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

NCT06513624 | Recruiting Phase 1

• 1 other identifier: ETC-159-02
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

With MSS/pMMR Advanced, Platinum-resistant Ovarian Cancer

Outcome Measures

Primary Outcomes (2)

• Disease Control Rate (DCR)

  is defined as percentage of subjects with best overall response as (Complete Response (CR) + Partial Response (PR) + Stable disease ≥12 weeks) evaluated by RECIST v1.1 criteria measured by CT or MRI

  1 Year

• Objective Response Rate (ORR)

  is defined as percentage of subjects with best overall response as (Complete Response (CR) + Partial Response (PR)) evaluated by RECIST v1.1 criteria measured by CT or MRI

  1 Year

Study Arms (1)

ETC-159

EXPERIMENTAL

Patients will undergo screening prior to the initial administration of ETC-159 in combination with pembrolizumab. ETC-159 in combination with pembrolizumab will be administered in 21-day cycles. ETC-159 will be dosed every other day while Pembrolizumab will be dosed at IV Q3W along with bone protective treatment (Denosumab or Zoledronic Acid)

Drug: ETC-159; Drug: Pembrolizumab; Drug: Denosumab / Zoledronic Acid

Interventions

ETC-159 DRUG

ETC-159 will be administered orally.

ETC-159

Pembrolizumab DRUG

Pembrolizumab will be administered intravenously.

ETC-159

Denosumab / Zoledronic Acid DRUG

Denosumab will be administrated subcutaneously. Zoledronic Acid will be administered intravenously if denosumab has no response.

ETC-159

Eligibility Criteria

• Age: 21 Years - 99 Years
• Gender Eligibility Details: Is female, and age 21 years or older (Singapore sites) at pre-screening or screening.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with the protocol requirements.
• Is female, and age 21 years or older (Singapore sites) at pre-screening or screening.
• 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
• Has MSS/pMMR tumors as determined by immunohistochemistry (IHC), polymerase chain reaction (PCR), or next-generation sequencing (NGS).
• Has objective (assessable through clinical signs, symptoms, and/or laboratory findings) and radiologically-confirmed progression of disease at Screening.
• 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.
• Has ECOG performance of status 0 to 2 at Screening.
• 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
• Hemoglobin ≥9 g/dL
• Prothrombin time and partial thromboplastin time within ≤1.5 × upper limit of normal (ULN)
• International normalized ratio (INR) ≤1.5 × ULN Note: If the patient is on allowed anti-coagulants the INR and coagulation parameters should be in the therapeutic range
• Total bilirubin ≤1.5 × ULN
• Transaminases (AST and/or alanine aminotransferase ≤2.5 × ULN (\<5 × ULN if liver metastases)

You may not qualify if:

• 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.
• 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.
• 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).
• 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.
• 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.
• 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.
• Has a history of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or pulmonary hypersensitivity, or pneumonitis.
• Has received bisphosphonate therapy for osteoporosis or symptomatic hypercalcemia or denosumab for osteoporosis within 6 months prior to starting study drug.
• 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).
• Has moderate (25% to 40% decrease in the height of any vertebra) or severe (\>40% decrease in the height of any vertebra) morphometric vertebral fractures at Screening.
• Has a β-CTX serum level \>1000 pg/mL in the morning after at least 10 hours of fasting at Screening.
• Note: Patients should begin their treatment with the bone protective treatment (denosumab with a starting dose of 120 mg, administered SC), and continued so as to have a β-CTX serum level ≤1000 pg/mL
• Has thyrotropin level less than LLN at Screening
• Has 25-hydroxy vitamin D levels less than 25 nmol/L (10 ng/mL) at screening. Note: For patients known to have less than 25 nmol/L (10 ng/mL) 25-hydroxy vitamin D value that would otherwise be eligible to participate in the study, a single administration of oral vitamin D3 (cholecalciferol) of 100,000 IU or 2 × 50,000 IU is recommended. After a single large dose of vitamin D3, the 25-hydroxy vitamin D level is expected to return to the required range within 7 to 28 days. After the documentation of 25-hydroxy vitamin D level normalization, maintenance treatment can be started by means of oral administration of 1000 IU/day of vitamin D3 or higher, based on the investigator's clinical judgement. While vitamin D3 (cholecalciferol) is recommended for 25-hydroxy vitamin D level restoration and maintenance, equivalent doses of vitamin D2 (ergocalciferol) can be used if vitamin D3 is not available.
• Has bone metastases at Screening.

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• EDDC (Experimental Drug Development Centre), A*STAR Research Entities: collaborator

Study Sites (2)

National Cancer Centre Singapore

Singapore, Singapore, Singapore 169610, Singapore

NOT YET RECRUITING

National University Hospital

Singapore, Singapore

RECRUITING

Related Publications (2)

• Liu J, Pan S, Hsieh MH, Ng N, Sun F, Wang T, Kasibhatla S, Schuller AG, Li AG, Cheng D, Li J, Tompkins C, Pferdekamper A, Steffy A, Cheng J, Kowal C, Phung V, Guo G, Wang Y, Graham MP, Flynn S, Brenner JC, Li C, Villarroel MC, Schultz PG, Wu X, McNamara P, Sellers WR, Petruzzelli L, Boral AL, Seidel HM, McLaughlin ME, Che J, Carey TE, Vanasse G, Harris JL. Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20224-9. doi: 10.1073/pnas.1314239110. Epub 2013 Nov 25.

  PMID: 24277854 BACKGROUND

• DeVito NC, Sturdivant M, Thievanthiran B, Xiao C, Plebanek MP, Salama AKS, Beasley GM, Holtzhausen A, Novotny-Diermayr V, Strickler JH, Hanks BA. Pharmacological Wnt ligand inhibition overcomes key tumor-mediated resistance pathways to anti-PD-1 immunotherapy. Cell Rep. 2021 May 4;35(5):109071. doi: 10.1016/j.celrep.2021.109071.

  PMID: 33951424 BACKGROUND

MeSH Terms

Interventions

ETC-159; pembrolizumab; Denosumab; Zoledronic Acid

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Shao peng David Tan

CONTACT

+65 6908 2222; david_sp_tan@nuhs.edu.sg

Tan

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will undergo screening procedures to determine eligibility within 28 days prior to the initial administration of ETC-159 in combination with pembrolizumab. ETC-159 in combination with pembrolizumab will be administered in 21-day cycles (1 cycle: 21 days). ETC-159 will be dosed every other day. Pembrolizumab will be dosed IV Q3W. Tumor response assessments will be done every 6 weeks (2 cycles) prior to starting the cycle starting at C3D1 (- 7 days) until C9D1 (- 7 days); thereafter every 12 weeks (4 cycles) starting at C13D1 (- 7 days) and at EOT, until disease progression or start of another anti-cancer therapy according to RECIST v1.1.

Study Record Dates

• First Submitted: July 17, 2024
• First Posted: July 22, 2024
• Study Start: December 9, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

SG (2)