Biopharmaceutical company Endocyte, Inc.has dosed its first patient in phase I clinical trial in advanced solid tumours for its SMDC EC1456, a folate receptor (FR)-targeting folate-tubulysin conjugate.
The open-label, multi-centre, non-randomized, dose-escalation study is divided into two parts. The first part of the phase I study will evaluate the maximum tolerated dose (MTD) and recommended phase II dose of EC1456 in patients with metastatic or locally advanced solid tumours, the primary endpoint of the study.
The second part of the study will determine the efficacy of EC1456 in patients with select cancers known to express the folate receptor with all target lesions positive for FR [FR(100%)] and treated with MTD. The FRstatus will be determined using the investigational companion imaging agent, etarfolatide (EC20).
“We continue to expand our SMDC portfolio and companion imaging agents as we move our second drug candidate, EC1456, into the clinic,” said Ron Ellis, president and CEO of Endocyte. “Our companion imaging agent, etarfolatide, is being investigated to identify cancer patients who express the folate receptor and are likely to respond to this targeted and highly potent drug conjugate. The possibility to utilize molecular analysis to manage an individual patient’s disease is the hallmark of precision medicine and having the possibility to evaluate a disease status or all of a patient’s cancer lesions in real time will help to achieve optimal medical outcomes for patients and physicians.”
Christopher Leamon, Ph.D., vice president of research of Endocyte, added, “EC1456 combines the FR precision targeting component of vintafolide with the extremely potent cytotoxic molecule, tubulysin. As demonstrated with strong preclinical data, EC1456 holds promise for treating FR-positive patients who have become resistant to other drugs, such as paclitaxel and vintafolide as well as cancers that express lower levels of the folate receptor.”
The first part of the study will enroll an estimate of 30 patients with metastatic or locally advanced solid tumours who have failed to respond to standard therapy if available. The second part of the study will enroll 10 patients each with the advanced solid cancer indication, such as triple-negative breast cancer (TNBC), advanced non-small cell lung cancer (NSCLC), ovarian cancer and hepatocellular carcinoma (HCC), who have received no more than two prior chemotherapies. Secondary endpoints include safety profile of EC1456, efficacy and pharmacokinetic analysis as well as the correlation between baseline folate expression measured by etarfolatide scans and antitumor activity of EC1456.
EC1456 is an investigational proprietary, injectable, SMDC consisting of folate (vitamin B9) linked to a potent cytotoxic agent, tubulysin B hydrazide (TubBH). EC1456 is wholly owned by Endocyte. TubBH is a member of the tubulysin class of anti-neoplastic agents that inhibit the polymerization of tubulin into microtubules, a critical component during cell division. The targeting ligand folate, essential for cell division, has been investigated with vintafolide. EC1456 is currently being evaluated in a phase I study in patients with advanced solid tumours (Clinicaltrials.gov NCT01999738).
Etarfolatide is an investigational FR-targeted companion imaging agent that is being developed as a noninvasive method to identify tumours that express the FR. These tumours are the molecular target of Endocyte's FR-targeted therapeutic compounds such as vintafolide and EC1456. Folic acid is used with etarfolatide for the enhancement of image quality. Etarfolatide is under review with the EMA and has been granted orphan drug status by the European Commission.