Targeted failure of the week. Post No 57. Cerulean's CRLX101

From here:

Cerulean Pharma Inc. (Cambridge, Mass.) said CRLX101 given every other week plus best supportive care missed the primary endpoint of improving median overall survival (OS) vs. best supportive care alone in a Phase IIb trial to treat advanced non-small cell lung cancer (NSCLC). The open-label, Russian and Ukrainian trial enrolled 157 patients who progressed after one to two regimens of chemotherapy. Cerulean declined to disclose details. The company said it will focus on its other cancer programs for CRLX101 instead of continuing research in NSCLC.

And what is CLRX101? According to wikipedia (from 20130323):

CRLX101 is a novel approach to cancer chemotherapy that is currently under investigation in human trials, and is an example of a nanomedicine.

The agent represents a nanoparticle conjugate that consists of a drug delivery molecule, namely a cyclodextrin-based polymer (CDP) and an anti-cancer compound (camptothecin). It was developed by Dr. Mark E. Davis, professor of Chemical Engineering at the California Institute of Technology, and associates at Insert Therapeutics, Inc., now Calando Pharmaceuticals, Inc., hence the original name "IT-101". Its novel delivery mode allows the agent, and thus the toxic anti-cancer component, to be preferentially accumulated in cancer tissue. In turn, toxic side effect are expected to be reduced. The technology was licensed by Calando and Caltech to Cerulean Pharma Inc., in June, 2009.

Ok, nanomedicine fails as it was expected (I have written that nanomedicine sucks here) but it is interesting what was the rationale to use it - let's read t in wiki:

Rationale

Camptothecin (CPT), an alkaloid extract with poor water solubility from plants such as camptotheca acuminata, exhibits anti-cancer activity possibly due, at least in part, by the inhibition of DNA topoisomerase I resulting in cell death. In CRLX101, CPT is linked covalently through a glycine link to the linear copolymer CDP, which in turn consists of alternating subunits of beta-cyclodextrin and polyethylene glycol (PEG). The CRLX101 nanoparticle is water soluble. After intravenous injection, active CPT is slowly released as the linkage is hydrolysed. The size of the nanoparticle (20-50 nm in diameter) facilitates its extravasation in the more leaky vessels of tumors via the enhanced permeability and retention effect and as a result, the anticancer drug is enhanced and retained in the tumor tissue.

 

The rational - is a very old mantra which seems to e not rational anymore...