Xenera-1: A 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


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.


Accepting new patients

Primary Study Objective(s)

The primary objective is progression-free survival (PFS) as assessed by central review. Defined as time from randomisation until disease progression according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) or death from any cause, whichever occurs earlier.

Core eligibility

Note: This is only a partial list of eligibility criteria.

Including patients who:

  • Have documented histologically confirmed breast cancer with ER and/ or PgR-positive and HER2-negative status
  • Have locally advanced or metastatic breast cancer not deemed amenable to curative surgery or curative radiation therapy
  • Agree to provide a formalin-fixed paraffin embedded tissue biopsy preferably taken at the time of presentation with recurrent or metastatic disease. Provision of any archival tissue is acceptable, e.g. patients with bone only disease (required) 
  • Satisfy the following criteria for prior therapy (required):
    • Patient 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
    • Patient 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.
  • 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 (allowed)
  • Had prior treatment with fulvestrant if duration was at least two years in the adjuvant setting or at least six months in the advanced/metastatic setting (allowed)
  • Are post-menopausal at time of signature of trial informed consent (required)
  • Have (required):
    • 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
  • Have an Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1
  • Have adequate organ function

Excluding patients who have:

  • Had previous treatment with agents targeting the IGF pathway, PI3K, AKT, or mTOR pathways
  • Had 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
  • Had any previous chemotherapy for metastatic breast cancer
  • Had radiotherapy within four weeks prior to the start of study treatment
  • Had concomitant systemic sex hormone therapy
  • History or presence of cardiovascular abnormalities
  • Known pre-existing interstitial lung disease

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