NCT06513624

ETC-159 In Combination With Pembrolizumab In Advanced MSS/pMMR Ovarian Cancers

A Phase 1B Investigator Initiated Study To Evaluate The Preliminary Activity, Safety And Tolerability Of ETC-159 In Combination With Pembrolizumab In Advanced MSS/pMMR Ovarian Cancers.

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (estimated)
• Sponsor: National University Hospital, Singapore · Academic / Other
• Sex: Female
• Age: 21 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label, single-arm, investigator-initiated study conceived as a dose expansion cohort of the study D3-002, which evaluated ETC-159 in combination with pembrolizumab in solid tumors.

Detailed description

Hypothesis: Wnt pathway inhibition with ETC-159 in combination PD1 checkpoint inhibition is safe and effective for the treatment of patients with advanced MSS/pMMR ovarian cancer.It is hypothesized that, ETC-159, as a selective PORCNi, will lead to increased immune infiltration and therefore may turn "cold" tumors into "hot" tumors that may then be responsive to checkpoint inhibitor Primary Objectives: 1. To evaluate the preliminary clinical activity of ETC-159 in combination with pembrolizumab according to RECIST v1.1, in patients with advanced or metastatic, platinum-resistant MSS/pMMR ovarian cancer 2. To assess the safety of ETC-159 at the dose of 8 mg every other day (the recommended dose \[RD\] identified in safety segment) in combination with pembrolizumab. Secondary Objectives: 1. To further assess the efficacy of ETC-159 in combination with pembrolizumab 2. To evaluate the PK of ETC-159 in combination with pembrolizumab in patients. Exploratory Objectives: 1. To evaluate the effect of ETC-159 administered orally every other day in combination with pembrolizumab with bone protective treatment (denosumab and subsequently zoledronic acid if no response is observed with denosumab) on bone turnover markers as potential downstream markers of Wnt signaling (β-CTX). 2. To correlate available tumor genomic profile with clinical data. 3. To evaluate the effect of ETC-159 treatment on : * Pharmacodynamic biomarker (Axin2 mRNA expression levels) in hair follicles. * Gene expression levels and PD-L1 protein expression measured in FFPE-tumor tissue (if sufficient tissue is available). 4. To determine change in serum levels of cancer antigen 125 (CA-125).

Conditions

• With MSS/pMMR Advanced, Platinum-resistant Ovarian Cancer

Interventions

Type	Name	Description
DRUG	ETC-159	ETC-159 will be administered orally.
DRUG	Pembrolizumab	Pembrolizumab will be administered intravenously.
DRUG	Denosumab / Zoledronic Acid	Denosumab will be administrated subcutaneously. Zoledronic Acid will be administered intravenously if denosumab has no response.

Timeline

• Start date: 2024-12-09
• Primary completion: 2026-12-31
• Completion: 2027-06-30
• First posted: 2024-07-22
• Last updated: 2025-07-25

Locations

2 sites across 1 country: Singapore