Study of MEDI-573 Plus Standard Endocrine Therapy for Women With Hormone-sensitive Metastatic Breast Cancer

An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A serious adverse event (SAE) is an AE that results in death, initial or prolonged inpatient hospitalization, life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or an important medical event. TEAEs and TESAEs are defined as AEs and SAEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurs first (approximately 8 years).

The AEs that occurred during Cycle 1 (Days 1 to 21) and were suspected of having a causal relationship to MEDI-573 and were >= Grade 3 in severity were considered as DLTs.

The AEs that occurred during Cycle 1 (Days 1 to 21) and were suspected of having a causal relationship to MEDI-573 and were >= Grade 3 in severity were considered as DLTs.

Progression-free survival (PFS) was defined as the time from the randomization until the first documentation of disease progression or death due to any cause, whichever occurred first.

The PFS was censored on the date of the last tumor assessment documenting absence of tumor progression for participants who had no documented progression and were still alive prior to data cut-off, dropout, or the initiation of alternate anticancer treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as >= 20% increase in the sum of diameters of target lesions and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of non-target lesions or a new lesion.

An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurs first (approximately 8 years).

An abnormal vital signs that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurs first (approximately 8 years).

An abnormal ECG findings that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurs first (approximately 8 years).

Tumor evaluation was based on RECIST v1.1 by CT or MRI scan as: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new lesions; Stable disease (SD): Neither sufficient shrinkage to qualify as a response nor sufficient growth to qualify as progression; Progressive Disease (PD): >= 20% increase in the sum of diameters of target lesions and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of non-target lesions or a new lesion; not evaluable (NE): either no or only a subset of lesion measurements are made at an assessment.

The ORR was defined as percentage of participants with confirmed complete response or confirmed partial response, where CR was defined as disappearance of all target and non-target lesions and no new lesions and PR was definded as >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions.

Time to response was measured from treatment start to the first documentation of disease response and was evaluated only in participants who achieved objective response (confirmed CR or confirmed PR. The CR was defined as disappearance of all target and non-target lesions and no new lesions and PR was defined as >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions.

Duration of response (DR) is measured from the first documentation of disease response to the first documented progressive disease and was evaluated only in participants who achieved objective response (confirmed CR or confirmed PR). The CR was defined as disappearance of all target and non-target lesions and no new lesions and PR was defined as >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions.

Time to progression was measured from treatment start until the first documentation of disease progression. The PD was defined as >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of non-target lesions or a new lesion.

Overall survival (OS) was measured from treatment start until death.

Mean change in tumor size is reported.

AUC0-day21 of MEDI-573 for Cycle 1 is reported.

AUC0-info of MEDI-573 for Cycle 1 is reported.

DN AUC0-inf of MEDI-573 for Cycle 1 is reported.

Cmax of MEDI-573 for Cycle 1 is reported.

Tmax of MEDI-573 for Cycle 1 is reported.

The CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by AUC(0-infinity).

The elimination half-life (t1/2) is the time measured for the serum concentration of MEDI-573 to decrease by 1 half to its original concentration.

The mean concentration profiles of both IGF-I and IGF-II post administration of MEDI-573 in plasma were evaluated during treatment.

Participants With Positive ADA to MEDI-573 are reported.