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

NCT05573126 | Recruiting Phase 1 FDA Drug

• 1 other identifier: EP0062-101
• Study Type: interventional
• Target: 95
• Locations: 3 countries
• Sites: 14

Brief Summary

The aim of this study is to identify the optimal dose for 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

Conditions

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

Outcome Measures

Primary Outcomes (4)

• Incidence of dose-limiting toxicities (DLTs) during Cycle 1 of EP0062 treatment

  Module A

  first 28 days

• Maximum tolerated dose (MTD) and doses for evaluation in the expansion cohorts

  Module A

  1 year

• Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

  Module A/B

  up to 30 days after the end of treatment

• Recommended clinical (dose (s) for combination therapy

  Module B

  1 year

Secondary Outcomes (10)

• Plasma pharmacokinetic (PK) parameters - Half life

  1, 2, 4, 8, 24 and 48 hours during cycle 1

• Plasma pharmacokinetic (PK) parameters - Cmax

  1, 2, 4, 8, 24 and 48 hours during cycle 1

• Plasma pharmacokinetic (PK) parameters - Area under the curve (exposure)

  1, 2, 4, 8, 24 and 48 hours during cycle 1

• Tumour response

  screening and every 8 weeks up to 12 months

• Clinical Benefit Rate (CBR)

  every 8 weeks up to 12 months

Study Arms (4)

Module A - EP0062 Dose Finding

EXPERIMENTAL

Patients are assigned to dose level cohorts to identify optimal dose and assess safety, tolerability and PK profile.

Drug: EP0062

Module B - EP0062+ standard of care targeted therapy (elacestrant).

EXPERIMENTAL

3-6 patients enrolled, with possible expansion up to 25 patients.

Drug: EP0062; Drug: Elacestrant

Module B - EP0062+ standard of care targeted therapy (everolimus/exemestrane)

EXPERIMENTAL

3-6 patients enrolled, with possible expansion up to 25 patients.

Drug: EP0062; Drug: Everolimus; Drug: Exemestane

Module B: EP0062 in combination with Abemaciclib and Fulvestrant

EXPERIMENTAL

3-6 patients enrolled, with possible expansion up to 25 patients.

Drug: EP0062; Drug: Abemaciclib; Drug: Fulvestrant

Interventions

Elacestrant DRUG

Oral SERD

Module B - EP0062+ standard of care targeted therapy (elacestrant).

Everolimus DRUG

mTOR Inhibitor

Module B - EP0062+ standard of care targeted therapy (everolimus/exemestrane)

EP0062 DRUG

EP0062 is an orally administered investigational selective androgen receptor modulator (SARM)

Module A - EP0062 Dose Finding; Module B - EP0062+ standard of care targeted therapy (elacestrant).; Module B - EP0062+ standard of care targeted therapy (everolimus/exemestrane); Module B: EP0062 in combination with Abemaciclib and Fulvestrant

Abemaciclib DRUG

CDK4/6 inhibitor

Module B: EP0062 in combination with Abemaciclib and Fulvestrant

Fulvestrant DRUG

Oral SERD

Module B: EP0062 in combination with Abemaciclib and Fulvestrant

Exemestane DRUG

aromatase inhibitor

Module B - EP0062+ standard of care targeted therapy (everolimus/exemestrane)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women 18 years or older at the time of informed consent
• 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
• 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
• 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
• 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
• Postmenopausal, as defined by at least one of the following:
• Age over 60 years
• 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)
• FSH and oestradiol in the postmenopausal ranges (as per local practice) in women aged \<55 years who have undergone hysterectomy
• Prior bilateral oophorectomy
• Module B arm 1: patients who have progressed on ≤ 2 prior lines of endocrine therapy, including a prior CDK4/6 inhibitor.
• Module B arm 2: patients who have progressed on ≤ 2 prior lines of endocrine therapy in advanced/metastatic setting, including prior CDK4/6 inhibitor
• Module B arm 3: patients who have progressed on treatment with a prior CDK4/6 inhibitor plus an aromatase inhibitor as initial therapy or recurrence on/after treatment with a CDK4/6 inhibitor plus endocrine therapy in the adjuvant setting.

You may not qualify if:

• Patients with any of the following will not be included in the study:
• 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
• Currently taking testosterone, methyltestosterone, oxandrolone, oxymetholone, danazol, fluoxymesterone, testosterone-like agents (e.g., dehydroepiandrosterone, androstenedione, and other androgenic compounds, including herbals), or antiandrogens
• 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
• 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
• 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
• 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
• 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
• Congestive heart failure Grades II-IV according to the New York Heart Association at the time of screening
• Myocardial infarction or unstable angina within the previous 6 months
• 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

Sponsors & Collaborators

• Ellipses Pharma: lead

Study Sites (14)

Yale School of Medicine

New Haven, Connecticut, 06520, United States

COMPLETED

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Henry Ford Hospital

Detroit, Michigan, 48202, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

RECRUITING

Texas Oncology Baylor University Medical Center

Dallas, Texas, 75246, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Hospital 12 de Octubre

Usera, Madrid, 28041, Spain

RECRUITING

Hospital Universitari Vall d'Hebron (VHIO)

Barcelona, 08035, Spain

RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

RECRUITING

NEXT Oncology Hospital Quironsalud

Madrid, 28223, Spain

RECRUITING

Sarah Cannon Research Institute UK

London, London, W1G 6AD, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, Wilmslow Rd, M20 4BX, United Kingdom

RECRUITING

The Clatterbridge Cancer Centre

Liverpool, CH63 4JY, United Kingdom

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

elacestrant; Everolimus; abemaciclib; Fulvestrant; exemestane

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Central Study Contacts

Clinical Trials Team

CONTACT

+44 (0)20 3743 0992; Enquiries@ellipses.life

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2022
• First Posted: October 10, 2022
• Study Start: January 11, 2023
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: March 20, 2026

Record last verified: 2026-03

Locations

US (7); ES (4); GB (3)