The XENERA™-1 Study Tests Xentuzumab in Combination With Everolimus and Exemestane in Post-menopausal 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:

- Progressed during treatment or within 12 months of completion of adjuvant therapy
with an aromatase inhibitor and/or tamoxifen if post-menopausal, or tamoxifen if
pre or peri-menopausal or

- Progressed while on or within 1 month after the end of prior aromatase inhibitor
therapy for advanced/metastatic breast cancer if post-menopausal, or prior
endocrine treatment for advanced/metastatic breast cancer if pre- or
peri-menopausal.

- Patients must not have received more than one previous line of non-steroidal aromatase
inhibitor treatment for advanced/metastatic disease. Prior treatment with one line of
CDK4/6 inhibitors is allowed.

- Prior treatment with fulvestrant if duration was at least 2 years in the adjuvant
setting or at least 6 months in the metastatic setting is allowed.

- Patients must be post-menopausal at time of signature of trial informed consent.

- 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 or mixed (lytic + blastic) bone lesion
according to RECIST version 1.1

- Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.

- Adequate organ function

Exclusion Criteria:

- Previous treatment with agents targeting the IGF pathway, PI3K, 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)

- History or evidence of metastatic disease to the brain

- Leptomeningeal carcinomatosis

- Any previous 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