Cancer
Conditions
Brief summary
Evaluate the safety and tolerability of MEDI-573 in adult subjects with advanced solid tumors refractory to standard therapy or for which no standard therapy exists.
Interventions
DRUGMEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
Sponsors
MedImmune LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed advanced solid tumor for which no curative or standard therapies exist. * Karnofsky Performance Status ≥60. * Adequate hematological function. * Adequate organ function. * Women of non-child-bearing potential (defined as being \>1 year post-menopausal) or using effective contraception, e.g., use of oral contraceptives with an additional barrier method (since the investigational product may impair the effectiveness of oral contraceptives), double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy, or total abstinence, from the time the informed consent is signed through 30 days after the last dose of MEDI-573. Male subjects with partners of child-bearing potential must be surgically sterile or use contraceptive method as described above from the time of the initiation of MEDI-573 through 30 days after the last dose of MEDI-573.
Exclusion criteria
* No prior treatment within 4 weeks of study drug administration. * No concurrent therapy for treatment of cancer. * No uncontrolled diabetes. * New York Heart Association Grade ≥ 2 congestive heart failure. * History of myocardial infarction, unstable angina, transient ischemic attack or stroke within the previous 6 months prior to study entry. * Documented brain metastasis. * Pregnancy or lactation or plans to become pregnant while on study. * Clinically significant abnormality on ECG.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years | AEs were any unfavorable and unintended signs (including abnormal laboratory findings), symptoms, or diseases temporally associated with the use of MEDI-573, whether or not considered related to MEDI-573. A SAE was any AE that resulted in: death; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; was life-threatening; was a congenital anomaly/birth defect in the offspring of a study participant; or was an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes above. TEAEs were defined as AEs present at baseline that worsened in intensity after administration of MEDI-573, or events absent at baseline that emerged after administration of MEDI-573, up to 30 days after the last dose. |
| Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years | An abnormal laboratory finding that was judged by the investigator to be medically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-573, or events absent at baseline that emerged after administration of MEDI-573, for the period extending to 30 days after the last dose. |
| Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years | Vital signs and physical findings included parameters such as heart rate, blood pressure, temperature, and respiratory rate. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-573 or events absent at baseline that emerged after administration of MEDI-573, for the period extending to 30 days after the last dose. |
| Maximum Tolerated Dose (MTD) of MEDI-573 | Cycle 1 Day 1 through Cycle 1 Day 21 | The MTD was defined as the highest dose that can be safely administered to participants and was determined by the number of participants in each cohort with a dose-limiting toxicity (DLT). The number and proportion of participants in each dose cohort and the number of participants with a DLT was presented using the total number of participants in the MTD Evaluable Population as the denominator. 2 participants from Cohorts 0.5 and 5 mg/kg QWk (1 in each cohort) did not complete the DLT period and therefore not evaluable for MTD. |
| Number of Participants With Dose-Limiting Toxicities (DLTs) | Cycle 1 Day 1 through Cycle 1 Day 21 | A DLT was defined as any grade greater than or equal to (\>=) 3 treatment-related non-hematologic toxicity that occurred during the DLT assessment period with the following exceptions: Grade less than (\<) 4 serum-high glucose (fasting) with duration of \< 24 hours; Grade 3 fever (in the absence of neutropenia) defined as \> 40.0 degree centigrade (°C) \[greater than (\>) 104.0°F\] that resolved to normal or baseline within 24 hours of treatment and was not considered an SAE; or Grade 3 rigors/chills that responded to optimal therapy; any Grade \>= 3 treatment-related hematologic toxicity that occurred during the DLT assessment period. |
| Optimal Biologically Effective Dose (OBED) of MEDI-573 | From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years | The OBED was defined as the dose at which all circulating insulin-like growth factor (IGF)-1 and IGF-2 ligand was sequestered by MEDI-573. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI-573 | Pre-infusion on Day 1 of each cycle, end of treatment, and 90 days after last dose MEDI-573 (up to 3.5 years) | Two methods were used to assess the immunogenicity data: an ECL-based method and measurement of neutralizing ADA. The titer was calculated by multiplying the minimum assay dilution factor by the reciprocal of the highest dilution factor which yielded an ECL multiple equal to or greater than the screening assay cut-point factor. |
| Objective Response Rate (ORR) | From study entry through the end of the study, up to 3.5 years | The ORR was defined as the proportion of participants with confirmed complete response (CR) or partial response (PR) according to the RECIST criteria The CR was defined as disappearance of all target and nontarget lesions and no new lesions; and PR was definded as \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline \[screening\]) and no new lesions. |
| Progression-free Survival (PFS) | From study entry through the end of the study, up to 3.5 years | Progression-free survival (PFS) was defined as the duration from the start of treatment with MEDI-573 until the documentation of disease progression or death due to any cause, whichever occurred first. |
| Time to Progression | From study entry through the end of the study, up to 3.5 years | Time to disease progression (TTP) was defined as the duration from the start of treatment with MEDI-573 until the documentation of disease progression. |
| Maximum Observed Serum Concentration (Cmax) After the First Dose | For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15 | The Cmax was the maximum observed serum concentration of MEDI-573. |
| Time to Response (TTR) | From study entry through the end of the study, up to 3.5 years | Time to response was defined as the duration from the start of treatment with MEDI-573 to the first documentation of objective response (confirmed CR or PR) and was only assessed in participants who had achieved objective response. |
| Duration of Response | From study entry through the end of the study, up to 3.5 years | Duration of response was defined as the duration from the first documentation of objective response (confirmed CR or PR) to the first documented disease progression. |
| Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years | The suppression profiles of both IGF-1 and IGF-2 post administration of MEDI-573 in relation to time course of antibody concentrations in serum were evaluated during treatment. |
| Overall Survival | From study entry through the end of the study, up to 3.5 years | Overall survival (OS) was defined as the time from the start of treatment with MEDI-573 until death. |
| Time to Reach Maximum Observed Concentration (Tmax) After the First Dose | For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15 | The tmax was defined as actual sampling time to reach the maximum observed serum concentration of MEDI-573. |
| Trough Serum Concentration (Ctrough) After the First Dose | For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15 | The Ctrough was the lowest serum concentration of MEDI-573 within a dosing interval. |
| Dose Normalized Cmax (Cmax/Dose) After the First Dose | For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15 | The Cmax/dose was the dose-normalized maximum serum concentration of MEDI-573. |
| Area Under the Serum Concentration-time Curve Over the First Dosing Interval (AUCτ) | For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15 | Area under the serum concentration-time curve over the first dosing interval. |
| Dose-normalized Area Under the Serum Concentration Time Curve Over the First Dosing Interval (AUCτ/Dose) | For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15 | The AUCtau/dose was a measure of dose-normalized area under the serum concentration-time curve over the first dosing interval. |
Countries
United States
Participant flow
Recruitment details
A total of 43 participants ((23 participants in dose-escalation phase and 20 participants in dose-expansion phase) were entered in the study and received the study treatment.
Participants by arm
| Arm | Count |
|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation Participants received MEDI-573 0.5 milligram per kilogram (mg/kg) as a 60-minute intravenous (IV) infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal. | 4 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation Participants received MEDI-573 1.5 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal. | 3 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion Participants received MEDI-573 5 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal. | 14 |
| MEDI-573 10 mg/Kg QWk Dose Escalation Participants received MEDI-573 10 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal. | 3 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion Participants received MEDI-573 15 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal. | 13 |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation Participants received MEDI-573 30 mg/kg as a 90-minute IV infusion once every 21 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal. | 3 |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation Participants received MEDI-573 45 mg/kg as a 90-minute IV infusion once every 21 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal. | 3 |
| TOTAL Total of all reporting groups | 43 |
| Total | 86 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 4 | 3 | 3 | 3 | 1 | 1 | 3 | 7 | 8 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation | TOTAL |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 53.8 Years STANDARD_DEVIATION 12.2 | 67.0 Years STANDARD_DEVIATION 8.7 | 64.5 Years STANDARD_DEVIATION 13.7 | 68.0 Years STANDARD_DEVIATION 13.2 | 61.2 Years STANDARD_DEVIATION 8.6 | 58.3 Years STANDARD_DEVIATION 18.5 | 65.7 Years STANDARD_DEVIATION 4.5 | 62.6 Years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 3 Participants | 14 Participants | 3 Participants | 12 Participants | 3 Participants | 3 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 3 Participants | 14 Participants | 3 Participants | 10 Participants | 3 Participants | 2 Participants | 39 Participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 4 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 18 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 10 Participants | 1 Participants | 10 Participants | 1 Participants | 1 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 4 | 3 / 3 | 10 / 14 | 3 / 3 | 9 / 13 | 1 / 3 | 3 / 3 |
| other Total, other adverse events | 4 / 4 | 3 / 3 | 13 / 14 | 3 / 3 | 13 / 13 | 3 / 3 | 3 / 3 |
| serious Total, serious adverse events | 2 / 4 | 1 / 3 | 4 / 14 | 1 / 3 | 6 / 13 | 0 / 3 | 3 / 3 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of MEDI-573
The MTD was defined as the highest dose that can be safely administered to participants and was determined by the number of participants in each cohort with a dose-limiting toxicity (DLT). The number and proportion of participants in each dose cohort and the number of participants with a DLT was presented using the total number of participants in the MTD Evaluable Population as the denominator. 2 participants from Cohorts 0.5 and 5 mg/kg QWk (1 in each cohort) did not complete the DLT period and therefore not evaluable for MTD.
Time frame: Cycle 1 Day 1 through Cycle 1 Day 21
Population: MTD Evaluable Population included all participants in dose-escalation phase who had received at least 1 full cycle of MEDI-573 and completed safety follow-up through DLT period (Cycle 1 Day 1 through Cycle 1 Day 21), or who experienced a DLT. Two participants did not receive a full cycle of MEDI-573 and therefore excluded from MTD population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Maximum Tolerated Dose (MTD) of MEDI-573 | NA mg/kg |
Primary
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
An abnormal laboratory finding that was judged by the investigator to be medically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-573, or events absent at baseline that emerged after administration of MEDI-573, for the period extending to 30 days after the last dose.
Time frame: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
Population: The Safety Population included all participants who had received any MEDI-573 treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Protein total increased | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lipase increased | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Electrocardiogram QT prolonged | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Heart rate increased | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood insulin increased | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Weight decreased | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hematuria | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Weight increased | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 1 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatine increased | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood growth hormone increased | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Glomerular filtration rate decreased | 1 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 1 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | White blood cell count increased | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood bilirubin increased | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | White blood cell count decreased | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Red blood cell count decreased | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood lactate dehydrogenase increased | 1 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Renal failure | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphopenia | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Leukopenia | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Breath sounds abnormal | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thrombocytopenia | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Anemia | 2 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Cardiac enzymes increased | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Anemia | 1 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lipase increased | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | White blood cell count increased | 1 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Heart rate increased | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Leukopenia | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Electrocardiogram QT prolonged | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hematuria | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Cardiac enzymes increased | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Glomerular filtration rate decreased | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood bilirubin increased | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood insulin increased | 1 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Renal failure | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | White blood cell count decreased | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Weight increased | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Protein total increased | 1 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Red blood cell count decreased | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Breath sounds abnormal | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatine increased | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Weight decreased | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thrombocytopenia | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 1 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood lactate dehydrogenase increased | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood growth hormone increased | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphopenia | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Breath sounds abnormal | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Weight decreased | 1 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood insulin increased | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatine increased | 2 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood growth hormone increased | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood bilirubin increased | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood lactate dehydrogenase increased | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Cardiac enzymes increased | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Electrocardiogram QT prolonged | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Glomerular filtration rate decreased | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Heart rate increased | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lipase increased | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Anemia | 1 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Protein total increased | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thrombocytopenia | 1 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Leukopenia | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphopenia | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Red blood cell count decreased | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | White blood cell count decreased | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | White blood cell count increased | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 1 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 2 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 2 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Weight increased | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hematuria | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 1 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Renal failure | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Electrocardiogram QT prolonged | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood lactate dehydrogenase increased | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lipase increased | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Protein total increased | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphopenia | 1 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Glomerular filtration rate decreased | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood bilirubin increased | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Red blood cell count decreased | 1 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Anemia | 2 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Heart rate increased | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood insulin increased | 1 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Weight increased | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Renal failure | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Breath sounds abnormal | 1 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatine increased | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thrombocytopenia | 2 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Cardiac enzymes increased | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 1 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood growth hormone increased | 1 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | White blood cell count increased | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Leukopenia | 2 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hematuria | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Weight decreased | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | White blood cell count decreased | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Glomerular filtration rate decreased | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Breath sounds abnormal | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Anemia | 2 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thrombocytopenia | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Leukopenia | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood lactate dehydrogenase increased | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 2 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphopenia | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Protein total increased | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Red blood cell count decreased | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood bilirubin increased | 1 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Weight decreased | 2 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | White blood cell count decreased | 1 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | White blood cell count increased | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood growth hormone increased | 1 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 3 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 2 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatine increased | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 2 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood insulin increased | 1 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Weight increased | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Electrocardiogram QT prolonged | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Renal failure | 1 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lipase increased | 1 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Heart rate increased | 1 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Cardiac enzymes increased | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hematuria | 1 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatine increased | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Cardiac enzymes increased | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | White blood cell count increased | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Glomerular filtration rate decreased | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood lactate dehydrogenase increased | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thrombocytopenia | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Breath sounds abnormal | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hematuria | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood insulin increased | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Anemia | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lipase increased | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Weight increased | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Renal failure | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Protein total increased | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood bilirubin increased | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Electrocardiogram QT prolonged | 1 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Red blood cell count decreased | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Heart rate increased | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphopenia | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Weight decreased | 1 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | White blood cell count decreased | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood growth hormone increased | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Leukopenia | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hematuria | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lipase increased | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Anemia | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | White blood cell count increased | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lymphopenia | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood lactate dehydrogenase increased | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Heart rate increased | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thrombocytopenia | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Glomerular filtration rate decreased | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Leukopenia | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 1 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatine increased | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Weight increased | 1 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Renal failure | 1 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Red blood cell count decreased | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Weight decreased | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | White blood cell count decreased | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Cardiac enzymes increased | 1 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood bilirubin increased | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Electrocardiogram QT prolonged | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Breath sounds abnormal | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood growth hormone increased | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood insulin increased | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Protein total increased | 0 Participants |
Primary
Number of Participants With Dose-Limiting Toxicities (DLTs)
A DLT was defined as any grade greater than or equal to (\>=) 3 treatment-related non-hematologic toxicity that occurred during the DLT assessment period with the following exceptions: Grade less than (\<) 4 serum-high glucose (fasting) with duration of \< 24 hours; Grade 3 fever (in the absence of neutropenia) defined as \> 40.0 degree centigrade (°C) \[greater than (\>) 104.0°F\] that resolved to normal or baseline within 24 hours of treatment and was not considered an SAE; or Grade 3 rigors/chills that responded to optimal therapy; any Grade \>= 3 treatment-related hematologic toxicity that occurred during the DLT assessment period.
Time frame: Cycle 1 Day 1 through Cycle 1 Day 21
Population: The Safety Population included all participants who had received any MEDI-573 treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
AEs were any unfavorable and unintended signs (including abnormal laboratory findings), symptoms, or diseases temporally associated with the use of MEDI-573, whether or not considered related to MEDI-573. A SAE was any AE that resulted in: death; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; was life-threatening; was a congenital anomaly/birth defect in the offspring of a study participant; or was an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes above. TEAEs were defined as AEs present at baseline that worsened in intensity after administration of MEDI-573, or events absent at baseline that emerged after administration of MEDI-573, up to 30 days after the last dose.
Time frame: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
Population: The Safety Population included all participants who had received any MEDI-573 treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | TEAEs | 4 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Treatment emergent SAEs | 2 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | TEAEs | 3 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Treatment emergent SAEs | 1 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | TEAEs | 13 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Treatment emergent SAEs | 4 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | TEAEs | 3 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Treatment emergent SAEs | 1 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | TEAEs | 13 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Treatment emergent SAEs | 6 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | TEAEs | 3 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Treatment emergent SAEs | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | TEAEs | 3 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Treatment emergent SAEs | 3 Participants |
Primary
Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs
Vital signs and physical findings included parameters such as heart rate, blood pressure, temperature, and respiratory rate. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-573 or events absent at baseline that emerged after administration of MEDI-573, for the period extending to 30 days after the last dose.
Time frame: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
Population: The Safety Population included all participants who had received any MEDI-573 treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Tachycardia | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Orthostatic hypotension | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Breath sounds abnormal | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Pyrexia | 1 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Heart rate increased | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Hypertension | 0 Participants |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Hypotension | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Hypertension | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Pyrexia | 1 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Tachycardia | 1 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Breath sounds abnormal | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Hypotension | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Heart rate increased | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Orthostatic hypotension | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Tachycardia | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Breath sounds abnormal | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Hypotension | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Heart rate increased | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Hypertension | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Pyrexia | 1 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Orthostatic hypotension | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Hypotension | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Orthostatic hypotension | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Breath sounds abnormal | 1 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Tachycardia | 1 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Heart rate increased | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Pyrexia | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Hypertension | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Hypertension | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Heart rate increased | 1 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Hypotension | 2 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Tachycardia | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Breath sounds abnormal | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Pyrexia | 1 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Orthostatic hypotension | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Hypotension | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Orthostatic hypotension | 1 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Tachycardia | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Heart rate increased | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Pyrexia | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Hypertension | 1 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Breath sounds abnormal | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Breath sounds abnormal | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Tachycardia | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Hypotension | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Heart rate increased | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Hypertension | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Orthostatic hypotension | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs | Pyrexia | 0 Participants |
Primary
Optimal Biologically Effective Dose (OBED) of MEDI-573
The OBED was defined as the dose at which all circulating insulin-like growth factor (IGF)-1 and IGF-2 ligand was sequestered by MEDI-573.
Time frame: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
Population: Safety population: Participants in the dose-escalation phase were analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Optimal Biologically Effective Dose (OBED) of MEDI-573 | 5 mg/kg |
Secondary
Area Under the Serum Concentration-time Curve Over the First Dosing Interval (AUCτ)
Area under the serum concentration-time curve over the first dosing interval.
Time frame: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
Population: The Safety Population included all participants who had received any MEDI-573 treatment. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Area Under the Serum Concentration-time Curve Over the First Dosing Interval (AUCτ) | 9.59 mcg*day/mL | Standard Deviation 5.12 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Area Under the Serum Concentration-time Curve Over the First Dosing Interval (AUCτ) | 90.8 mcg*day/mL | Standard Deviation 18.6 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Area Under the Serum Concentration-time Curve Over the First Dosing Interval (AUCτ) | 431 mcg*day/mL | Standard Deviation 135 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Area Under the Serum Concentration-time Curve Over the First Dosing Interval (AUCτ) | 631 mcg*day/mL | Standard Deviation 288 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Area Under the Serum Concentration-time Curve Over the First Dosing Interval (AUCτ) | 1950 mcg*day/mL | Standard Deviation 917 |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Area Under the Serum Concentration-time Curve Over the First Dosing Interval (AUCτ) | 3510 mcg*day/mL | Standard Deviation 1230 |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Area Under the Serum Concentration-time Curve Over the First Dosing Interval (AUCτ) | 5790 mcg*day/mL | Standard Deviation 3390 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Area Under the Serum Concentration-time Curve Over the First Dosing Interval (AUCτ) | 227 mcg*day/mL | Standard Deviation 99.8 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Area Under the Serum Concentration-time Curve Over the First Dosing Interval (AUCτ) | 1280 mcg*day/mL | Standard Deviation 392 |
Secondary
Dose-normalized Area Under the Serum Concentration Time Curve Over the First Dosing Interval (AUCτ/Dose)
The AUCtau/dose was a measure of dose-normalized area under the serum concentration-time curve over the first dosing interval.
Time frame: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
Population: The Safety Population included all participants who had received any MEDI-573 treatment. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Dose-normalized Area Under the Serum Concentration Time Curve Over the First Dosing Interval (AUCτ/Dose) | 0.245 mcg*day/mL/mg | Standard Deviation 0.145 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Dose-normalized Area Under the Serum Concentration Time Curve Over the First Dosing Interval (AUCτ/Dose) | 0.749 mcg*day/mL/mg | Standard Deviation 0.176 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Dose-normalized Area Under the Serum Concentration Time Curve Over the First Dosing Interval (AUCτ/Dose) | 0.962 mcg*day/mL/mg | Standard Deviation 0.041 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Dose-normalized Area Under the Serum Concentration Time Curve Over the First Dosing Interval (AUCτ/Dose) | 0.955 mcg*day/mL/mg | Standard Deviation 0.401 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Dose-normalized Area Under the Serum Concentration Time Curve Over the First Dosing Interval (AUCτ/Dose) | 1.47 mcg*day/mL/mg | Standard Deviation 0.624 |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Dose-normalized Area Under the Serum Concentration Time Curve Over the First Dosing Interval (AUCτ/Dose) | 1.46 mcg*day/mL/mg | Standard Deviation 0.526 |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Dose-normalized Area Under the Serum Concentration Time Curve Over the First Dosing Interval (AUCτ/Dose) | 1.70 mcg*day/mL/mg | Standard Deviation 0.976 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Dose-normalized Area Under the Serum Concentration Time Curve Over the First Dosing Interval (AUCτ/Dose) | 0.53 mcg*day/mL/mg | Standard Deviation 0.233 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Dose-normalized Area Under the Serum Concentration Time Curve Over the First Dosing Interval (AUCτ/Dose) | 0.981 mcg*day/mL/mg | Standard Deviation 0.275 |
Secondary
Dose Normalized Cmax (Cmax/Dose) After the First Dose
The Cmax/dose was the dose-normalized maximum serum concentration of MEDI-573.
Time frame: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
Population: The Safety Population included all participants who had received any MEDI-573 treatment. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Dose Normalized Cmax (Cmax/Dose) After the First Dose | 0.319 mcg/mL/mg | Standard Deviation 0.154 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Dose Normalized Cmax (Cmax/Dose) After the First Dose | 0.593 mcg/mL/mg | Standard Deviation 0.122 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Dose Normalized Cmax (Cmax/Dose) After the First Dose | 0.401 mcg/mL/mg | Standard Deviation 0.054 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Dose Normalized Cmax (Cmax/Dose) After the First Dose | 0.393 mcg/mL/mg | Standard Deviation 0.129 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Dose Normalized Cmax (Cmax/Dose) After the First Dose | 0.422 mcg/mL/mg | Standard Deviation 0.168 |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Dose Normalized Cmax (Cmax/Dose) After the First Dose | 0.240 mcg/mL/mg | Standard Deviation 0.072 |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Dose Normalized Cmax (Cmax/Dose) After the First Dose | 0.352 mcg/mL/mg | Standard Deviation 0.178 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Dose Normalized Cmax (Cmax/Dose) After the First Dose | 0.267 mcg/mL/mg | Standard Deviation 0.11 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Dose Normalized Cmax (Cmax/Dose) After the First Dose | 0.314 mcg/mL/mg | Standard Deviation 0.095 |
Secondary
Duration of Response
Duration of response was defined as the duration from the first documentation of objective response (confirmed CR or PR) to the first documented disease progression.
Time frame: From study entry through the end of the study, up to 3.5 years
Population: Participants in efficacy evaluable population and who achieved objective response were analyzed. As no participants achieved objective response in this study, number of participants analyzed for this outcome measure were zero.
Secondary
Maximum Observed Serum Concentration (Cmax) After the First Dose
The Cmax was the maximum observed serum concentration of MEDI-573.
Time frame: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
Population: The Safety Population included all participants who had received any MEDI-573 treatment. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Maximum Observed Serum Concentration (Cmax) After the First Dose | 11.6 microgram per milliliter (mcg/mL) | Standard Deviation 5.54 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Maximum Observed Serum Concentration (Cmax) After the First Dose | 71.8 microgram per milliliter (mcg/mL) | Standard Deviation 12.5 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Maximum Observed Serum Concentration (Cmax) After the First Dose | 166 microgram per milliliter (mcg/mL) | Standard Deviation 37.7 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Maximum Observed Serum Concentration (Cmax) After the First Dose | 264 microgram per milliliter (mcg/mL) | Standard Deviation 121 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Maximum Observed Serum Concentration (Cmax) After the First Dose | 560 microgram per milliliter (mcg/mL) | Standard Deviation 251 |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Maximum Observed Serum Concentration (Cmax) After the First Dose | 588 microgram per milliliter (mcg/mL) | Standard Deviation 213 |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Maximum Observed Serum Concentration (Cmax) After the First Dose | 1200 microgram per milliliter (mcg/mL) | Standard Deviation 621 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Maximum Observed Serum Concentration (Cmax) After the First Dose | 115 microgram per milliliter (mcg/mL) | Standard Deviation 42.6 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Maximum Observed Serum Concentration (Cmax) After the First Dose | 412 microgram per milliliter (mcg/mL) | Standard Deviation 141 |
Secondary
Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI-573
Two methods were used to assess the immunogenicity data: an ECL-based method and measurement of neutralizing ADA. The titer was calculated by multiplying the minimum assay dilution factor by the reciprocal of the highest dilution factor which yielded an ECL multiple equal to or greater than the screening assay cut-point factor.
Time frame: Pre-infusion on Day 1 of each cycle, end of treatment, and 90 days after last dose MEDI-573 (up to 3.5 years)
Population: The Safety Population included all participants who had received any MEDI-573 treatment. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI-573 | 0 Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI-573 | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI-573 | 0 Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI-573 | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI-573 | 0 Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI-573 | 0 Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI-573 | 0 Participants |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI-573 | 0 Participants |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI-573 | 0 Participants |
Secondary
Objective Response Rate (ORR)
The ORR was defined as the proportion of participants with confirmed complete response (CR) or partial response (PR) according to the RECIST criteria The CR was defined as disappearance of all target and nontarget lesions and no new lesions; and PR was definded as \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline \[screening\]) and no new lesions.
Time frame: From study entry through the end of the study, up to 3.5 years
Population: The Efficacy Evaluable Population included all participants who received MEDI-573 and had at least one tumor assessment after the initiation of treatment. Participants in the dose-expansion phase were to have at least 1 lesion that was measurable using RECIST criteria, and a histologically confirmed diagnosis of advanced urothelial carcinoma.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Objective Response Rate (ORR) | 0 Percentage of Participants |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Objective Response Rate (ORR) | 0 Percentage of Participants |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Objective Response Rate (ORR) | 0 Percentage of Participants |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Objective Response Rate (ORR) | 0 Percentage of Participants |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Objective Response Rate (ORR) | 0 Percentage of Participants |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Objective Response Rate (ORR) | 0 Percentage of Participants |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Objective Response Rate (ORR) | 0 Percentage of Participants |
Secondary
Overall Survival
Overall survival (OS) was defined as the time from the start of treatment with MEDI-573 until death.
Time frame: From study entry through the end of the study, up to 3.5 years
Population: Efficacy Evaluable Population included all participants who received MEDI-573 and had at least 1 tumor assessment after initiation of treatment. Participants in dose-expansion phase had at least 1 measurable lesion and histologically diagnosis of advanced urothelial carcinoma. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Overall Survival | 5.3 Months |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Overall Survival | 13.6 Months |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Overall Survival | 12.3 Months |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Overall Survival | 2.5 Months |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Overall Survival | 4.0 Months |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Overall Survival | 7.9 Months |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Overall Survival | 4.7 Months |
Secondary
Progression-free Survival (PFS)
Progression-free survival (PFS) was defined as the duration from the start of treatment with MEDI-573 until the documentation of disease progression or death due to any cause, whichever occurred first.
Time frame: From study entry through the end of the study, up to 3.5 years
Population: Efficacy Evaluable Population included all participants who received MEDI-573 and had at least 1 tumor assessment after initiation of treatment. Participants in dose-expansion phase had at least 1 measurable lesion and histologically diagnosis of advanced urothelial carcinoma. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Progression-free Survival (PFS) | 1.0 Months |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Progression-free Survival (PFS) | 2.6 Months |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Progression-free Survival (PFS) | 1.4 Months |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Progression-free Survival (PFS) | 1.5 Months |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Progression-free Survival (PFS) | 1.3 Months |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Progression-free Survival (PFS) | NA Months |
Secondary
Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573
The suppression profiles of both IGF-1 and IGF-2 post administration of MEDI-573 in relation to time course of antibody concentrations in serum were evaluated during treatment.
Time frame: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
Population: The Safety Population included all participants who had received any MEDI-573 treatment. Here, N and n represent number of participants analyzed for this outcome measure and at specific time points, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 14.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 1.000 | 2.088 nanogram per milliliter (ng/ml) | Standard Deviation 0.964 |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.292 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.000 | 4.014 nanogram per milliliter (ng/ml) | Standard Deviation 2.177 |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 1.000 | 1.060 nanogram per milliliter (ng/ml) | Standard Deviation 0.828 |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 14.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.292 | 0.345 nanogram per milliliter (ng/ml) | Standard Deviation 0.227 |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.125 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.125 | 0.252 nanogram per milliliter (ng/ml) | Standard Deviation 0.111 |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 7.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 7.042 | 0.201 nanogram per milliliter (ng/ml) | Standard Deviation 0.087 |
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.000 | 2.773 nanogram per milliliter (ng/ml) | Standard Deviation 0.32 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.125 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.125 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.000 | 2.984 nanogram per milliliter (ng/ml) | Standard Deviation 1.753 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.292 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 1.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.292 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 14.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 14.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 7.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.000 | 9.264 nanogram per milliliter (ng/ml) | Standard Deviation 7.401 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 1.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 7.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 14.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.125 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 1.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.292 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.125 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.292 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 1.000 | 0.215 nanogram per milliliter (ng/ml) | Standard Deviation 0.117 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 14.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.000 | 2.431 nanogram per milliliter (ng/ml) | Standard Deviation 0.139 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 7.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 7.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.000 | 4.655 nanogram per milliliter (ng/ml) | Standard Deviation 3.437 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 7.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.125 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 14.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 21.000 | NA nanogram per milliliter (ng/ml) | — |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.000 | 1.721 nanogram per milliliter (ng/ml) | Standard Deviation 2.71 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 14.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.125 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.292 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 1.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 1.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 7.000 | 0.223 nanogram per milliliter (ng/ml) | Standard Deviation 0.115 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 7.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 14.000 | 0.232 nanogram per milliliter (ng/ml) | Standard Deviation 0.13 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 14.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 7.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 21.000 | 0.334 nanogram per milliliter (ng/ml) | — |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.000 | 1.879 nanogram per milliliter (ng/ml) | Standard Deviation 1.02 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.292 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 1.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.000 | 1.872 nanogram per milliliter (ng/ml) | Standard Deviation 0.862 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 14.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.125 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 21.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 14.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 21.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 7.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 7.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.125 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 7.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 1.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 14.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 14.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.292 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.000 | 1.440 nanogram per milliliter (ng/ml) | Standard Deviation 0.812 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 7.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.292 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 21.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 7.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 7.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.063 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.000 | 2.693 nanogram per milliliter (ng/ml) | Standard Deviation 2.855 |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 1.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 1.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.000 | 2.780 nanogram per milliliter (ng/ml) | Standard Deviation 0.694 |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 21.000 | 0.265 nanogram per milliliter (ng/ml) | Standard Deviation 0.189 |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.063 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 21.000 | 0.241 nanogram per milliliter (ng/ml) | Standard Deviation 0.147 |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.000 | 4.093 nanogram per milliliter (ng/ml) | Standard Deviation 1.039 |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 21.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.000 | 1.925 nanogram per milliliter (ng/ml) | Standard Deviation 1.374 |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 7.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 7.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.063 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 1.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.063 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 1.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 7.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 14.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 14.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 21.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.000 | 1.749 nanogram per milliliter (ng/ml) | Standard Deviation 0.643 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.125 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.292 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 1.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 7.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 14.000 | 0.360 nanogram per milliliter (ng/ml) | Standard Deviation 0.166 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 14.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 21.000 | 0.336 nanogram per milliliter (ng/ml) | Standard Deviation 0.177 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.000 | 2.689 nanogram per milliliter (ng/ml) | Standard Deviation 0.882 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 7.000 | 0.641 nanogram per milliliter (ng/ml) | Standard Deviation 0.546 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.125 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.292 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 1.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 7.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 21.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 7.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.292 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 14.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 14.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 7.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 1.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.292 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.125 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 1.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 0.000 | 2.099 nanogram per milliliter (ng/ml) | Standard Deviation 1.128 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 21.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 14.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 14.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 7.000 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-I at 7.000 | 0.196 nanogram per milliliter (ng/ml) | Standard Deviation 0.078 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.125 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.042 | NA nanogram per milliliter (ng/ml) | Standard Deviation 0 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573 | IGF-II at 0.000 | 2.213 nanogram per milliliter (ng/ml) | Standard Deviation 0.752 |
Secondary
Time to Progression
Time to disease progression (TTP) was defined as the duration from the start of treatment with MEDI-573 until the documentation of disease progression.
Time frame: From study entry through the end of the study, up to 3.5 years
Population: Efficacy Evaluable Population included all participants who received MEDI-573 and had at least 1 tumor assessment after initiation of treatment. Participants in dose-expansion phase had at least 1 measurable lesion and histologically diagnosis of advanced urothelial carcinoma. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Time to Progression | 1.0 Months |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Time to Progression | 2.6 Months |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Time to Progression | 1.4 Months |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Time to Progression | 1.5 Months |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Time to Progression | 1.3 Months |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Time to Progression | NA Months |
Secondary
Time to Reach Maximum Observed Concentration (Tmax) After the First Dose
The tmax was defined as actual sampling time to reach the maximum observed serum concentration of MEDI-573.
Time frame: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
Population: The Safety Population included all participants who had received any MEDI-573 treatment. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Time to Reach Maximum Observed Concentration (Tmax) After the First Dose | 0.04 Day |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Time to Reach Maximum Observed Concentration (Tmax) After the First Dose | 0.04 Day |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Time to Reach Maximum Observed Concentration (Tmax) After the First Dose | 0.04 Day |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Time to Reach Maximum Observed Concentration (Tmax) After the First Dose | 0.04 Day |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Time to Reach Maximum Observed Concentration (Tmax) After the First Dose | 0.28 Day |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Time to Reach Maximum Observed Concentration (Tmax) After the First Dose | 0.06 Day |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Time to Reach Maximum Observed Concentration (Tmax) After the First Dose | 0.06 Day |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Time to Reach Maximum Observed Concentration (Tmax) After the First Dose | 0.04 Day |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Time to Reach Maximum Observed Concentration (Tmax) After the First Dose | 0.06 Day |
Secondary
Time to Response (TTR)
Time to response was defined as the duration from the start of treatment with MEDI-573 to the first documentation of objective response (confirmed CR or PR) and was only assessed in participants who had achieved objective response.
Time frame: From study entry through the end of the study, up to 3.5 years
Population: Participants in efficacy evaluable population and who achieved objective response were analyzed. As no participants achieved objective response in this study, number of participants analyzed for this outcome measure were zero.
Secondary
Trough Serum Concentration (Ctrough) After the First Dose
The Ctrough was the lowest serum concentration of MEDI-573 within a dosing interval.
Time frame: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
Population: The Safety Population included all participants who had received any MEDI-573 treatment. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | Trough Serum Concentration (Ctrough) After the First Dose | 1.04 mcg/mL | Standard Deviation 0.919 |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | Trough Serum Concentration (Ctrough) After the First Dose | 1.98 mcg/mL | Standard Deviation 0.377 |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | Trough Serum Concentration (Ctrough) After the First Dose | 17.3 mcg/mL | Standard Deviation 10.2 |
| MEDI-573 10 mg/Kg QWk Dose Escalation | Trough Serum Concentration (Ctrough) After the First Dose | 34.6 mcg/mL | Standard Deviation 26.8 |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | Trough Serum Concentration (Ctrough) After the First Dose | 138 mcg/mL | Standard Deviation 77.8 |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | Trough Serum Concentration (Ctrough) After the First Dose | 32.9 mcg/mL | Standard Deviation 28.2 |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | Trough Serum Concentration (Ctrough) After the First Dose | 63.5 mcg/mL | Standard Deviation 59.5 |
| MEDI-573 5 mg/Kg QWk Dose Expansion | Trough Serum Concentration (Ctrough) After the First Dose | 5.27 mcg/mL | Standard Deviation 4.8 |
| MEDI-573 15 mg/Kg QWk Dose Expansion | Trough Serum Concentration (Ctrough) After the First Dose | 77.8 mcg/mL | Standard Deviation 33.5 |