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ETC-159 In Combination With Pembrolizumab In Advanced MSS/pMMR Ovarian Cancers | Clinical Trials | Clareo Health

RECRUITINGPHASE1

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.

NCT06513624•National University Hospital, Singapore

View on ClinicalTrials.gov

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).

Eligibility

Age

21 - 99 years

Sex

FEMALE

Healthy Volunteers

Inclusion Criteria

•1. Is capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with the protocol requirements.
•2. Is female, and age 21 years or older (Singapore sites) at pre-screening or screening.
•3. Has histologically or cytologically confirmed, advanced or metastatic ovarian cancer with a platinum free interval of less than 6 months from prior platinum based treatment or for whom platinum therapy is no longer an option according to the treating physician
•4. Has MSS/pMMR tumors as determined by immunohistochemistry (IHC), polymerase chain reaction (PCR), or next-generation sequencing (NGS).
•5. Has objective (assessable through clinical signs, symptoms, and/or laboratory findings) and radiologically-confirmed progression of disease at Screening.
•6. Has measurable disease as determined by RECIST v1.1 (Appendix 4, Section 12.4). Target lesions should not be selected in previously irradiated fields unless there is clear evidence of progression.
•7. Has ECOG performance of status 0 to 2 at Screening.
•8. Has life expectancy of at least 3 months at Screening.
•* Absolute neutrophil count ≥1.0 × 109/L
•* Platelet count ≥100 × 109/L (without transfusions within 21 days prior to Day 1 of Cycle 1
+16 more criteria

Exclusion Criteria

•1. Has received anti-cancer therapy including immunotherapy within 4 weeks (28 days) prior to starting study drug or the side effects of such therapy have not resolved to Grade ≤1 within 4 weeks prior to starting study drug or is receiving any concomitant anti-cancer therapy.
•2. Has used other investigational drugs within 4 weeks (28 days) or five half-lives (whichever is longer) prior to the first dose of study drug.
•3. Has evidence of another malignancy not in remission or history of such a malignancy within the last 3 years (except for treated basal or squamous cell carcinoma of the skin, or in situ cancer of the cervix).
•4. Has central nervous system metastases, unless previously treated with surgery, whole-brain radiation or stereotactic radiosurgery, and stable disease for at least 8 weeks without steroid use for at least 4 weeks (28 days) prior to the first dose of ETC-159.
•5. Has received prior radiation therapy within 4 weeks (28 days), or limited field radiation within 2 weeks, prior to starting study drug, or the side effects of such therapy have not resolved to Grade ≤1.
•6. Has any history of direct radiation to spine or pelvis bone or definitive chemoradiation to pelvic organs in the last 6 months prior to starting study drug, or the side effects of such therapy have not resolved to Grade ≤1.
•7. Has a history of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or pulmonary hypersensitivity, or pneumonitis.
•8. Has received bisphosphonate therapy for osteoporosis or symptomatic hypercalcemia or denosumab for osteoporosis within 6 months prior to starting study drug.
•9. Has osteoporosis based on a T-score of \< -2.5 at the left or right total hip, left or right femoral neck, or lumbar spine (L1 to L4) as determined by DEXA scan at Screening (for details of calculating T-score for eligibility see Inclusion Criterion 10).
•10. Has a history of symptomatic vertebral fragility fractures or any fragility fracture of the hip, pelvis, wrist, or other location (a fragility fracture is defined as any fracture without a history of trauma or as a result of a fall from standing height or less).
+34 more criteria

Locations (2)

National Cancer Centre Singapore

Singapore, Singapore, Singapore

National University Hospital

Singapore, Singapore

Key Dates

Start Date

December 9, 2024

Primary Completion Date

December 31, 2026

Completion Date

June 30, 2027

Last Updated

July 25, 2025

Enrollment

ESTIMATED participants

Conditions

With MSS/pMMR Advanced, Platinum-resistant Ovarian Cancer

Interventions

ETC-159

DRUG

Pembrolizumab

DRUG

Denosumab / Zoledronic Acid

DRUG

Contacts

Shao peng David Tan

CONTACT

+65 6908 2222 david_sp_tan@nuhs.edu.sg

Tan

CONTACT