First-In-Human Trial Of Microrna Cancer Therapy With Mrx34, A Liposomal Mir-34 Mimic: Phase Ia Expansion In Patients With Advanced Solid Tumors.

TPS2597Background: MicroRNAs (miRNAs) are naturally occurring, short (~22 nucleotides), non-coding single-stranded RNAs that comprise a new class of post-transcriptional regulators of gene expression. Each miRNA modulates the expression of hundreds of genes across distinct cellular pathways. This broad activity gives miRNA-based therapy the potential to simultaneously repress multiple oncogenic processes in the tumor microenvironment, including growth and proliferation, resistance, cancer stem cells, metastasis, and immune evasion. The tumor suppressor miRNA miR-34a has been shown to down-regulate expression of u003e 30 oncogenes (eg, MET, MEK1, PDGFR-α, CDK4/6, BCL2, WNT 1/3, NOTCH1, CD44), as well as genes involved in tumor immune evasion (eg, PD-L1, DGKζ). MRX34, a liposome-encapsulated miR-34a mimic, is a potential first-in-class miRNA therapy for cancer. Methods: The initial standard 3x3 dose-escalation portion of this trial (NCT01829971) is complete; here we describe the on-going phase Ia expansion in w...