Park David J, Thura Min, Chiu Vi K, Vicuna Brian, Ang Koon Hwee, Sanchez Blanca, Chia Pei Ling, Kuan Kam Yew, Li Jie, Zhang Ke, Zheng Wei Hui, Hsien Ng Matthew Chau, Zeng Qi
St Jude Crosson Cancer Institute/ Providence Medical Foundation, St. Jude Heritage Medical Group, Fullerton, CA, USA.
Institute of Molecular and Cell Biology (IMCB), Agency for Science Technology and Research (A∗STAR), 61 boipolis drive, Singapore 138673, Singapore.
Cell Rep Med. 2025 May 20;6(5):102120. doi: 10.1016/j.xcrm.2025.102120. Epub 2025 May 8.
This Food and Drug Administration (FDA)-approved phase 2 basket trial has three highlights: (1) PRL3, an intracellular oncotarget that is highly (∼80.6%) expressed in multiple cancers; (2) PRL3-zumab, the first-in-class humanized antibody (immunoglobulin G1 [IgG1]) with high affinity to PRL3 (K = 7.57 pM); and (3) proof of concept: targeting intracellular oncoprotein with antibody-based therapy. A full analysis set (FAS, 51 patients received ≥1 dose) is used for pharmacokinetic and safety studies. Out of FAS, 20 patients are eligible to constitute the efficacy evaluable set (EES). To circumvent the heterogeneities from different individuals/cancers, we propose single evaluable patient single cohort (SEPSC) and apply comparison using double stringent/rigorous controls with (1) historical progression-free survival (PFS) and (2) prior lines' PFS within the same patients. PRL3-zumab shows longer PFS than prior line(s) of anti-PD-(L)1 therapies. PRL3-zumab demonstrates excellent safety and clear clinical benefits in late-stage IV solid cancer patients. This trial is registered at ClinicalTrials.gov as NCT04452955.
这项获得美国食品药品监督管理局（FDA）批准的2期篮子试验有三个亮点：（1）PRL3，一种在多种癌症中高表达（约80.6%）的细胞内致癌靶点；（2）PRL3-zumab，首个对PRL3具有高亲和力（K = 7.57 pM）的人源化抗体（免疫球蛋白G1 [IgG1]）；（3）概念验证：用基于抗体的疗法靶向细胞内癌蛋白。完整分析集（FAS，51例患者接受了≥1剂治疗）用于药代动力学和安全性研究。在FAS中，20例患者符合构成疗效可评估集（EES）的条件。为了规避不同个体/癌症的异质性，我们提出单可评估患者单队列（SEPSC），并采用双重严格对照进行比较，即（1）历史无进展生存期（PFS）和（2）同一患者先前治疗线的PFS。PRL3-zumab显示出比先前抗PD-（L）1治疗线更长的PFS。PRL3-zumab在晚期IV期实体癌患者中显示出优异的安全性和明确的临床益处。该试验已在ClinicalTrials.gov上注册，注册号为NCT04452955。
