A Dose Escalation, Dose Expansion Study to Evaluate the S... | NCT00816400 | Trialant
NCT00816400
Sponsor
MedImmune LLC
Status
Completed
Last Update Posted
Jun 26, 2018Actual
Enrollment
49Actual
Phase
Phase 1
Conditions
Cancer
Interventions
MEDI-575
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT00816400
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
MI-CP187
Secondary IDs
Not provided
Brief Title
A Dose Escalation, Dose Expansion Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-575, in Subjects With Advanced Tumors.
Official Title
A Phase 1, Multicenter, Open-label, Single-arm, Dose-escalation Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-575, a Fully Human Monoclonal Antibody Directed Against Platelet-derived Growth Factor Receptor Alpha (PDGFRα), in Subjects With Advanced Solid Tumors Refractory to Standard Therapy or for Which No Standard Therapy Exists
Acronym
MEDI-575
Organization
MedImmune LLCINDUSTRY
Status Module
Record Verification Date
Apr 2018
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Mar 2, 2009Actual
Primary Completion Date
Jan 19, 2012Actual
Completion Date
Jan 19, 2012Actual
First Submitted Date
Dec 23, 2008
First Submission Date that Met QC Criteria
Dec 30, 2008
First Posted Date
Jan 1, 2009Estimated
Results Waived
Not provided
Results First Submitted Date
Dec 21, 2016
Results First Submitted that Met QC Criteria
Apr 10, 2017
Results First Posted Date
Apr 11, 2017Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Apr 3, 2018
Last Update Posted Date
Jun 26, 2018Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
MedImmune LLCINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
Evaluate the safety, tolerability and the tolerated maximum dose of MEDI-575 in adult subjects with advanced solid tumors refractory to standard therapy or for which no standard therapy exists.
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
An adverse event (AE) is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Treatment-emergent AEs (TEAEs) are events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug, for the period extending to 30 days after the last dose of study drug. Participants were counted only once for each event and by the highest event severity, regardless of how many events the participant experienced. The AEs were summarized using Medical Dictionary for Regulatory Activities (MedDRA) version 14.1.
From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Number of Participants With Serious Adverse Events
A serious AE (SAE) is any AE that results in death, is immediately life threatening, require (or prolong) inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, or is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above. Treatment-emergent SAEs that emerged after start of study drug were reported. Participants were counted only once for each event and by the highest event severity, regardless of how many events the participant experienced. The SAEs were summarized using MedDRA version 14.1.
From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Treatment-emergent Adverse Events Related to Laboratory Parameters
Laboratory evaluations of blood and urine samples were performed, including hematology (complete blood count, differential, and platelet count); serum chemistry (SrChem) aspartate transaminase (AST), alanine transaminase, total bilirubin, creatinine, alkaline phosphatase, sodium, potassium, chloride, phosphorus, calcium, glucose, magnesium, albumin, and lactate dehydrogenase); and routine urinalysis. Number of participants with TEAEs related to laboratory evaluations were reported.
Secondary Outcomes
Measure
Description
Time Frame
Pharmacokinetics (PK) of MEDI-575 After the First Dose: Observed Maximum Serum Concentration (Cmax)
The concentration of MEDI-575 quantitatively determined in serum samples using a validated electrochemiluminescence (ECL) PK assay. The Cmax after the first dose was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed advanced solid tumor for which no curative or standard therapies exist
Karnofsky performance status of ≥ 60
Life expectancy of >12 weeks
Adequate hematologic and organ function
Negative serum pregnancy test (women only)
Two methods of birth control for female participants of child-bearing potential or male participants with their female partners of child-bearing potential
Exclusion Criteria:
Prior chemotherapy or investigational treatment within 4 weeks of study drug administration
Prior biological or immunological treatment within 6 weeks of study drug administration
Concurrent therapy for of cancer
Major surgery within four weeks or minor surgery within two weeks of study drug administration
History of diabetes or current treatment for 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
History of other invasive malignancy within 5 years (exceptions are cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that are surgically cured)
Significant active infection
Known brain metastases
Pregnancy or lactation or plans to become pregnant while on study
Becerra CR, Conkling P, Vogelzang N, Wu H, Hong S, Narwal R, Liang M, Tavakkoli F, Pandya N. A phase I dose-escalation study of MEDI-575, a PDGFRalpha monoclonal antibody, in adults with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Nov;74(5):917-25. doi: 10.1007/s00280-014-2567-9. Epub 2014 Aug 23.
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Drug: MEDI-575
MEDI-575, 9.0 mg/kg QWk Expansion Phase
Experimental
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Drug: MEDI-575
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
Experimental
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations
All 12-lead electrocardiograms (ECGs) performed during the study were obtained in triplicate (ie, 3 ECGs were obtained within a 5-minute time interval) and analyzed. ECG parameters included heart rate (high and low), QT interval, QTcB (corrected QT interval per Bazett's formula), and QTcF (corrected QT interval per Fridericia's formula). Number of participants with TEAEs related to ECG after the start of study drug were reported.
From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Treatment-emergent Adverse Events Related to Vital Sign Parameters
Vital signs (temperature, blood pressure, pulse rate, and respiratory rate) were performed throughout the study. The TEAEs related to vital signs in participants were reported.
From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Maximum Tolerated Dose (MTD)
For the dose escalation phase, a minimum of 21 evaluable participants (3 participants each in Dose Cohorts 1 through 7) were required for this study if Dose Limiting Toxicities (DLTs) do not occur. If a DLT does occur among the first 3 participants in a cohort, 3 additional participants were to be added to the cohort; 3 more participants were to be added to a cohort to determine the MTD if only 3 participants have been previously treated at that dose. The MTD is the maximum dose at which no more than 1 out of 6 participants experienced a DLT. A DLT is defined as any grade 3 or higher hematologic toxicity or any grade 3 or higher non-hematologic toxicity except grade 3 fever (in the absence of neutropenia) or grade 3 rigors/chills.
From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Time to Maximum Concentration (Tmax)
The time to reach maximum serum concentration after the first dose of MEDI-575 was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Dose-normalized Maximum Serum Concentration (Cmax/Dose)
The Cmax/dose after the first dose of MEDI-575 was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Trough Serum Concentration (Ctrough)
The Ctrough ie, measured concentration at the end of a dosing interval (taken directly before next dose administration) of MEDI-575 was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCÏ„)
The AUCÏ„ was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Dose-normalized Area Under the Serum Concentration-time Curve (AUCÏ„/Dose)
The AUCÏ„/dose was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit
Blood samples for immunogenicity assessments were collected from participants prior to the initiation of infusion of each treatment cycle of MEDI-575. Anti-MEDI-575 antibodies were analyzed using the electro-chemiluminescence (ECL) based method. Only the number of participants positive for anti-MEDI-575 antibodies at any visit are presented.
Preinfusion on Cycle 1 Day 1 and 30 days after the last dose, up to 112 weeks
Percentage of Participants With Objective Response
Objective response rate is defined as the proportion of participants with confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after the initial documentation of response. The CR is defined as disappearance of all target and non-target lesions, and normalization of tumor marker level. The PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
From study entry through the end of the study, up to 34 months
Time to Response
Time to response was measured from the start of treatment with MEDI-575 to the first documentation of objective response (confirmed CR or PR). The time to response is assessed only for the participants who have achieved the objective response.
Duration of Response
Duration of response is defined as the duration from the first documentation of objective response to the first documented disease progression. Disease progression is defined according to RECIST guidelines (ie, at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions). The duration of response was censored on the date of last tumor assessment documenting absence of disease progression for participants who have no documented progression prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. Duration of response was calculated for the subgroup of participants with an objective response.
Time to Progression
Time to progression (TTP) is defined as time from the start of treatment with MEDI-575 until the documentation of disease progression. Disease progression is defined according to RECIST guidelines (ie, at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions). The TTP was censored on the date of last tumor assessment documenting absence of tumor progression for participants who have no documented progression prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. TTP was censored on the first date of treatment for the participants with no tumor assessments after the start of MEDI-575 treatment.
Start of treatment with MEDI-575 until the documentation of disease progression, up to 24 months
Progression-free Survival
Progression-free survival (PFS) is defined as time from the start of treatment with MEDI-575 until the documentation of disease progression or death due to any cause, whichever occurred first. Disease progression is defined according to RECIST guidelines (ie, at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions). PFS was censored on the date of last tumor assessment documenting absence of tumor progression for participants who have no documented progression and were still alive prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. PFS was censored on the first date of treatment for the participants with no tumor assessments after the start of MEDI-575 treatment.
Start of treatment with MEDI-575 until the documentation of disease progression or death due to any cause whichever occurs first, up to 24 months
Overall Survival
Overall survival (OS) is defined as the time from the start of treatment with MEDI-575 until death. For the participants who were alive at the end of study or lost to follow-up, OS was censored on the last date when participants were known to be alive.
From the start of treatment with MEDI-575 until death or end of study, up to 33 months
Indianapolis
Indiana
United States
Research Site
Las Vegas
Nevada
United States
Research Site
Dallas
Texas
United States
Research Site
Norfolk
Virginia
United States
PMCID: PMC3749129:
Circulating Tumor Cells: Application as a Biomarker for Molecular Characterization and Predictor of Survival in an All-Comer Solid Tumor Phase I Clinical Study
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
FG007
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
FG008
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
BG007
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
BG008
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
BG009
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0003
BG0013
BG0025
BG0033
BG0043
BG0053
BG0063
BG0076
BG0086
BG00935
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00058.0± 16.5
BG00165.0± 8.5
BG00260.2± 8.5
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0001
BG0013
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Number of Participants With Adverse Events
An adverse event (AE) is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Treatment-emergent AEs (TEAEs) are events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug, for the period extending to 30 days after the last dose of study drug. Participants were counted only once for each event and by the highest event severity, regardless of how many events the participant experienced. The AEs were summarized using Medical Dictionary for Regulatory Activities (MedDRA) version 14.1.
Safety population: All participants who have received any treatment of MEDI-575
Posted
Number
Participants
From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG007
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG008
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Units
Counts
Participants
OG0003
OG0013
OG0025
OG003
Title
Denominators
Categories
Title
Measurements
OG0003
OG0013
OG0025
OG003
Primary
Number of Participants With Serious Adverse Events
A serious AE (SAE) is any AE that results in death, is immediately life threatening, require (or prolong) inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, or is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above. Treatment-emergent SAEs that emerged after start of study drug were reported. Participants were counted only once for each event and by the highest event severity, regardless of how many events the participant experienced. The SAEs were summarized using MedDRA version 14.1.
Safety population
Posted
Number
Participants
From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Primary
Treatment-emergent Adverse Events Related to Laboratory Parameters
Laboratory evaluations of blood and urine samples were performed, including hematology (complete blood count, differential, and platelet count); serum chemistry (SrChem) aspartate transaminase (AST), alanine transaminase, total bilirubin, creatinine, alkaline phosphatase, sodium, potassium, chloride, phosphorus, calcium, glucose, magnesium, albumin, and lactate dehydrogenase); and routine urinalysis. Number of participants with TEAEs related to laboratory evaluations were reported.
Safety population
Posted
Number
Participants
From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Primary
Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations
All 12-lead electrocardiograms (ECGs) performed during the study were obtained in triplicate (ie, 3 ECGs were obtained within a 5-minute time interval) and analyzed. ECG parameters included heart rate (high and low), QT interval, QTcB (corrected QT interval per Bazett's formula), and QTcF (corrected QT interval per Fridericia's formula). Number of participants with TEAEs related to ECG after the start of study drug were reported.
Safety population
Posted
Number
Participants
From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Primary
Treatment-emergent Adverse Events Related to Vital Sign Parameters
Vital signs (temperature, blood pressure, pulse rate, and respiratory rate) were performed throughout the study. The TEAEs related to vital signs in participants were reported.
Safety population
Posted
Number
Participants
From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
For the dose escalation phase, a minimum of 21 evaluable participants (3 participants each in Dose Cohorts 1 through 7) were required for this study if Dose Limiting Toxicities (DLTs) do not occur. If a DLT does occur among the first 3 participants in a cohort, 3 additional participants were to be added to the cohort; 3 more participants were to be added to a cohort to determine the MTD if only 3 participants have been previously treated at that dose. The MTD is the maximum dose at which no more than 1 out of 6 participants experienced a DLT. A DLT is defined as any grade 3 or higher hematologic toxicity or any grade 3 or higher non-hematologic toxicity except grade 3 fever (in the absence of neutropenia) or grade 3 rigors/chills.
MTD evaluable population includes all participants in the dose escalation phase who have received at least 1 full cycle of MEDI-575 and have completed the safety follow-up through the DLT-evaluation period, or who experienced a DLT. The MTD dose was not evaluated as there were no DLTs reported in this study.
Posted
Number
Milligrams per kilogram (mg/kg)
From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Secondary
Pharmacokinetics (PK) of MEDI-575 After the First Dose: Observed Maximum Serum Concentration (Cmax)
The concentration of MEDI-575 quantitatively determined in serum samples using a validated electrochemiluminescence (ECL) PK assay. The Cmax after the first dose was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
All the participants who received first dose of MEDI-575 and for whom PK blood samples were collected and evaluated.
Posted
Mean
Standard Deviation
Micrograms per milliliter (μg/mL)
For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Secondary
PK of MEDI-575 After the First Dose: Time to Maximum Concentration (Tmax)
The time to reach maximum serum concentration after the first dose of MEDI-575 was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
All the participants who received first dose of MEDI-575 and for whom PK blood samples were collected and evaluated.
Posted
Mean
Standard Deviation
Day
For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Secondary
PK of MEDI-575 After the First Dose: Dose-normalized Maximum Serum Concentration (Cmax/Dose)
The Cmax/dose after the first dose of MEDI-575 was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
All the participants who received first dose of MEDI-575 and for whom PK blood samples were collected and evaluated.
Posted
Mean
Standard Deviation
μg/mL/mg
For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Secondary
PK of MEDI-575 After the First Dose: Trough Serum Concentration (Ctrough)
The Ctrough ie, measured concentration at the end of a dosing interval (taken directly before next dose administration) of MEDI-575 was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
All the participants who received first dose of MEDI-575 and from whom PK blood samples were collected and evaluated. Excluded participants were for whom it cannot be calculated (either number of doses received was less than 2 or standard deviation equals 0.000) or where dosing interval is more than 7 days or samples only collected up to 14 days.
Posted
Mean
Standard Deviation
μg/mL
For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
PK of MEDI-575 After the First Dose: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCÏ„)
The AUCÏ„ was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
All the participants who received first dose of MEDI-575 and from whom PK blood samples were collected and evaluated. Excluded participants were for whom it cannot be calculated (either number of doses received was less than 2 or standard deviation equals 0.000) or where dosing interval is more than 7 days or samples only collected up to 14 days.
Posted
Mean
Standard Deviation
μg·day/mL
For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
PK of MEDI-575 After the First Dose: Dose-normalized Area Under the Serum Concentration-time Curve (AUCÏ„/Dose)
The AUCÏ„/dose was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
All the participants who received first dose of MEDI-575 and from whom PK blood samples were collected and evaluated. Excluded participants were for whom it cannot be calculated (either number of doses received was less than 2 or standard deviation equals 0.000) or where dosing interval is more than 7 days or samples only collected up to 14 days.
Posted
Mean
Standard Deviation
μg·day/mL/mg
For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit
Blood samples for immunogenicity assessments were collected from participants prior to the initiation of infusion of each treatment cycle of MEDI-575. Anti-MEDI-575 antibodies were analyzed using the electro-chemiluminescence (ECL) based method. Only the number of participants positive for anti-MEDI-575 antibodies at any visit are presented.
Safety population
Posted
Number
Participants
Preinfusion on Cycle 1 Day 1 and 30 days after the last dose, up to 112 weeks
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Secondary
Percentage of Participants With Objective Response
Objective response rate is defined as the proportion of participants with confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after the initial documentation of response. The CR is defined as disappearance of all target and non-target lesions, and normalization of tumor marker level. The PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Efficacy evaluable population: All participants who have received any treatment of MEDI-575 and at least one tumor assessment after the initiation of MEDI-575.
Posted
Number
95% Confidence Interval
Percentage of participants
From study entry through the end of the study, up to 34 months
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Time to response was measured from the start of treatment with MEDI-575 to the first documentation of objective response (confirmed CR or PR). The time to response is assessed only for the participants who have achieved the objective response.
Efficacy evaluable population with an objective response. Time to response was not estimable as there were no participants with an objective response.
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Duration of response is defined as the duration from the first documentation of objective response to the first documented disease progression. Disease progression is defined according to RECIST guidelines (ie, at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions). The duration of response was censored on the date of last tumor assessment documenting absence of disease progression for participants who have no documented progression prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. Duration of response was calculated for the subgroup of participants with an objective response.
Efficacy evaluable population with an objective response. Duration of response was not estimable as there were no participants with an objective response.
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Time to progression (TTP) is defined as time from the start of treatment with MEDI-575 until the documentation of disease progression. Disease progression is defined according to RECIST guidelines (ie, at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions). The TTP was censored on the date of last tumor assessment documenting absence of tumor progression for participants who have no documented progression prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. TTP was censored on the first date of treatment for the participants with no tumor assessments after the start of MEDI-575 treatment.
Efficacy evaluable population. N= number of participants analyzed for this outcome measure
Posted
Median
95% Confidence Interval
Months
Start of treatment with MEDI-575 until the documentation of disease progression, up to 24 months
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Progression-free survival (PFS) is defined as time from the start of treatment with MEDI-575 until the documentation of disease progression or death due to any cause, whichever occurred first. Disease progression is defined according to RECIST guidelines (ie, at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions). PFS was censored on the date of last tumor assessment documenting absence of tumor progression for participants who have no documented progression and were still alive prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. PFS was censored on the first date of treatment for the participants with no tumor assessments after the start of MEDI-575 treatment.
Efficacy evaluable population. N= number of participants analyzed for this outcome measure
Posted
Median
95% Confidence Interval
Months
Start of treatment with MEDI-575 until the documentation of disease progression or death due to any cause whichever occurs first, up to 24 months
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Secondary
Overall Survival
Overall survival (OS) is defined as the time from the start of treatment with MEDI-575 until death. For the participants who were alive at the end of study or lost to follow-up, OS was censored on the last date when participants were known to be alive.
Efficacy evaluable population. N= number of participants analyzed for this outcome measure
Posted
Median
95% Confidence Interval
Months
From the start of treatment with MEDI-575 until death or end of study, up to 33 months
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Description
For treatment arms 9 mg/kg QWk and 25 mg/kg Q3Wk, both Escalation and Expansion Phase data are presented together for the Serious Adverse Events and Other Adverse Events.
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21 day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
2
3
3
3
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Pericardial effusion
Cardiac disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG0030 events0 affected3 at risk
EG0040 events0 affected3 at risk
EG0050 events0 affected9 at risk
EG0060 events0 affected3 at risk
Abdominal pain
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Multi-organ failure
General disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Femoral neck fracture
Injury, poisoning and procedural complications
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Fistula
Musculoskeletal and connective tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Metastases to central nervous system
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Non-small cell lung cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0023 events3 affected11 at risk
EG003
Cerebrovascular accident
Nervous system disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Convulsion
Nervous system disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Pneumothorax
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0022 events2 affected11 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG0031 events1 affected3 at risk
EG0040 events0 affected3 at risk
EG0053 events3 affected9 at risk
EG0060 events0 affected3 at risk
Leukocytosis
Blood and lymphatic system disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0022 events2 affected11 at risk
EG003
Ear discomfort
Ear and labyrinth disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0002 events1 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0002 events2 affected3 at risk
EG0012 events2 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0013 events1 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0004 events2 affected3 at risk
EG0014 events1 affected3 at risk
EG0022 events2 affected11 at risk
EG003
Oral pain
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0001 events1 affected3 at risk
EG0013 events1 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Asthenia
General disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Chills
General disorders
MedDRA 14.1
Systematic Assessment
EG0001 events1 affected3 at risk
EG0010 events0 affected3 at risk
EG0022 events2 affected11 at risk
EG003
Early satiety
General disorders
MedDRA 14.1
Systematic Assessment
EG0001 events1 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Fatigue
General disorders
MedDRA 14.1
Systematic Assessment
EG0002 events2 affected3 at risk
EG0014 events2 affected3 at risk
EG0026 events5 affected11 at risk
EG003
Oedema peripheral
General disorders
MedDRA 14.1
Systematic Assessment
EG0001 events1 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Weight decreased
Investigations
MedDRA 14.1
Systematic Assessment
EG0001 events1 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 14.1
Systematic Assessment
EG0002 events2 affected3 at risk
EG0014 events1 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0012 events2 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0025 events4 affected11 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Hypophosphataemia
Metabolism and nutrition disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0022 events2 affected11 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 14.1
Systematic Assessment
EG0001 events1 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 14.1
Systematic Assessment
EG0003 events1 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 14.1
Systematic Assessment
EG0001 events1 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 14.1
Systematic Assessment
EG0001 events1 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 14.1
Systematic Assessment
EG0001 events1 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 14.1
Systematic Assessment
EG0001 events1 affected3 at risk
EG0010 events0 affected3 at risk
EG0022 events2 affected11 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0012 events2 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0001 events1 affected3 at risk
EG0010 events0 affected3 at risk
EG0023 events3 affected11 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0012 events2 affected3 at risk
EG0025 events4 affected11 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0022 events2 affected11 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected11 at risk
EG003
Hypertension
Vascular disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Hypotension
Vascular disorders
MedDRA 14.1
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected11 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
Point of Contact
Title
Organization
Phone
Extension
Email
A Dose-escalation Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-575
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG007
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG008
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG007
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG008
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG007
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG008
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Units
Counts
Participants
OG0003
OG0013
OG0025
OG0033
OG0043
OG0053
OG0063
OG0076
OG0086
Title
Denominators
Categories
Supraventricular tachycardia
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG0060
OG0071
OG0080
Tachycardia
Title
Measurements
OG0000
OG0010
OG0021
OG003
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG007
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG008
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg
OG008
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG009
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg
OG008
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG009
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg
OG008
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG009
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Units
Counts
Participants
OG0003
OG0013
OG0025
OG0033
OG0043
OG0053
OG0063
OG0073
OG0086
OG0096
Title
Denominators
Categories
Title
Measurements
OG0000.292± 0.0404
OG0010.402± 0.125
OG0020.335± 0.107
OG0030.638± 0.171
OG0040.655± 0.191
OG0050.360± 0.0908
OG0060.259± 0.0614
OG0070.262± 0.0294
OG0080.372± 0.103
OG0090.357± 0.112
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg
OG008
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG009
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Units
Counts
Participants
OG0003
OG0013
OG0024
OG0033
OG0043
OG0053
OG0063
OG0073
OG0084
OG0094
Title
Denominators
Categories
Title
Measurements
OG0008.97± 2.85
OG00141.5± 13.8
OG00272.6± 35.3
OG003144± 18.0
OG004199± 55.3
OG00585.4± 40.8
OG006223± 25.2
OG007NA± NAThe mean was below limit of quantification and standard deviation cannot be calculated.
OG00859.0± 4.14
OG00974.9± 22.6
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg
OG008
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG009
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Units
Counts
Participants
OG0003
OG0013
OG0024
OG0033
OG0043
OG0053
OG0063
OG0073
OG0084
OG0094
Title
Denominators
Categories
Title
Measurements
OG000201± 12.5
OG001524± 166
OG002835± 339
OG0031870± 277
OG0042080± 205
OG0055100± 275
OG0068340± 372
OG00725.3± 7.69
OG008763± 144
OG0093760± 625
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg
OG008
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG009
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG007
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG008
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Units
Counts
Participants
OG0003
OG0013
OG0025
OG0033
OG0043
OG0053
OG0063
OG0076
OG0086
Title
Denominators
Categories
CYCLE 1 DAY 1
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0051
OG0060
OG0070
OG0081
30 DAY POST
Title
Measurements
OG0001
OG0010
OG0020
OG003
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG007
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG008
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Units
Counts
Participants
OG0003
OG0013
OG0024
OG0033
OG0043
OG0053
OG0063
OG0073
OG0084
Title
Denominators
Categories
Title
Measurements
OG0000(0.0 to 70.8)
OG0010(0.0 to 70.8)
OG0020(0.0 to 60.2)
OG0030(0.0 to 70.8)
OG0040(0.0 to 70.8)
OG0050(0.0 to 70.8)
OG0060(0.0 to 70.8)
OG0070(0.0 to 70.8)
OG0080(0.0 to 60.2)
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG007
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG008
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG0060
OG0070
OG0080
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG007
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG008
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG0060
OG0070
OG0080
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG007
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG008
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Units
Counts
Participants
OG0003
OG0012
OG0023
OG0033
OG0042
OG0053
OG0063
OG0073
OG0084
Title
Denominators
Categories
Title
Measurements
OG0001.8(1.5 to 24.8)
OG0011.4(1.2 to NA)The upper limit was not estimable
OG0021.2(0.5 to NA)The upper limit was not estimable
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG007
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG008
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Units
Counts
Participants
OG0003
OG0012
OG0023
OG0033
OG0042
OG0053
OG0063
OG0073
OG0084
Title
Denominators
Categories
Title
Measurements
OG0001.8(1.5 to 24.8)
OG0011.4(1.2 to NA)The upper limit was not estimable
OG0021.2(0.5 to NA)The upper limit was not estimable
OG0031.4(1.4 to 1.4)
OG0045.0(1.2 to 8.8)
OG0052.9(1.4 to 2.9)
OG0061.2(1.0 to 1.4)
OG0071.4(1.3 to 2.9)
OG0081.3(1.2 to 5.7)
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG007
MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
OG008
MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Units
Counts
Participants
OG0002
OG0013
OG0022
OG0033
OG0042
OG0053
OG0062
OG0072
OG0084
Title
Denominators
Categories
Title
Measurements
OG0009.0(3.5 to NA)The upper limit was not estimable
OG0013.7(3.6 to 9.0)
OG00217.2(7.4 to 27.0)
OG0035.5(3.5 to 14.1)
OG00419.4(3.4 to NA)The upper limit was not estimable
OG0058.7(1.8 to 10.5)
OG00610.3(1.8 to NA)The upper limit was not estimable
OG0075.4(2.6 to NA)The upper limit was not estimable