SAN FRANCISCO, Feb. 05, 2024 (GLOBE NEWSWIRE) -- ProLynx Inc. announced today that the first patient was treated with PLX038 (PEGylated SN-38) in a Phase I/II clinical trial for primary CNS tumors driven by MYC or MYCN amplifications. National Institutes of Health’s NCI investigators Dr. Marta Penas-Prado and Dr.

旧金山，2024年2月5日（环球通讯社）--ProLynx Inc.今天宣布，在由MYC或MYCN扩增驱动的原发性中枢神经系统肿瘤的I/II期临床试验中，第一名患者接受了PLX038（聚乙二醇化SN-38）治疗。美国国立卫生研究院NCI研究员MartaPenasPrado博士和。

Mark Gilbert are conducting the trial. MYC genes regulate expression of genes involved in cell division. High levels of MYC drive oncogenesis in many cancers and induce DNA changes leading to the formation of “topoisome complexes”. MYC and MYCN amplifications are seen in multiple primary tumors of the central nervous system (CNS).

马克·吉尔伯特正在主持审判。MYC基因调节参与细胞分裂的基因的表达。高水平的MYC驱动许多癌症的肿瘤发生，并诱导DNA变化，导致“拓扑体复合物”的形成。在中枢神经系统（CNS）的多个原发性肿瘤中可见MYC和MYCN扩增。

This includes 30% of relapsed medulloblastomas, and MYCN-amplified ependymoma, characterized by aggressive clinical behavior and treatment resistance. The MYC or MYCN-induced topoisome contains high levels of topoisomerases that should be susceptible to topoisomerase inhibitors. PLX038 is a long-acting prodrug of the topoisomerase 1 inhibitor, SN-38 – the active metabolite of irinotecan and sacituzumab govitecan.

这包括30%的复发性髓母细胞瘤和MYCN扩增的室管膜瘤，其特征是具有侵略性的临床行为和治疗抵抗力。MYC或MYCN诱导的拓扑异构酶含有高水平的拓扑异构酶，应该对拓扑异构酶抑制剂敏感。PLX038是拓扑异构酶1抑制剂SN-38的长效前药，SN-38是伊立替康和sacituzumab-govitecan的活性代谢产物。

PLX038 is unique as the SN-38 is covalently bound to a circulating nanomolecule and is slowly released to provide free SN-38 with a long half-life, low Cmax and very high exposure – important for optimal safety and efficacy. Importantly, in preclinical studies, PLX038 was shown to accumulate in CNS tumors, where it slowly releases SN-38.

PLX038是独特的，因为SN-38与循环纳米分子共价结合，并缓慢释放，以提供具有长半衰期，低Cmax和非常高暴露的游离SN-38，这对于最佳安全性和有效性很重要。重要的是，在临床前研究中，PLX038被证明在中枢神经系统肿瘤中积累，并缓慢释放SN-38。

The NCI trial will assess whether PLX038 is safe and efficacious in primary CNS tumors driven by MYC or MYCN amplifications. The Phase I trial will confirm the recommended Phase II dose. The Phase II trial will test PLX038 in 3 independent cohorts: 1) newly diagnosed MYCN-amplified ependymoma, 2) recurrent ependymoma or medulloblastoma with MYCN or MYC amplification, and 3) other recurrent .

NCI试验将评估PLX038在由MYC或MYCN扩增驱动的原发性中枢神经系统肿瘤中是否安全有效。I期试验将确认推荐的II期剂量。II期试验将在3个独立队列中测试PLX038：1）新诊断的MYCN扩增的室管膜瘤，2）MYCN或MYC扩增的复发性室管膜瘤或髓母细胞瘤，以及3）其他复发性。