Trial Outcomes & Findings for Study of MEDI-573 Plus Standard Endocrine Therapy for Women With Hormone-sensitive Metastatic Breast Cancer (NCT NCT01446159)

Last Updated: 2020-06-02

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

188 participants

Primary outcome timeframe

From the start of study treatment (Day 1) through 60 days after the last dose of treatment or until the participants started another anticancer therapy, whichever occurs first (approximately 8 years)

Results posted on

2020-06-02

Participant Flow

The study was conducted across 10 countries (Belgium, Canada, France, Germany, Hungary, Israel, Spain, Poland, United Kingdom, USA).

A total of 187 participants were screened in the study. Of which, 183 participants were treated with study drugs.

Participant milestones

Participant milestones
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Overall Study STARTED	3	3	92	85
Overall Study COMPLETED	0	0	21	23
Overall Study NOT COMPLETED	3	3	71	62

Reasons for withdrawal

Reasons for withdrawal
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Overall Study Withdrawal by Subject	1	0	14	11
Overall Study Lost to Follow-up	0	0	1	2
Overall Study Death	2	3	43	36
Overall Study Other	0	0	13	13

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=3 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=3 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI n=92 Participants Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor n=85 Participants Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	Total n=183 Participants Total of all reporting groups
Age, Continuous	66.3 Years STANDARD_DEVIATION 12.3 • n=5 Participants	61.0 Years STANDARD_DEVIATION 8.7 • n=7 Participants	63.2 Years STANDARD_DEVIATION 10.5 • n=5 Participants	63.3 Years STANDARD_DEVIATION 11.0 • n=4 Participants	63.2 Years STANDARD_DEVIATION 10.7 • n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	92 Participants n=5 Participants	85 Participants n=4 Participants	183 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	7 Participants n=5 Participants	6 Participants n=4 Participants	13 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	85 Participants n=5 Participants	79 Participants n=4 Participants	170 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants	1 Participants n=4 Participants	8 Participants n=21 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	3 Participants n=7 Participants	84 Participants n=5 Participants	82 Participants n=4 Participants	171 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants

PRIMARY outcome

Timeframe: From the start of study treatment (Day 1) through 60 days after the last dose of treatment or until the participants started another anticancer therapy, whichever occurs first (approximately 8 years)

Population: Safety population included all participants who received any study therapy and were analyzed per the treatment they actually received.

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=3 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=3 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI n=92 Participants Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor n=85 Participants Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 1b and Phase 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Any TEAEs	3 Participants	3 Participants	90 Participants	82 Participants
Phase 1b and Phase 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Any TESAEs	2 Participants	0 Participants	21 Participants	16 Participants

PRIMARY outcome

Timeframe: Up to Day 21 of Cycle 1

Population: Evaluable population included all participants in Phase 1b of the study, who received at least 1 full cycle of MEDI-573 and completed the safety follow-up through the DLT evaluation period (Days 1 to 21 of Cycle 1).

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.

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=3 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=3 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI n=3 Participants Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)	0 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Up to Day 21 of Cycle 1

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.

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=3 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=3 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI n=3 Participants Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 1b: Number of DLTs	0 DLT events	0 DLT events	0 DLT events	—

PRIMARY outcome

Timeframe: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)

Population: The ITT population included all participants who received any study therapy and were analyzed per their randomized treatment group. Participants enrolled in Phase 2 of the study were analyzed.

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.

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=89 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=85 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 2: Progression-free Survival (PFS)	12.65 Months Interval 8.15 to 15.54	11.33 Months Interval 8.54 to 15.54	—	—

SECONDARY outcome

Population: Safety population included all participants who received any study therapy and were analyzed per the treatment they actually received.

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).

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=3 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=3 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI n=92 Participants Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor n=85 Participants Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood potassium decreased	0 Participants	0 Participants	1 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood uric acid increased	0 Participants	0 Participants	3 Participants	1 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Gamma-glutamyl transferase decreased	0 Participants	1 Participants	0 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Gamma-glutamyl transferase increased	1 Participants	1 Participants	9 Participants	4 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Neutrophilia	0 Participants	0 Participants	1 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Neutrophil count decreased	0 Participants	0 Participants	2 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Anemia	1 Participants	1 Participants	17 Participants	10 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Eosinophilia	0 Participants	0 Participants	1 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Leukopenia	0 Participants	0 Participants	0 Participants	3 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Lymphopenia	0 Participants	0 Participants	1 Participants	2 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Neutropenia	1 Participants	1 Participants	3 Participants	4 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Pancytopenia	0 Participants	0 Participants	0 Participants	1 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Thrombocytopenia	0 Participants	2 Participants	1 Participants	3 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Granulocyte count decreased	0 Participants	1 Participants	0 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Hemoglobin decreased	0 Participants	1 Participants	1 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Lymphocyte count decreased	0 Participants	0 Participants	2 Participants	1 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood chloride decreased	0 Participants	0 Participants	1 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Monocyte count decreased	0 Participants	0 Participants	1 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Neutrophil count increased	0 Participants	0 Participants	1 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Platelet count decreased	0 Participants	0 Participants	4 Participants	1 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs White blood cell count decreased	0 Participants	0 Participants	2 Participants	1 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Alanine aminotransferase increased	2 Participants	0 Participants	8 Participants	4 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Aspartate aminotransferase increased	2 Participants	1 Participants	6 Participants	4 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood albumin decreased	0 Participants	0 Participants	1 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood albumin increased	0 Participants	1 Participants	0 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood alkaline phosphatase increased	0 Participants	1 Participants	5 Participants	5 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood bicarbonate decreased	0 Participants	0 Participants	1 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood bilirubin increased	0 Participants	0 Participants	0 Participants	1 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood creatine increased	0 Participants	1 Participants	1 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood creatinine decreased	0 Participants	0 Participants	0 Participants	1 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood creatinine increased	0 Participants	1 Participants	8 Participants	2 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood glucose increased	0 Participants	0 Participants	1 Participants	1 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood lactate dehydrogenase increased	0 Participants	0 Participants	1 Participants	1 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood magnesium decreased	0 Participants	1 Participants	0 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood sodium decreased	0 Participants	1 Participants	0 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood triglycerides increased	0 Participants	0 Participants	1 Participants	2 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Blood urea increased	0 Participants	0 Participants	1 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Protein total decreased	0 Participants	1 Participants	0 Participants	1 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs Leukocytosis	0 Participants	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Population: Safety population included all participants who received any study therapy and were analyzed per the treatment they actually received.

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).

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=3 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=3 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI n=92 Participants Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor n=85 Participants Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 1b and Phase 2: Number of Participants With Abnormal Vital Signs Reported as TEAEs Bradycardia	1 Participants	0 Participants	1 Participants	1 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Vital Signs Reported as TEAEs Dyspnoea	2 Participants	0 Participants	18 Participants	14 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Vital Signs Reported as TEAEs Orthostatic hypotension	0 Participants	0 Participants	1 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Vital Signs Reported as TEAEs Palpitations	1 Participants	0 Participants	1 Participants	2 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Vital Signs Reported as TEAEs Pyrexia	0 Participants	0 Participants	10 Participants	6 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Vital Signs Reported as TEAEs Temperature intolerance	0 Participants	0 Participants	1 Participants	1 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Vital Signs Reported as TEAEs Body temperature increased	0 Participants	0 Participants	1 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Vital Signs Reported as TEAEs Aspiration	0 Participants	0 Participants	1 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Vital Signs Reported as TEAEs Hypertension	0 Participants	0 Participants	8 Participants	13 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Vital Signs Reported as TEAEs Hypotension	1 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Population: Safety population included all participants who received any study therapy and were analyzed per the treatment they actually received.

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).

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=3 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=3 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI n=92 Participants Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor n=85 Participants Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Atrial fibrillation	0 Participants	0 Participants	1 Participants	2 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Atrial flutter	0 Participants	0 Participants	0 Participants	1 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Cardiac valve disease	0 Participants	0 Participants	1 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Palpitation	1 Participants	0 Participants	1 Participants	2 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Arrhythmia	0 Participants	0 Participants	0 Participants	1 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Sinus bradycardia	1 Participants	0 Participants	2 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Sinus tachycardia	0 Participants	0 Participants	0 Participants	1 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Supraventricular tachycardia	0 Participants	0 Participants	0 Participants	2 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Tachycardia	0 Participants	0 Participants	1 Participants	2 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Angina pectoris	0 Participants	0 Participants	0 Participants	1 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Atrioventricular block first degree	0 Participants	0 Participants	1 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Bradycardia	1 Participants	0 Participants	1 Participants	1 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Cardiac failure	0 Participants	0 Participants	1 Participants	0 Participants
Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs Ventricular extrasystoles	0 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From Day 1 until disease progression or death due to any cause, whichever occurred 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.

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=89 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=85 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 2: Number of Participants With Best Overall Tumor Response CR	1 Participants	2 Participants	—	—
Phase 2: Number of Participants With Best Overall Tumor Response SD	48 Participants	46 Participants	—	—
Phase 2: Number of Participants With Best Overall Tumor Response PR	23 Participants	21 Participants	—	—
Phase 2: Number of Participants With Best Overall Tumor Response PD	15 Participants	12 Participants	—	—
Phase 2: Number of Participants With Best Overall Tumor Response NE	2 Participants	4 Participants	—	—

SECONDARY outcome

Timeframe: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)

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.

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=89 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=85 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 2: Objective Response Rate (ORR)	27.0 Percentage of participants Interval 18.1 to 37.4	27.1 Percentage of participants Interval 18.0 to 37.8	—	—

SECONDARY outcome

Timeframe: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)

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.

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=89 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=85 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 2: Time to Response	4.22 Months Interval 1.7 to 18.0	3.98 Months Interval 1.9 to 16.8	—	—

SECONDARY outcome

Timeframe: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)

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.

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=89 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=85 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 2: Duration of Response (DR)	14.55 Months Interval 4.5 to 58.8	17.18 Months Interval 2.1 to 45.1	—	—

SECONDARY outcome

Timeframe: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)

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.

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=89 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=85 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 2: Time to Progression (TTP)	14.39 Months Interval 8.34 to 18.69	11.33 Months Interval 8.54 to 17.97	—	—

SECONDARY outcome

Timeframe: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)

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

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=89 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=85 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 2: Overall Survival (OS)	39.39 Months Interval 0.3 to 73.2	38.34 Months Interval 0.3 to 51.6	—	—

SECONDARY outcome

Timeframe: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)

Mean change in tumor size is reported.

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=89 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=85 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 2: Change in Tumor Size	-36.2 Centimeters Standard Deviation 35.8	-26.8 Centimeters Standard Deviation 37.2	—	—

SECONDARY outcome

Timeframe: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)

Population: The ITT population was considered for this analysis. Participants who received MEDI-573 were analyzed.

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

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=3 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=3 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI n=92 Participants Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 1b and Phase 2: Area Under the Serum Concentration-time Curve From Time Zero to Day 21 (AUC0-day21) of MEDI-573 for Cycle 1	1430 μg·day/mL Standard Deviation 867	4500 μg·day/mL Standard Deviation 725	7990 μg·day/mL Standard Deviation 1590	—

SECONDARY outcome

Timeframe: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)

Population: The ITT population was considered for this analysis. Participants who received MEDI-573 were analyzed.

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

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=3 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=3 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI n=92 Participants Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 1b and Phase 2: Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI-573 for Cycle 1	1500 μg·day/mL Standard Deviation 955	4930 μg·day/mL Standard Deviation 691	9570 μg·day/mL Standard Deviation 2310	—

SECONDARY outcome

Timeframe: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)

Population: The ITT population was considered for this analysis. Participants who received MEDI-573 were analyzed.

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

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=3 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=3 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI n=92 Participants Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 1b and Phase 2: Dose-Normalised Area Under the Serum Concentration-time Curve From Time Zero to Infinity (DN AUC0-inf) of MEDI-573 for Cycle 1	150 day·kg·μg/mL/mg Standard Deviation 95.5	164 day·kg·μg/mL/mg Standard Deviation 23.0	213 day·kg·μg/mL/mg Standard Deviation 51.3	—

SECONDARY outcome

Timeframe: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)

Population: The ITT population was considered for this analysis. Participants who received MEDI-573 were analyzed.

Cmax of MEDI-573 for Cycle 1 is reported.

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=3 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=3 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI n=92 Participants Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 1b and Phase 2: Maximum Observed Serum Concentration (Cmax) of MEDI-573 for Cycle 1	269 μg/mL Standard Deviation 74.1	624 μg/mL Standard Deviation 210	1070 μg/mL Standard Deviation 253	—

SECONDARY outcome

Timeframe: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)

Population: The ITT population was considered for this analysis. Participants who received MEDI-573 were analyzed.

Tmax of MEDI-573 for Cycle 1 is reported.

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=3 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=3 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI n=92 Participants Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 1b and Phase 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-573 for Cycle 1	0.04 Day Interval 0.0 to 0.09	0.07 Day Interval 0.06 to 0.08	0.07 Day Interval 0.03 to 0.17	—

SECONDARY outcome

Timeframe: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)

Population: The ITT population was considered for this analysis. Participants who received MEDI-573 were analyzed.

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).

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=3 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=3 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI n=92 Participants Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 1b and Phase 2: Systemic Clearance (CL) of MEDI-573 for Cycle 1	8.29 mL/day/kg Standard Deviation 3.86	6.17 mL/day/kg Standard Deviation 0.889	4.96 mL/day/kg Standard Deviation 1.13	—

SECONDARY outcome

Timeframe: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)

Population: The ITT population was considered for this analysis. Participants who received MEDI-573 were analyzed.

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.

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=3 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=3 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI n=92 Participants Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 1b and Phase 2: Terminal Half Life (t1/2) of MEDI-573 for Cycle 1	4.38 Day Standard Deviation 1.07	5.91 Day Standard Deviation 2.09	8.45 Day Standard Deviation 2.23	—

SECONDARY outcome

Timeframe: Baseline (Cycle1 Day1 pre-dose), end of treatment (EOT), and 60 days post last dose (Approximately 8 years)

Population: Safety population included all participants who received any study therapy and were analyzed per the treatment they actually received. Participants with free IGF concentration were analyzed.

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

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=3 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=3 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI n=92 Participants Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor n=85 Participants Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 1b and Phase 2: Concentration of Insulin-like Growth Factor (IGF) I and IGF-II Baseline: Free IGF-I Concentration	2.57 ng/mL Standard Deviation 0.712	1.25 ng/mL Standard Deviation 0.635	3.49 ng/mL Standard Deviation 4.39	1.89 ng/mL Standard Deviation 1.24
Phase 1b and Phase 2: Concentration of Insulin-like Growth Factor (IGF) I and IGF-II Baseline: Free IGF-II Concentration	3.81 ng/mL Standard Deviation 1.66	3.07 ng/mL Standard Deviation 0.709	3.01 ng/mL Standard Deviation 1.20	3.03 ng/mL Standard Deviation 1.12
Phase 1b and Phase 2: Concentration of Insulin-like Growth Factor (IGF) I and IGF-II EOT: Free IGF-I Concentration	0.724 ng/mL Standard Deviation 0.421	0.313 ng/mL Standard Deviation 0.0	0.346 ng/mL Standard Deviation 0.130	2.32 ng/mL Standard Deviation 3.64
Phase 1b and Phase 2: Concentration of Insulin-like Growth Factor (IGF) I and IGF-II EOT: Free IGF-II Concentration	0.625 ng/mL Standard Deviation 0.0	0.625 ng/mL Standard Deviation 0.0	0.641 ng/mL Standard Deviation 0.102	3.12 ng/mL Standard Deviation 1.22
Phase 1b and Phase 2: Concentration of Insulin-like Growth Factor (IGF) I and IGF-II 60 days post last dose: Free IGF-I Concentration	1.54 ng/mL Standard Deviation NA Not applicable as only one participant was evaluable for the specified time point.	1.33 ng/mL Standard Deviation 0.3	1.02 ng/mL Standard Deviation 1.29	4.62 ng/mL Standard Deviation 8.52
Phase 1b and Phase 2: Concentration of Insulin-like Growth Factor (IGF) I and IGF-II 60 days post last dose: Free IGF-II Concentration	1.49 ng/mL Standard Deviation NA Not applicable as only one participant was evaluable for the specified time point.	0.625 ng/mL Standard Deviation 0.0	0.984 ng/mL Standard Deviation 0.734	3.38 ng/mL Standard Deviation 1.51

SECONDARY outcome

Timeframe: Pre-infusion on Day 1 of each cycle, End of Treatment, Day 30, 60 and 90 post treatment (approximately 8 years)

Population: Participants who received MEDI-573 and were analyzed per the treatment they actually received were analyzed for this outcome measure.

Participants With Positive ADA to MEDI-573 are reported.

Outcome measures

Outcome measures
Measure	MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) n=3 Participants Participants enrolled in Phase 1b of the study and received intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 30 mg/kg + AI n=3 Participants Participants enrolled in Phase 1 b of the study and received intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.	MEDI-573 45 mg/kg + AI n=92 Participants Participants received intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons. Three participants were enrolled in Phase 1b and 89 were enrolled in Phase 2 of the study.	Aromatase Inhibitor Participants enrolled in Phase 2 of the study and received oral AI (letrozole, anastrozole, or exemestane) once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Phase 1b and Phase 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI-573	0 Participants	0 Participants	1 Participants	—

Adverse Events

MEDI-573 10 mg/kg + Aromatase Inhibitor (AI)

Serious events: 2 serious events

Other events: 3 other events

Deaths: 2 deaths

MEDI-573 30 mg/kg + AI

Serious events: 0 serious events

Other events: 3 other events

Deaths: 3 deaths

MEDI-573 45 mg/kg + AI

Serious events: 21 serious events

Other events: 86 other events

Deaths: 43 deaths

Aromatase Inhibitor

Serious events: 16 serious events

Other events: 79 other events

Deaths: 36 deaths

Serious adverse events

Other adverse events

Additional Information

Shahram Rahimian

MedImmune, LLC

Phone: +1-800-236-9933

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee MedImmune has 60 days to review results communications prior to public release and may delete information that compromises on-going studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
Publication restrictions are in place

Restriction type: OTHER