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

Boehringer Ingelheim

Status and phase: Completed; Phase 2

Conditions: Breast Neoplasms

Treatments: Drug: Exemestane; Drug: Everolimus; Drug: Xentuzumab; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03659136

2017-003131-11 (EudraCT Number)

1280-0022

Details and patient eligibility

About

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.

Enrollment: 103 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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103 participants in 2 patient groups, including a placebo group

Xentuzumab/everolimus/exemestane

Experimental group

Treatment:

Drug: Xentuzumab

Drug: Everolimus

Drug: Exemestane

Placebo/everolimus/exemestane

Placebo Comparator group

Treatment:

Drug: Placebo

Drug: Everolimus

Drug: Exemestane