- |||||||||| ETC-159 / Experimental Therapeutics Centre, A*Star, National University of Singapore
Journal: Examination of Wnt signaling as a therapeutic target for pancreatic ductal adenocarcinoma (PDAC) using a pancreatic tumor organoid library (PTOL). (Pubmed Central) - Apr 14, 2024
The clinical utilization of this combinatory treatment modality in pancreatic cancer PDOs has thus far been supported in our patient-derived xenograft models treated with Wnt inhibitor plus paclitaxel or gemcitabine. Gene expression analysis suggests there are key Wnt genes that contribute to the Wnt (in)dependent phenotypes of pancreatic tumors, providing plausible mechanistic explanation for Wnt (in)dependency and susceptibility or resistance to treatment on the genotypic level.
- |||||||||| COVID-19 antibody / Roche, A*Star
Trial completion, Enrollment change, Trial completion date: SCAPE-HIV: SARS-CoV-2 (COVID-19) Antibody PrevalencE in an Adult London HIV Cohort (clinicaltrials.gov) - Nov 27, 2023
P=N/A, N=615, Completed,
These results confirmed new evidence for therapeutic perspective of TC-derived Exo in IUAs. Recruiting --> Completed | N=1500 --> 615 | Trial completion date: Apr 2022 --> Jun 2023
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), ETC-159 / Experimental Therapeutics Centre, A*Star, National University of Singapore
Enrollment closed, Trial completion date, Trial primary completion date, Combination therapy, Metastases: A Study to Evaluate the Safety and Tolerability of ETC-1922159 as a Single Agent and in Combination With Pembrolizumab in Advanced Solid Tumours (clinicaltrials.gov) - Nov 8, 2023
P1, N=89, Active, not recruiting,
Recruiting --> Completed | N=1500 --> 615 | Trial completion date: Apr 2022 --> Jun 2023 Recruiting --> Active, not recruiting | Trial completion date: Aug 2024 --> May 2024 | Trial primary completion date: Dec 2022 --> Feb 2024
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), EBC-129 / A*Star, National Cancer Centre Singapore
Trial completion date, Trial primary completion date, Combination therapy, Metastases: A Study of EBC-129 in Advanced Solid Tumours (clinicaltrials.gov) - Oct 13, 2023
P1, N=84, Recruiting,
SAEs were pneumonitis and erythema with fever (8 mg, 1 patient). Trial completion date: May 2025 --> Jun 2026 | Trial primary completion date: Apr 2025 --> Jun 2026
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), EBC-129 / A*Star, National Cancer Centre Singapore
Enrollment open, Combination therapy, Metastases: A Study of EBC-129 in Advanced Solid Tumours (clinicaltrials.gov) - May 25, 2023
P1, N=84, Recruiting,
Trial completion date: May 2025 --> Jun 2026 | Trial primary completion date: Apr 2025 --> Jun 2026 Not yet recruiting --> Recruiting
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), EBC-129 / A*Star, National Cancer Centre Singapore
Trial primary completion date, Combination therapy, Metastases: A Study of EBC-129 in Advanced Solid Tumours (clinicaltrials.gov) - Apr 13, 2023
P1, N=84, Not yet recruiting,
Clinical trial information: NCT02521844. Trial primary completion date: Mar 2024 --> Apr 2025
- |||||||||| ETC-159 / Experimental Therapeutics Centre, A*Star, National University of Singapore
Journal: ETC-159, an Upstream Wnt inhibitor, Induces Tumour Necrosis via Modulation of Angiogenesis in Osteosarcoma. (Pubmed Central) - Mar 16, 2023
Consistent with our hypothesis, we noted that ETC-159 treatment not only resulted in markedly decreased ?-catenin staining in xenografts, but also increased tumour necrosis and a significant reduction in vascularity-a hereby yet undescribed phenotype following ETC-159 treatment. Through further understanding the mechanism of this new window of vulnerability, therapies can be developed to potentiate and maximize the effectiveness of ETC-159, further increasing its clinical utility for the treatment of OS.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), EBC-129 / A*Star, National Cancer Centre Singapore
Trial primary completion date, Combination therapy, Metastases: A Study of EBC-129 in Advanced Solid Tumours (clinicaltrials.gov) - Mar 8, 2023
P1, N=84, Not yet recruiting,
Through further understanding the mechanism of this new window of vulnerability, therapies can be developed to potentiate and maximize the effectiveness of ETC-159, further increasing its clinical utility for the treatment of OS. Trial primary completion date: Mar 2025 --> Mar 2024
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), EBC-129 / A*Star, National Cancer Centre Singapore
New P1 trial, Combination therapy, Metastases: A Study of EBC-129 in Advanced Solid Tumours (clinicaltrials.gov) - Jan 27, 2023
P1, N=84, Not yet recruiting,
- |||||||||| ETC-159 / Experimental Therapeutics Centre, A*Star, National University of Singapore
Journal: Autocrine canonical Wnt signaling primes noncanonical signaling through ROR1 in metastatic castration-resistant prostate cancer. (Pubmed Central) - Apr 19, 2022
IHC confirmed tumor cell WLS expression in primary prostate cancer and mCRPC, and patient-derived prostate cancer xenografts expressing WLS were responsive to treatment with Wnt synthesis inhibitor ETC-1922159...These findings reveal that Wnt/β-catenin signaling in PC drives stem cell maintenance and invasion and primes for noncanonical Wnt signaling through ROR1. They further show that autocrine Wnt production is a nongenomic driver of canonical and noncanonical Wnt signaling in PC, which can be targeted with Wnt synthesis inhibitors to suppress tumor growth.
- |||||||||| ETC159 / Experimental Therapeutics Centre, WNT974 / Novartis
Journal: Structural model of PORCN illuminates disease-associated variants and drug binding sites. (Pubmed Central) - Feb 3, 2022
Drugs including ETC-159, IWP-L6 and LGK-974 dock in the PORCN catalytic site, providing insights into PORCN pharmacologic inhibition. This structural model enhances our mechanistic understanding of PORCN substrate recognition and catalysis as well as the inhibition of its enzymatic activity and can facilitate the development of improved inhibitors and the understanding of disease relevant PORCN mutants.
- |||||||||| Review, Journal: Recent updates on Wnt signaling modulators: a patent review (2014-2020). (Pubmed Central) - Nov 5, 2021
Antibody based Wnt modulator, OTSA101-DTPA-90Y is currently under Phase I for the treatment of relapsed or refractory synovial sarcoma while OMP-18R5 is under Phase I for metastatic breast cancer. Ongoing preclinical and clinical trials will define the role of the Wnt pathway in different therapeutic areas and have opened new opportunities.
- |||||||||| ETC159 / Experimental Therapeutics Centre, Lynparza (olaparib) / Merck (MSD), AstraZeneca
Journal, BRCA Biomarker, PARP Biomarker: WNT inhibition creates a BRCA-like state in Wnt-addicted cancer. (Pubmed Central) - Oct 27, 2021
In a survey for potential combination therapies, we found that Wnt inhibition synergizes with the PARP inhibitor olaparib in Wnt-addicted cancers...Our findings suggest a general paradigm that Wnt/β-catenin signaling enhances DNA repair in stem cells and cancers to maintain genomic integrity. Conversely, interventions that block Wnt signaling may sensitize cancers to radiation and other DNA damaging agents.
- |||||||||| ETC159 / Experimental Therapeutics Centre
Preclinical, Journal: Amelioration of bone fragility by pulsed electromagnetic fields in type 2 diabetic KK-Ay mice involving Wnt/β-catenin signaling. (Pubmed Central) - Jul 30, 2021
Moreover, PEMF-induced improvement in bone microstructure, mechanical strength, and bone formation in KK-Ay mice was abolished after intragastric administration with the Wnt antagonist ETC-159...Together, our results suggest that PEMF can improve bone microarchitecture and quality by enhancing the biological activities of osteoblasts and osteocytes, which are associated with the activation of the Wnt/β-catenin signaling pathway. PEMF might become an effective countermeasure against T2DM-induced bone deterioration.
- |||||||||| PRI-724 / PRISM Pharma, Ohara Pharma, ETC159 / Experimental Therapeutics Centre, WNT974 / Novartis
Journal: Small-Molecule Inhibitors Targeting the Canonical WNT Signaling Pathway for the Treatment of Cancer. (Pubmed Central) - Jun 22, 2021
Herein we summarize recent progress in the drug discovery and development of small-molecule inhibitors targeting the canonical WNT pathway, focusing on their specific target proteins, in vitro and in vivo activities, physicochemical properties, and therapeutic potential. The relevant opportunities and challenges toward maintaining the balance between efficacy and toxicity in effectively targeting this pathway are also highlighted.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), ETC-159 / Experimental Therapeutics Centre, A*Star, National University of Singapore
Enrollment open, Trial completion date, Combination therapy, Metastases: A Study to Evaluate the Safety and Tolerability of ETC-1922159 as a Single Agent and in Combination With Pembrolizumab in Advanced Solid Tumours (clinicaltrials.gov) - Aug 31, 2020
P1, N=83, Recruiting,
BMRC, NRF and NMRC Singapore. Active, not recruiting --> Recruiting | Trial completion date: Dec 2022 --> Jul 2023
- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS
Sensitizing microsatellite stable colorectal cancer to immune checkpoint therapy utilizing Wnt pathway inhibition (Virtual Meeting II: E-Posters) - May 16, 2020 - Abstract #AACRII2020AACR-II_2732;
Lastly, VECTRA analysis corroborates the flow cytometry data showing a changing tumor immune landscape through an increase in CD4+ and CD8+ T cells in the tumor and surrounding stroma.Our data demonstrates the combination treatment of ETC-159 + nivolumab in MSS CRC hPDX show increased tumor infiltration of human immune cells. Further preclinical data is compulsory but these results support further development of this combination in clinical trials.
- |||||||||| ETC159 / Experimental Therapeutics Centre, pictilisib (GDC-0941) / Roche
Journal: PORCN inhibition synergizes with PI3K/mTOR inhibition in Wnt-addicted cancers. (Pubmed Central) - Feb 28, 2020
This was largely due to enhanced suppressive effects on both cell proliferation and glucose metabolism. These findings demonstrate that dual PORCN and PI3K/mTOR inhibition is a potential strategy for treating Wnt-driven pancreatic cancers.
- |||||||||| ETC159 / Experimental Therapeutics Centre
Journal: Broad regulation of gene isoform expression by Wnt signaling in cancer. (Pubmed Central) - Feb 20, 2020
We used deep time-resolved RNA-seq in two independent in vivo Wnt-addicted tumor models during treatment with the potent Wnt inhibitor ETC-159 and examined Wnt regulated splicing events and splicing regulators...This suggests that the Wnt regulated splicing events are components of fundamental oncogenic processes. These findings demonstrate the wide-ranging effects of Wnt signaling on the isoform composition of the cell and provides an extensive resource of expression changes of splicing regulators and gene isoforms regulated by Wnt signaling. .
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), ETC-159 / Experimental Therapeutics Centre, A*Star, National University of Singapore
Enrollment closed, Trial completion date, Trial primary completion date, Combination therapy, Metastases: A Study to Evaluate the Safety and Tolerability of ETC-1922159 as a Single Agent and in Combination With Pembrolizumab in Advanced Solid Tumours (clinicaltrials.gov) - May 16, 2019
P1, N=65, Active, not recruiting,
These findings demonstrate the wide-ranging effects of Wnt signaling on the isoform composition of the cell and provides an extensive resource of expression changes of splicing regulators and gene isoforms regulated by Wnt signaling. . Recruiting --> Active, not recruiting | Trial completion date: Aug 2018 --> Dec 2022 | Trial primary completion date: Aug 2018 --> Dec 2022
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), ETC-159 / Experimental Therapeutics Centre, A*Star, National University of Singapore
Trial primary completion date, Combination therapy, Metastases: A Study to Evaluate the Safety and Tolerability of ETC-1922159 as a Single Agent and in Combination With Pembrolizumab in Advanced Solid Tumours (clinicaltrials.gov) - Jun 23, 2017
P1, N=65, Recruiting,
Recruiting --> Active, not recruiting | Trial completion date: Aug 2018 --> Dec 2022 | Trial primary completion date: Aug 2018 --> Dec 2022 Trial primary completion date: Apr 2018 --> Aug 2018
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