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
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
• 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