Made-In-Singapore Cancer Drug ETC-159 Advances In Clinical Trials

06 June 2022 | Monday | News

The Phase 1B dose expansion study will have two groups.
Image Source : Public Domain

Image Source : Public Domain

A made-in-Singapore cancer drug, ETC-159, has advanced into the dose expansion  portion of its Phase 1B clinical trial. The Phase 1B dose expansion study tests the  preliminary efficacy and safety of ETC-159 in a subset of genetically defined patients  with microsatellite stable (MSS)1 cancers. MSS tumours have few genetic  aberrations and patients are usually unresponsive to immunotherapy like  pembrolizumab, a checkpoint inhibitor used in the treatment of many cancers. To  date, the first portion of the Phase 1B trial, the dose escalation study, has been  completed and a safe dose of ETC-159 in combination with pembrolizumab has  been defined. ETC-159 was previously shown to be safe as a monotherapy in its  Phase 1A trial. 


ETC-159 was jointly developed by Duke-NUS Medical School (Duke-NUS) and the  Experimental Drug Development Centre (EDDC), a national platform for drug  discovery and development hosted by the Agency for Science, Technology and  Research (A*STAR). This small molecule drug targets a range of solid tumours  including colorectal, endometrial, ovarian and pancreatic cancers, which contribute  to a significant fraction of Singapore’s cancer burden. A subset of these cancers are  caused by hyperactivity in a cell signalling pathway known as the Wnt pathway. 

The Phase 1B dose expansion study will have two groups.  

  • In one group, ETC-159 will be tested as a monotherapy in MSS colorectal cancer (CRC) patients who have a specific genetic mutation, called “RSPO Fusion”. This mutation is present in about 8% of CRC patients and it activates the Wnt pathway, making these patients sensitive to Wnt inhibitors like ETC 159. A diagnostic test designed by EDDC was manufactured and clinically  validated at POLARIS @ A*STAR’s Genome Institute of Singapore  (GIS). Supported by the Diagnostics Development (DxD) Hub, this test will be  used to select colorectal cancer patients with RSPO Fusion to participate in  the trial. RNA Extraction from Formalin-Fixed Paraffin-Embedded (FFPE)2 tissue samples followed by testing of Fusion genes will be done at POLARIS  @ GIS. 

2 A technique used to preserve and prepare tissue specimens (e.g.: samples from cancer biopsies) for  examination, research or drug/diagnostic development. 

ETC-159 Dose Expansion – News Update 

  • In the second dose expansion patient group, ETC-159 will be tested in  combination with the immune checkpoint inhibitor pembrolizumab in MSS  colorectal cancer patients who do not have RSPO fusions, as well as in  patients with MSS endometrial and MSS ovarian cancers. The ability of ETC 159 to sensitise MSS cancers to pembrolizumab will be investigated. The combination of ETC-159 and pembrolizumab has been demonstrated to be  synergistic in preclinical studies. 

EDDC Development team discussing the ETC-159 dose expansion study 

As in earlier trials, investigators will track the biological effect of ETC-159, also  known as its pharmacodynamics, in patients participating in the dose expansion  study. The pharmacodynamics of a drug can be measured from tumour samples  taken through biopsies, such as during surgery or an invasive procedure. EDDC  established that it will also be possible to measure the pharmacodynamics of the  drug through monitoring the levels of Axin2 mRNA in hair follicles. Axin2 is a  downstream protein in the Wnt pathway, and its levels are reduced when ETC-159  effectively acts on the pathway. This minimally invasive measurement of ETC-159’s  biological effect will allow investigators to understand how well the drug is working in  patients over the course of study.  

Patients for the dose expansion study will come from two sites in Singapore as well  as seven sites in the United States. The trial is expected to be completed by 2024. 


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