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New Cancer Drug ETC-159 Enters Phase 1B of Clinical Trials

Cancer drug developed in Singapore by Duke-NUS Medical School and the Agency for Science, Technology and Research (A*STAR) with applications in cancer immunotherapy takes its first steps into the next phase of clinical trials.

The journey of a newly developed drug from the lab bench to the pharmacy is a long and difficult one. Several rounds of research are required before a new drug is created before pre-clinical testing is carried out. Only when in vitro and in vivo testing both show promising results will the drug be considered for clinical trials in humans. It gets more challenging from here, but even getting to this point is no small feat.

Clinical trials consist primarily of three phases. In Phase 1, it is tested on a small number of healthy volunteers and patients in order to evaluate its safety, and to learn about its potential side effects. If everything goes well, the drug moves on to Phase 2, where it is tested on a few dozen to hundreds of patients. The drug’s efficacy, safety, and appropriate dosage is evaluated at this stage, and only a few drug candidates move on to the third phase of clinical trials. Phase 3 includes testing on hundreds to thousands of patients and explores the safety and efficacy of the new drug, this time in comparison with other currently available treatments.

Even after passing through clinical trials, the new drug has to undergo review by authorities to confirm that it is a safe and effective treatment. In the case that it is approved, it still has to undergo long-term evaluation in a large number of patients, since some adverse effects can take a long time to surface.

This whole process is highly rigorous and can take anywhere between five to 15 years, making any progress along this pathway a cause for celebration for its developers.

A new cancer drug developed in Singapore, known as ETC-159, has reached the next phase of testing in clinical trials. ETC-159 was developed in a partnership between Duke-NUS Medical School (Duke-NUS) and the Agency for Science, Technology and Research (A*STAR). It has come a long way since it was first entered into clinical trials in June 2015.

Phase 1A of clinical trials for ETC-159 was completed in July 2018, thanks to the efforts of A*STAR’s Experimental Drug Development Centre (EDDC). During the trial, the mechanism of action of ETC-159 was validated, and a safe dosage level established in patients with advanced solid tumours.

ETC-159 has reached “First Patient First Visit” in Phase 1B. This means the first completed administration of the first dose of the drug to the first patient at the patient’s first visit in a Phase 1 clinical trial. The clinical trials will include a range of cancer patients from Singapore and the United States. This phase of the clinical trial is expected to reach completion before the end of 2023.

Tests in Phase 1B will involve a specific subgroup of colorectal cancer patients with R-spondin gene fusions in their tumours. Patients with such gene fusions are believed to respond well to ETC-159 treatment and will be specially selected for the purposes of this trial. The EDDC has collaborated other A*STAR institutions, including POLARIS3 at the Genome Institute of Singapore (GIS) and the Diagnostics Development (DxD) Hub, to establish a novel diagnostic test approved by the United States Food and Drug Administration, in order to identify patients with R-spondin gene fusions.

ETC-159 is a promising treatment for several forms of cancer, including colorectal, endometrial, ovarian, and pancreatic cancers. Its primary mechanism is by acting on the Wnt pathway, a signal transduction pathway that is well-known for its role in embryonic development, as well as in carcinogenesis.

Dysregulation or upregulation of the Wnt pathway has been implicated in several cancers and has been associated with poorer treatment outcomes. This is resulted from the upregulation of the Wnt pathway which prevents immune cells from accessing cancer cells in tumours.

ETC-159 blocks the Wnt pathway by acting as an upstream inhibitor, thereby allowing immune cells to access and enter the tumour. Trials will also administer ETC-159 together with pembrolizumab, a therapeutic antibody that binds to receptors on immune cells in order to stimulate them to kill cancer cells. Should this trial be successful, ETC-159 could be used to boost the effects of immunotherapy.

The success of ETC-159 thus far has been described by Professor Damian O’Connell, Chief Executive Officer of EDDC, as “a significant milestone for EDDC and Singapore” – a sentiment shared by Professor David Virshup from Duke-NUS, who describes the progress of ETC-159 as “the result of a tremendous Singapore team effort, spanning from basic bench science to international clinical trials.” [APBN]