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

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 Women With HR+ / HER2- Metastatic Breast Cancer and Non-visceral Disease

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

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