The XENERAâ„¢ 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