The final overall survival (OS) analysis from the Phase IIb TARGET trial evaluating Endocyte’s small molecule drug conjugate (SMDC) vintafolide in combination with docetaxel in patients with Folate Receptor (FR) positive recurrent Non-Small Cell Lung Cancer (NSCLC) presented at the World Conference on Lung Cancer (WCLC) in Denver, Colorado, being held September 6 – 9, 2015, show positive results. The results supports the idea that FR is a valid target in NSCLC. [1]

Vintafolide, a folic acid-vinca alkaloid conjugate,  is an investigational, proprietary, injectable SMDC consisting of folate (vitamin B9) linked to a potent vinca alkaloid cytotoxic agent, desacetylvinblastine hydrazide or DAVLBH. The drug is designed to selectively target the folate receptor to deliver the anti-cancer agent to the cancerous tissue. The drug binds to the folate receptor, which is overexpressed in approximately 80% of patients with NSCLC, including patients with squamous cell and adenocarcinoma.

Tumors that have high concentrations of the folate receptor are identified by etarfolatide (99mTc-etarfolatide), a non-invasive molecular imaging diagnostic agent used f0r SPECT imaging.


Vintafolide has demonstrated single agent activity in patients with advanced NSCLC whose tumors all expressed FR [FR(100%)] vs.patients not FR(100%)

Improved overal survival
Vintafolide plus docetaxel improved overall survival by 2.7 months in NSCLC regardless of histology (Median OS 11.5 vs. 8.8 months, OS HR=0.86, 95% CI [0.58, 1.26]). In the predefined subset analysis of patients with adenocarcinoma, which expresses higher levels of folate receptor, vintafolide plus docetaxel improved OS by 5.9 months (12.5 vs. 6.6 months, HR=0.72, 95% CI [0.44, 1.16]). OS for vintafolide as single agent was similar to docetaxel (OS 8.4 vs. 8.8 months, HR=1.02, 95% CI [0.70, 1.50]).[1]

The study previously reported that the PFS primary endpoint was met, (HR=0.75, 95% CI [0.52, 1.09]) regardless of histology and in the adenocarcinoma subgroup (HR=0.73, 95% CI [0.46, 1.16]). The safety profile of the combination arm was consistent with those observed with docetaxel alone and vintafolide alone, though a higher rate of hematologic and peripheral neuropathy adverse events were observed in the combination arm.

“The final OS results are consistent with the biology of the folate receptor target, with higher expression levels in the adenocarcinoma subgroup. These data are important in guiding our future studies in NSCLC,” noted Ron Ellis, president and CEO at Endocyte.

A more potent drug
“Based on the results to date from the ongoing Phase I dose escalation trial of EC1456, we are optimistic that this agent will represent an important improvement in the treatment landscape for NSCLC,” added Alison Armour, Endocyte’s Chief Medical Officer.

EC1456 is a second generation folate-targeted SMDC consisting of folate linked to a potent cytotoxic agent, tubulysin B hydrazide (TubBH), which delivers a more potent drug payload at higher doses than vintafolide. The trial drug includes an advanced spacer/linker to allow for potentially higher dosing in spite of a more potent payload than vintafolide

EC1456 is currently being evaluated in a Phase I study ( Identifier: NCT01999738)  in patients with advanced solid tumors.