Xenera-1: This phase II trial is evaluating a new form of immunotherapy (xentuzumab) to see whether it enhances combination treatment with a chemotherapy drug (Everolimus) and hormone therapy drug (Exemestane) in patients with hormone receptor positive (HR+), HER2- breast cancer that has spread to other parts of the bodyA Multi-centre, Double-blind, Placebo-controlled, Randomised Phase II Trial to Compare Efficacy of Xentuzumab in Combination With Everolimus and Exemestane Versus Everolimus and Exemestane in Post-menopausal Women With HR+ / HER2- Metastatic Breast Cancer and Non-visceral Disease

Inclusion

• Documented histologically confirmed breast cancer with ERand/ or PgR-positive and HER2-negative status
• Locally advanced or metastatic breast cancer not deemed amenable to curative surgery or curative radiation therapy
• Archival tumour sample available at the time of informed consent and provided to the central laboratory around the time of randomisation. Patients must provide a formalin-fixed paraffin embedded (FFPE) tissue biopsy sample preferably taken at the time of presentation with recurrent or metastatic disease (provision of a biopsy sample taken from the bone is not acceptable).

• Patients must satisfy the following criteria for prior therapy:

  • Disease progression during treatment or within 12 months of completion of endocrine adjuvant therapy or
  • Disease progression while on or within 1 month after the end of prior endocrine therapy for advanced/metastatic breast cancer (Note: the endocrine therapy does not have to be the treatment immediately prior to trial entry).

• Patients must have

  • At least one measurable non-visceral lesion according to RECIST version 1.1 in either lymph nodes, soft tissue, skin and/or
  • At least one measurable non-visceral lesion according to RECIST version 1.1 as lytic or mixed (lytic + blastic) in bone and/or
  • At least one non-measurable (lytic, mixed lytic + blastic, or blastic) bone lesion according to RECIST version 1.1
• Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
• Fasting glucose <8.9 mmol/L (<160 mg/dL) and HbA1c <8.0%
• Adequate organ function