ETC-159

P1, N=89, Active, not recruiting, EDDC (Experimental Drug Development Centre), A*STAR Research Entities | Recruiting --> Active, not recruiting | Trial completion date: Aug 2024 --> May 2024 | Trial primary completion date: Dec 2022 --> Feb 2024

Six PROC patients were treated with the combination in dose escalation & expansion. The majority (66%) were high- grade serous ovarian carcinomas with a median 4 lines (2-7) of previous treatments. SAEs were pneumonitis and erythema with fever (8 mg, 1 patient).

Consistent with our hypothesis, we noted that ETC-159 treatment not only resulted in markedly decreased β-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.

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.

P1, N=89, Recruiting, EDDC (Experimental Drug Development Centre), A*STAR Research Entities | Trial completion date: Apr 2023 --> Aug 2024

P1, N=83, Recruiting, EDDC (Experimental Drug Development Centre), A*STAR Research Entities | Trial completion date: Jul 2023 --> Apr 2023

This CTA is currently used to pre-screen & select patients for the phase IB trial with the porcupine inhibitor ETC-1922159 (NCT02521844) ongoing in Singapore and USA...Funding: BMRC, NRF and NMRC Singapore. Clinical trial identification: NCT02521844.

This CTA is currently used to pre-screen & select patients for the phase IB trial with the porcupine inhibitor ETC-1922159 (NCT02521844) ongoing in Singapore and USA. BMRC, NRF and NMRC Singapore.

This CTA is currently used to pre-screen & select patients for the phase IB trial with the porcupine inhibitor ETC-1922159 (NCT02521844) ongoing in Singapore and USA. BMRC, NRF and NMRC Singapore.

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.

Furthermore, the combination of the PORCN inhibitor ETC-159 and the pan-PI3K inhibitor GDC-0941 potently suppressed the in vivo growth of RNF43-mutant pancreatic cancer xenografts. 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.