Cyclodextrin-containing polymer (CDP) (represented by blue in the scheme) conjugated to camptothecin (CPT) (represented by red) forms 30-40-nm diameter nanoparticles (NPs). These NPs show enhanced tumor permeation and retention via fenestrations in neo-vasculature. They can enter the tumor cells and are not effluxed by multidrug resistance pumps. Camptotecin, a potent inhibitor of both topoisomerase 1 and HIF-1a, is gradually released from NPs within the tumor cells.
The phase 1/2a clinical trial for treatment of advanced solid tumor malignancies was concluded in 2013. Both safety and efficacy of NPs were established paving the way for further trials. Some of them are still going on, others to be started soon.
Cyclodextrin-based polymer-camptothecin CRLX101 and Olaparib in Treating Patients with Refractory Advanced Solid Tumors, Relapsed or Refractory Small Cell Lung Cancer, or Metastatic Urothelial or Castration-Resistant Prostate Cancer
started in 2016 to be finished in 2022
CRLX101 and Enzalutamide in Treating Participants with Progressive Metastatic Castration Resistant Prostate Cancer
to be started in 2018