The XENERA™ 1 Study Tests Xentuzumab in Combination With Everolimus and Exemestane in Women With Hormone Receptor Positive and HER2-negative Breast Cancer That Has Spread

Inclusion Criteria: * 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 Exclusion Criteria: * Previous treatment with agents targeting the IGF pathway, AKT, or mTOR pathways * Prior treatment with exemestane (except adjuvant exemestane stopped \>12 months prior to start of study treatment as long as the patient did not recur during or within 12 months after the end of adjuvant exemestane) * Evidence of visceral metastasis/es (i.e. liver, lung, peritoneal, pleural metastases, malignant pleural effusions, malignant peritoneal effusions) at screening. NOTE: Patients with a past history of visceral metastases are eligible if visceral metastases have completely resolved at least 3 months * History or evidence of metastatic disease to the brain * Leptomeningeal carcinomatosis * More than 1 prior line of chemotherapy for HR+ HER2- metastatic breast cancer * Radiotherapy within 4 weeks prior to the start of study treatment * Use of concomitant systemic sex hormone therapy * History or presence of cardiovascular abnormalities * Known pre-existing interstitial lung disease * Further exclusion criteria apply