数据支持 CAR-T 细胞疗法在实体瘤领域的潜力。