RECRUITING

Phase 1/2 Study to Evaluate Vosilasarm (EP0062) as Monotherapy and in Combination in Patients With Advanced or Metastatic AR+/HER-2-/ER+ Breast Cancer

Conditions

Hormone Receptor-positive Breast Cancer Hormone Receptor Positive HER-2 Negative Breast Cancer Metastatic Breast Cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The aim of this study is to identify the optimal dose for Vosilasarm (EP0062) as monotherapy and in combination with standard-of-care therapies to assess its Safety, Tolerability, Pharmacokinetics, and Efficacy in Patients with Relapsed Locally Advanced or Metastatic AR+/HER-2-/ER+ Breast Cancer

Official Title

A Modular, Open-Label, Multi-Centre Phase 1/2 Dose-Finding, Optimisation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of EP0062 as Monotherapy and in Combination in Patients With Relapsed Locally Advanced or Metastatic AR+/HER-2-/ER+ Breast Cancer

Quick Facts

Study Start:2023-01-11

Study Completion:2026-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05573126

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Women 18 years or older at the time of informed consent 2. Histologically proven diagnosis of breast cancer with evidence of metastatic or locally advanced breast adenocarcinoma as defined by the American Joint Committee on Cancer/Union for International Cancer Control/Tumour Node Metastases (AJCC/UICC TNM) staging classification (8th Ed, 2017) and where no conventional therapy is available or considered appropriate by the Investigator or is declined by the patient 3. Availability of archival tumour sample (formalin-fixed, paraffin-embedded block(s) or slides from a primary tumour or biopsy of a metastatic tumour lesion or lesions); in the absence of an archival tumour sample, or if only archival bone tissue is available, a fresh biopsy will need to be collected 4. Biopsy-proven AR+ and ER+ breast cancer * For Module A, AR+ breast cancer is defined as ≥ 10% AR nuclei staining by central immunohistochemistry (IHC) using the Ventana assay * For Modules B and C, AR+ breast cancer is defined as ≥ 30% AR nuclei staining by central IHC using the Ventana assay 5. HER2-negative breast cancer, defined as negative by fluorescence in situ hybridisation (FISH) or IHC score of 0 or 1+. If IHC is equivocal at 2+, a negative FISH test (HER2/Amplification of the centromeric region of chromosome 17)CEP17 ratio of \<2.0) is required 6. Postmenopausal, as defined by at least one of the following: 1. Age over 60 years 2. Amenorrhea \> 12 months at the time of informed consent and an intact uterus, with follicle-stimulating hormone (FSH) and oestradiol in the postmenopausal ranges (as per local practice) 3. FSH and oestradiol in the postmenopausal ranges (as per local practice) in women aged \<55 years who have undergone hysterectomy 4. Prior bilateral oophorectomy 7. Module B arm 1: patients who have progressed on ≤ 2 prior lines of endocrine therapy, including a prior CDK4/6 inhibitor. 8. Module B arm 2: patients who have progressed on ≤ 2 prior lines of endocrine therapy in advanced/metastatic setting, including prior CDK4/6 inhibitor	1. Prior anti-cancer or investigational drug treatment within the following time windows: * Any chemotherapy within 21 days prior to the first dose of study drug * Any non-chemotherapy investigational anti-cancer drug \< 5 half-lives (28 days for biologics) or \< 14 days for small-molecule therapeutics or if half-life is not known * Tamoxifen and aromatase inhibitors within 14 days prior to the first dose of study drug * Fulvestrant or other investigational Selective Estrogen Receptor Degraders (SERDs) within 21 days prior to first dose of study drug 2. Currently taking testosterone, methyltestosterone, oxandrolone, oxymetholone, danazol, fluoxymesterone, testosterone-like agents (e.g., dehydroepiandrosterone, androstenedione, and other androgenic compounds, including herbals), or antiandrogens 3. Radiation therapy within 14 days prior to the first dose of study drug and scheduled to have radiation therapy during participation in this study. Short courses of palliative radiation therapy during the study might be allowed following discussion with and approval by the Medical Monitor. Palliative radiotherapy within 6 weeks prior to first dose of study drug is permitted 4. Unresolved or unstable serious toxic side effects of prior chemotherapy or radiotherapy, i.e., ≥ Grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, except fatigue, alopecia, and Grade 2 chemotherapy-induced neuropathy 5. Confirmed Corrected QT Interval by Fridericia (QTcF) \> 470 ms on screening ECG, or history of torsades de pointes (TdP), or history of congenital long QT syndrome, or immediate family history of long QT syndrome, unexplained sudden death at a young age, or sudden cardiac death 6. Any other clinically important abnormalities in rhythm, conduction, or morphology on resting ECG (e.g., complete left bundle branch block, third-degree heart block); rate-controlled atrial fibrillation is permitted 7. Concomitant medications that prolong the corrected QT interval and/or increase the risk for TdP that cannot be discontinued or substituted with another drug within 5 half-lives or 14 days before the first dose of study drug, whichever is longer 8. Congestive heart failure Grades II-IV according to the New York Heart Association at the time of screening 9. Myocardial infarction or unstable angina within the previous 6 months 10. Patients receiving medications that are known to be strong inhibitors or inducers of CYP3A4 within 5 half-lives or 14 days, whichever is longer, before the first dose of study drug 11. Prior treatment with selected combination agent

Inclusion Criteria

Exclusion Criteria

1. Women 18 years or older at the time of informed consent
2. Histologically proven diagnosis of breast cancer with evidence of metastatic or locally advanced breast adenocarcinoma as defined by the American Joint Committee on Cancer/Union for International Cancer Control/Tumour Node Metastases (AJCC/UICC TNM) staging classification (8th Ed, 2017) and where no conventional therapy is available or considered appropriate by the Investigator or is declined by the patient
3. Availability of archival tumour sample (formalin-fixed, paraffin-embedded block(s) or slides from a primary tumour or biopsy of a metastatic tumour lesion or lesions); in the absence of an archival tumour sample, or if only archival bone tissue is available, a fresh biopsy will need to be collected
4. Biopsy-proven AR+ and ER+ breast cancer
* For Module A, AR+ breast cancer is defined as ≥ 10% AR nuclei staining by central immunohistochemistry (IHC) using the Ventana assay
* For Modules B and C, AR+ breast cancer is defined as ≥ 30% AR nuclei staining by central IHC using the Ventana assay
5. HER2-negative breast cancer, defined as negative by fluorescence in situ hybridisation (FISH) or IHC score of 0 or 1+. If IHC is equivocal at 2+, a negative FISH test (HER2/Amplification of the centromeric region of chromosome 17)CEP17 ratio of \<2.0) is required
6. Postmenopausal, as defined by at least one of the following:
1. Age over 60 years
2. Amenorrhea \> 12 months at the time of informed consent and an intact uterus, with follicle-stimulating hormone (FSH) and oestradiol in the postmenopausal ranges (as per local practice)
3. FSH and oestradiol in the postmenopausal ranges (as per local practice) in women aged \<55 years who have undergone hysterectomy
4. Prior bilateral oophorectomy
7. Module B arm 1: patients who have progressed on ≤ 2 prior lines of endocrine therapy, including a prior CDK4/6 inhibitor.
8. Module B arm 2: patients who have progressed on ≤ 2 prior lines of endocrine therapy in advanced/metastatic setting, including prior CDK4/6 inhibitor

1. Prior anti-cancer or investigational drug treatment within the following time windows:
* Any chemotherapy within 21 days prior to the first dose of study drug
* Any non-chemotherapy investigational anti-cancer drug \< 5 half-lives (28 days for biologics) or \< 14 days for small-molecule therapeutics or if half-life is not known
* Tamoxifen and aromatase inhibitors within 14 days prior to the first dose of study drug
* Fulvestrant or other investigational Selective Estrogen Receptor Degraders (SERDs) within 21 days prior to first dose of study drug
2. Currently taking testosterone, methyltestosterone, oxandrolone, oxymetholone, danazol, fluoxymesterone, testosterone-like agents (e.g., dehydroepiandrosterone, androstenedione, and other androgenic compounds, including herbals), or antiandrogens
3. Radiation therapy within 14 days prior to the first dose of study drug and scheduled to have radiation therapy during participation in this study. Short courses of palliative radiation therapy during the study might be allowed following discussion with and approval by the Medical Monitor. Palliative radiotherapy within 6 weeks prior to first dose of study drug is permitted
4. Unresolved or unstable serious toxic side effects of prior chemotherapy or radiotherapy, i.e., ≥ Grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, except fatigue, alopecia, and Grade 2 chemotherapy-induced neuropathy
5. Confirmed Corrected QT Interval by Fridericia (QTcF) \> 470 ms on screening ECG, or history of torsades de pointes (TdP), or history of congenital long QT syndrome, or immediate family history of long QT syndrome, unexplained sudden death at a young age, or sudden cardiac death
6. Any other clinically important abnormalities in rhythm, conduction, or morphology on resting ECG (e.g., complete left bundle branch block, third-degree heart block); rate-controlled atrial fibrillation is permitted
7. Concomitant medications that prolong the corrected QT interval and/or increase the risk for TdP that cannot be discontinued or substituted with another drug within 5 half-lives or 14 days before the first dose of study drug, whichever is longer
8. Congestive heart failure Grades II-IV according to the New York Heart Association at the time of screening
9. Myocardial infarction or unstable angina within the previous 6 months
10. Patients receiving medications that are known to be strong inhibitors or inducers of CYP3A4 within 5 half-lives or 14 days, whichever is longer, before the first dose of study drug
11. Prior treatment with selected combination agent

Contacts and Locations

Study Contact

Hannah van den Boomen

CONTACT

+44 (0)20 3743 0992

hannah@ellipses.life

Study Locations (Sites)

Yale School of Medicine

New Haven, Connecticut, 06520

United States

Moffitt Cancer Center

Tampa, Florida, 33612

United States

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

Henry Ford Hospital

Detroit, Michigan, 48202

United States

Sarah Cannon Research Institute

Nashville, Tennessee, 37203

United States

Texas Oncology Baylor University Medical Center

Dallas, Texas, 75246

United States

Virginia Cancer Specialists

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: Ellipses Pharma

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-01-11

Study Completion Date2026-11

Study Record Updates

Study Start Date2023-01-11

Study Completion Date2026-11

Terms related to this study

Additional Relevant MeSH Terms

Hormone Receptor-positive Breast Cancer
Hormone Receptor Positive HER-2 Negative Breast Cancer
Metastatic Breast Cancer