Phase 1/2 Study to Evaluate EP0062 in Patients With Relapsed Locally Advanced or Metastatic Androgen Receptor Positive (AR+)/HER2-/ER+ Breast Cancer

Inclusion Criteria:

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

Exclusion Criteria:

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