US-based biopharmaceutical firm Endocyte has dosed its first patient in its open-label, multicentre, non-randomised, dose-escalation Phase I clinical trial, designed to evaluate SMDC EC1456, a folate receptor (FR)-targeting folate-tubulysin conjugate in advanced solid tumours.
The Phase I trial is divided into two parts under which the first part will assess 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 trial.
The second part of the trial will evaluate 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 FR-status will be assessed using the investigational companion imaging agent, etarfolatide (EC20).
Endocyte president and CEO Ron Ellis said the company's 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 utilise 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," Ellis said.
Endocyte vice-president of research Christopher Leamon said 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," Leamon said.
Some 30 patients will be enrolled in the first part of the trial, having metastatic or locally advanced solid tumours and who have failed to respond to standard therapy if available.
The second part of the trial will enrol ten 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 of the trial include safety profile of EC1456, efficacy and pharmacokinetic analysis as well as the correlation between baseline folate expression measured by etarfolatide scans and antitumour activity of EC1456.