Issues

Tabernero and colleagues report the results of a phase I dose-escalation and expansion study assessing the safety, activity, and pharmacodynamics of ALN-VSP, a lipid nanoparticle containing siRNAs against vascular endothelial growth factor A (VEGFA) and kinesin spindle protein (KSP), in patients with advanced solid tumors with liver involvement. One patient with metastatic endometrial cancer had a complete response and 3 patients (2 with metastatic renal cell carcinoma and 1 with metastatic pancreatic neuroendocrine tumor) experienced disease stabilization. Post-treatment tumor biopsies showed evidence of intratumoral delivery, increased VEGFA mRNA cleavage, and decreased VEGFA and KSP mRNA levels compared with pre-treatment biopsy samples, consistent with an on-target response and an RNAi mechanism of action. For details, please see the article by Tabernero and colleagues on page 406.