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

Status: Active


The main objective of the trial is to assess the anti-tumor activity of xentuzumab in combination with everolimus and exemestane over everolimus and exemestane in post menopausal patients with HR+ / HER2- advanced or metastatic breast cancer and non-visceral disease.

Eligibility Criteria

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

Locations & Contacts


San Francisco
UCSF Medical Center-Mount Zion
Status: Approved
Contact: Helen Diller Family Comprehensive Cancer Center
Phone: 877-827-3222


University of Minnesota / Masonic Cancer Center
Status: Active
Contact: Heather Beckwith
Phone: 612-625-4918

Trial Phase & Type

Trial Phase

Phase II

Trial Type


Lead Organization

Lead Organization
Boehringer Ingelheim Pharmaceuticals Inc

Trial IDs

Primary ID 1280-0022
Secondary IDs NCI-2019-04526, 2017-003131-11 ID NCT03659136