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
Condition: Breast Neoplasms
MeSH terms: Breast Neoplasms
Intervention: Xentuzumab; Placebo; Everolimus; Exemestane
Intervention description: Intravenous infusion; Intravenous infusion; Tablet; Tablet
Intervention MeSH terms: Everolimus; Exemestane
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 103.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

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:

               -  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