Cancer
Conditions
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.
Interventions
DRUGMEDI-575
MEDI-575 as an IV infusion
Sponsors
MedImmune LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * Clinically significant abnormality on ECG
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks | 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. |
| Number of Participants With Serious Adverse Events | From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks | 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. |
| Treatment-emergent Adverse Events Related to Laboratory Parameters | From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks | 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. |
| Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks | 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. |
| Treatment-emergent Adverse Events Related to Vital Sign Parameters | From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks | 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. |
| Maximum Tolerated Dose (MTD) | From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit | Preinfusion on Cycle 1 Day 1 and 30 days after the last dose, up to 112 weeks | 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. |
| Percentage of Participants With Objective Response | From study entry through the end of the study, up to 34 months | 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. |
| 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. |
| Pharmacokinetics (PK) of MEDI-575 After the First Dose: Observed Maximum Serum Concentration (Cmax) | 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. | 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. |
| Time to Progression | Start of treatment with MEDI-575 until the documentation of disease progression, up to 24 months | 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. |
| Progression-free Survival | 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 | 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. |
| Overall Survival | From the start of treatment with MEDI-575 until death or end of study, up to 33 months | 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. |
| 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. |
| PK of MEDI-575 After the First Dose: Time to Maximum Concentration (Tmax) | 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. | 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. |
| PK of MEDI-575 After the First Dose: Dose-normalized Maximum Serum Concentration (Cmax/Dose) | 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. | 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. |
| PK of MEDI-575 After the First Dose: Trough Serum Concentration (Ctrough) | 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. | 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. |
| PK of MEDI-575 After the First Dose: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCτ) | 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. | The AUCτ 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. |
| PK of MEDI-575 After the First Dose: Dose-normalized Area Under the Serum Concentration-time Curve (AUCτ/Dose) | 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. | The AUCτ/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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at 5 centers in the United States between March 2009 and January 2012.
Pre-assignment details
A total of 49 participants were screened, out of these, 35 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) 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. | 3 |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) 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. | 3 |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) 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. | 5 |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) 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. | 3 |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) 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. | 3 |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) 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. | 3 |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) 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. | 3 |
| 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. | 6 |
| 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. | 6 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 2 | 3 | 3 | 3 | 2 | 3 | 2 | 5 | 6 |
| Overall Study | In hospice care at the end of the study | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | MEDI-575, 9.0 mg/kg QWk Expansion Phase | MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 58.0 Years STANDARD_DEVIATION 16.5 | 65.0 Years STANDARD_DEVIATION 8.5 | 60.2 Years STANDARD_DEVIATION 8.5 | 66.3 Years STANDARD_DEVIATION 9.1 | 67.0 Years STANDARD_DEVIATION 10.5 | 58.0 Years STANDARD_DEVIATION 8.5 | 68.3 Years STANDARD_DEVIATION 8.4 | 68.2 Years STANDARD_DEVIATION 15.1 | 59.3 Years STANDARD_DEVIATION 6.6 | 63.3 Years STANDARD_DEVIATION 10.3 |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants | 3 Participants | 16 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 4 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 10 / 11 | 3 / 3 | 3 / 3 | 9 / 9 | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 | 1 / 3 | 8 / 11 | 0 / 3 | 0 / 3 | 2 / 9 | 2 / 3 |
Outcome results
Primary
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.
Time frame: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Maximum Tolerated Dose (MTD) | NA Milligrams per kilogram (mg/kg) |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Maximum Tolerated Dose (MTD) | NA Milligrams per kilogram (mg/kg) |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Maximum Tolerated Dose (MTD) | NA Milligrams per kilogram (mg/kg) |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Maximum Tolerated Dose (MTD) | NA Milligrams per kilogram (mg/kg) |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Maximum Tolerated Dose (MTD) | NA Milligrams per kilogram (mg/kg) |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Maximum Tolerated Dose (MTD) | NA Milligrams per kilogram (mg/kg) |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Maximum Tolerated Dose (MTD) | NA Milligrams per kilogram (mg/kg) |
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.
Time frame: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Population: Safety population: All participants who have received any treatment of MEDI-575
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Number of Participants With Adverse Events | 3 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Number of Participants With Adverse Events | 3 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Number of Participants With Adverse Events | 5 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Number of Participants With Adverse Events | 3 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Number of Participants With Adverse Events | 3 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Number of Participants With Adverse Events | 3 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Number of Participants With Adverse Events | 3 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Number of Participants With Adverse Events | 6 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Number of Participants With Adverse Events | 6 Participants |
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.
Time frame: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Number of Participants With Serious Adverse Events | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Number of Participants With Serious Adverse Events | 1 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Number of Participants With Serious Adverse Events | 3 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Number of Participants With Serious Adverse Events | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Number of Participants With Serious Adverse Events | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Number of Participants With Serious Adverse Events | 1 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Number of Participants With Serious Adverse Events | 2 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Number of Participants With Serious Adverse Events | 5 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Number of Participants With Serious Adverse Events | 1 Participants |
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.
Time frame: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Supraventricular tachycardia | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Tachycardia | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Tachycardia | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Supraventricular tachycardia | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Supraventricular tachycardia | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Tachycardia | 1 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Supraventricular tachycardia | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Tachycardia | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Tachycardia | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Supraventricular tachycardia | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Supraventricular tachycardia | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Tachycardia | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Tachycardia | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Supraventricular tachycardia | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Supraventricular tachycardia | 1 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Tachycardia | 1 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Supraventricular tachycardia | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | Tachycardia | 0 Participants |
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.
Time frame: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypokalaemia | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Proteinuria | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Thrombocytopenia | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Blood creatinine increased | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Haematuria | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Blood Alkaline phosphatase increased | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyponatraemia | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypomagnesaemia | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis: Urine colour abnormal | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyperkalaemia | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Leukocytosis | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Anaemia | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypophosphataemia | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: AST increased | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Urobilinogen urine increased | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyperglycaemia | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypercalcaemia | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Anaemia | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyponatraemia | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: AST increased | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Thrombocytopenia | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Proteinuria | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypokalaemia | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Haematuria | 2 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Blood Alkaline phosphatase increased | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Blood creatinine increased | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypercalcaemia | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Leukocytosis | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Urobilinogen urine increased | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyperglycaemia | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis: Urine colour abnormal | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyperkalaemia | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypomagnesaemia | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypophosphataemia | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypokalaemia | 3 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyponatraemia | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypophosphataemia | 1 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyperkalaemia | 1 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Proteinuria | 1 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypercalcaemia | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Haematuria | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyperglycaemia | 1 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis: Urine colour abnormal | 1 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Anaemia | 1 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Blood Alkaline phosphatase increased | 1 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Thrombocytopenia | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Leukocytosis | 1 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: AST increased | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypomagnesaemia | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Blood creatinine increased | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Urobilinogen urine increased | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Blood creatinine increased | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyperkalaemia | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Urobilinogen urine increased | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypokalaemia | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyponatraemia | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyperglycaemia | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypercalcaemia | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis: Urine colour abnormal | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Blood Alkaline phosphatase increased | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: AST increased | 1 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Thrombocytopenia | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Proteinuria | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Anaemia | 1 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypophosphataemia | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Leukocytosis | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Haematuria | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypomagnesaemia | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Anaemia | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Blood Alkaline phosphatase increased | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyperglycaemia | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Blood creatinine increased | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypercalcaemia | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyperkalaemia | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypokalaemia | 2 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypomagnesaemia | 1 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyponatraemia | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypophosphataemia | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis: Urine colour abnormal | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Urobilinogen urine increased | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Leukocytosis | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Haematuria | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Thrombocytopenia | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: AST increased | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Proteinuria | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Urobilinogen urine increased | 1 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Thrombocytopenia | 1 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Anaemia | 1 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypomagnesaemia | 1 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Proteinuria | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Haematuria | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyperkalaemia | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypokalaemia | 1 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyponatraemia | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypophosphataemia | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: AST increased | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Leukocytosis | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis: Urine colour abnormal | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Blood Alkaline phosphatase increased | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyperglycaemia | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypercalcaemia | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Blood creatinine increased | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Anaemia | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Urobilinogen urine increased | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Proteinuria | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyperglycaemia | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis: Urine colour abnormal | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Leukocytosis | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyponatraemia | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypokalaemia | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypomagnesaemia | 1 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Haematuria | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyperkalaemia | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Blood creatinine increased | 1 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Blood Alkaline phosphatase increased | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypophosphataemia | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: AST increased | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypercalcaemia | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Thrombocytopenia | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypokalaemia | 1 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyperkalaemia | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypophosphataemia | 1 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Anaemia | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyperglycaemia | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis: Urine colour abnormal | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypercalcaemia | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Urobilinogen urine increased | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Blood creatinine increased | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Blood Alkaline phosphatase increased | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: AST increased | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Leukocytosis | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Haematuria | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Thrombocytopenia | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Proteinuria | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypomagnesaemia | 1 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyponatraemia | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Proteinuria | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Urobilinogen urine increased | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypokalaemia | 1 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Thrombocytopenia | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Blood Alkaline phosphatase increased | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypercalcaemia | 1 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis: Urine colour abnormal | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyponatraemia | 1 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypomagnesaemia | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyperkalaemia | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Anaemia | 2 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hyperglycaemia | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Hypophosphataemia | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | Hematology: Leukocytosis | 1 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: Blood creatinine increased | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | Urinalysis:Haematuria | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Laboratory Parameters | SrChem: AST increased | 0 Participants |
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.
Time frame: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Hypertension | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Hypotension | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Pyrexia | 1 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Hypertension | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Pyrexia | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Hypotension | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Hypertension | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Pyrexia | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Hypotension | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Hypotension | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Pyrexia | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Hypertension | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Hypertension | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Hypotension | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Pyrexia | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Pyrexia | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Hypertension | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Hypotension | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Pyrexia | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Hypotension | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Hypertension | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Hypertension | 1 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Pyrexia | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Hypotension | 1 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Hypotension | 1 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Hypertension | 1 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Treatment-emergent Adverse Events Related to Vital Sign Parameters | Pyrexia | 0 Participants |
Secondary
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.
Population: Efficacy evaluable population with an objective response. Duration of response was not estimable as there were no participants with an objective response.
Secondary
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.
Time frame: Preinfusion on Cycle 1 Day 1 and 30 days after the last dose, up to 112 weeks
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit | CYCLE 1 DAY 1 | 0 Participants |
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit | 30 DAY POST | 1 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit | CYCLE 1 DAY 1 | 0 Participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit | 30 DAY POST | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit | CYCLE 1 DAY 1 | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit | 30 DAY POST | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit | CYCLE 1 DAY 1 | 0 Participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit | 30 DAY POST | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit | CYCLE 1 DAY 1 | 0 Participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit | 30 DAY POST | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit | 30 DAY POST | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit | CYCLE 1 DAY 1 | 1 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit | 30 DAY POST | 0 Participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit | CYCLE 1 DAY 1 | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit | CYCLE 1 DAY 1 | 0 Participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit | 30 DAY POST | 0 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit | CYCLE 1 DAY 1 | 1 Participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit | 30 DAY POST | 0 Participants |
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.
Time frame: From the start of treatment with MEDI-575 until death or end of study, up to 33 months
Population: Efficacy evaluable population. N= number of participants analyzed for this outcome measure
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Overall Survival | 9.0 Months |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Overall Survival | 3.7 Months |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Overall Survival | 17.2 Months |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Overall Survival | 5.5 Months |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Overall Survival | 19.4 Months |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Overall Survival | 8.7 Months |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Overall Survival | 10.3 Months |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Overall Survival | 5.4 Months |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Overall Survival | 5.9 Months |
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.
Time frame: From study entry through the end of the study, up to 34 months
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Percentage of Participants With Objective Response | 0 Percentage of participants |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Percentage of Participants With Objective Response | 0 Percentage of participants |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Percentage of Participants With Objective Response | 0 Percentage of participants |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Percentage of Participants With Objective Response | 0 Percentage of participants |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Percentage of Participants With Objective Response | 0 Percentage of participants |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Percentage of Participants With Objective Response | 0 Percentage of participants |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Percentage of Participants With Objective Response | 0 Percentage of participants |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Percentage of Participants With Objective Response | 0 Percentage of participants |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Percentage of Participants With Objective Response | 0 Percentage of participants |
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.
Time frame: 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.
Population: All the participants who received first dose of MEDI-575 and for whom PK blood samples were collected and evaluated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Pharmacokinetics (PK) of MEDI-575 After the First Dose: Observed Maximum Serum Concentration (Cmax) | 72.6 Micrograms per milliliter (μg/mL) | Standard Deviation 7 |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Pharmacokinetics (PK) of MEDI-575 After the First Dose: Observed Maximum Serum Concentration (Cmax) | 154 Micrograms per milliliter (μg/mL) | Standard Deviation 44.9 |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Pharmacokinetics (PK) of MEDI-575 After the First Dose: Observed Maximum Serum Concentration (Cmax) | 239 Micrograms per milliliter (μg/mL) | Standard Deviation 98.1 |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Pharmacokinetics (PK) of MEDI-575 After the First Dose: Observed Maximum Serum Concentration (Cmax) | 590 Micrograms per milliliter (μg/mL) | Standard Deviation 124 |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Pharmacokinetics (PK) of MEDI-575 After the First Dose: Observed Maximum Serum Concentration (Cmax) | 632 Micrograms per milliliter (μg/mL) | Standard Deviation 20 |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Pharmacokinetics (PK) of MEDI-575 After the First Dose: Observed Maximum Serum Concentration (Cmax) | 670 Micrograms per milliliter (μg/mL) | Standard Deviation 131 |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Pharmacokinetics (PK) of MEDI-575 After the First Dose: Observed Maximum Serum Concentration (Cmax) | 918 Micrograms per milliliter (μg/mL) | Standard Deviation 111 |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Pharmacokinetics (PK) of MEDI-575 After the First Dose: Observed Maximum Serum Concentration (Cmax) | 10.9 Micrograms per milliliter (μg/mL) | Standard Deviation 0.512 |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Pharmacokinetics (PK) of MEDI-575 After the First Dose: Observed Maximum Serum Concentration (Cmax) | 240 Micrograms per milliliter (μg/mL) | Standard Deviation 44.1 |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Pharmacokinetics (PK) of MEDI-575 After the First Dose: Observed Maximum Serum Concentration (Cmax) | 549 Micrograms per milliliter (μg/mL) | Standard Deviation 143 |
Secondary
PK of MEDI-575 After the First Dose: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCτ)
The AUCτ 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.
Time frame: 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.
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | PK of MEDI-575 After the First Dose: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCτ) | 201 μg·day/mL | Standard Deviation 12.5 |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | PK of MEDI-575 After the First Dose: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCτ) | 524 μg·day/mL | Standard Deviation 166 |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | PK of MEDI-575 After the First Dose: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCτ) | 835 μg·day/mL | Standard Deviation 339 |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | PK of MEDI-575 After the First Dose: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCτ) | 1870 μg·day/mL | Standard Deviation 277 |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | PK of MEDI-575 After the First Dose: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCτ) | 2080 μg·day/mL | Standard Deviation 205 |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | PK of MEDI-575 After the First Dose: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCτ) | 5100 μg·day/mL | Standard Deviation 275 |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | PK of MEDI-575 After the First Dose: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCτ) | 8340 μg·day/mL | Standard Deviation 372 |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | PK of MEDI-575 After the First Dose: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCτ) | 25.3 μg·day/mL | Standard Deviation 7.69 |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | PK of MEDI-575 After the First Dose: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCτ) | 763 μg·day/mL | Standard Deviation 144 |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | PK of MEDI-575 After the First Dose: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCτ) | 3760 μg·day/mL | Standard Deviation 625 |
Secondary
PK of MEDI-575 After the First Dose: Dose-normalized Area Under the Serum Concentration-time Curve (AUCτ/Dose)
The AUCτ/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.
Time frame: 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.
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | PK of MEDI-575 After the First Dose: Dose-normalized Area Under the Serum Concentration-time Curve (AUCτ/Dose) | 0.804 μg·day/mL/mg | Standard Deviation 0.0392 |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | PK of MEDI-575 After the First Dose: Dose-normalized Area Under the Serum Concentration-time Curve (AUCτ/Dose) | 1.36 μg·day/mL/mg | Standard Deviation 0.441 |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | PK of MEDI-575 After the First Dose: Dose-normalized Area Under the Serum Concentration-time Curve (AUCτ/Dose) | 1.19 μg·day/mL/mg | Standard Deviation 0.437 |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | PK of MEDI-575 After the First Dose: Dose-normalized Area Under the Serum Concentration-time Curve (AUCτ/Dose) | 2.01 μg·day/mL/mg | Standard Deviation 0.418 |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | PK of MEDI-575 After the First Dose: Dose-normalized Area Under the Serum Concentration-time Curve (AUCτ/Dose) | 2.12 μg·day/mL/mg | Standard Deviation 0.442 |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | PK of MEDI-575 After the First Dose: Dose-normalized Area Under the Serum Concentration-time Curve (AUCτ/Dose) | 2.78 μg·day/mL/mg | Standard Deviation 0.767 |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | PK of MEDI-575 After the First Dose: Dose-normalized Area Under the Serum Concentration-time Curve (AUCτ/Dose) | 2.35 μg·day/mL/mg | Standard Deviation 0.464 |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | PK of MEDI-575 After the First Dose: Dose-normalized Area Under the Serum Concentration-time Curve (AUCτ/Dose) | 0.607 μg·day/mL/mg | Standard Deviation 0.197 |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | PK of MEDI-575 After the First Dose: Dose-normalized Area Under the Serum Concentration-time Curve (AUCτ/Dose) | 1.15 μg·day/mL/mg | Standard Deviation 0.281 |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | PK of MEDI-575 After the First Dose: Dose-normalized Area Under the Serum Concentration-time Curve (AUCτ/Dose) | 2.70 μg·day/mL/mg | Standard Deviation 0.438 |
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.
Time frame: 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.
Population: All the participants who received first dose of MEDI-575 and for whom PK blood samples were collected and evaluated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | PK of MEDI-575 After the First Dose: Dose-normalized Maximum Serum Concentration (Cmax/Dose) | 0.292 μg/mL/mg | Standard Deviation 0.0404 |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | PK of MEDI-575 After the First Dose: Dose-normalized Maximum Serum Concentration (Cmax/Dose) | 0.402 μg/mL/mg | Standard Deviation 0.125 |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | PK of MEDI-575 After the First Dose: Dose-normalized Maximum Serum Concentration (Cmax/Dose) | 0.335 μg/mL/mg | Standard Deviation 0.107 |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | PK of MEDI-575 After the First Dose: Dose-normalized Maximum Serum Concentration (Cmax/Dose) | 0.638 μg/mL/mg | Standard Deviation 0.171 |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | PK of MEDI-575 After the First Dose: Dose-normalized Maximum Serum Concentration (Cmax/Dose) | 0.655 μg/mL/mg | Standard Deviation 0.191 |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | PK of MEDI-575 After the First Dose: Dose-normalized Maximum Serum Concentration (Cmax/Dose) | 0.360 μg/mL/mg | Standard Deviation 0.0908 |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | PK of MEDI-575 After the First Dose: Dose-normalized Maximum Serum Concentration (Cmax/Dose) | 0.259 μg/mL/mg | Standard Deviation 0.0614 |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | PK of MEDI-575 After the First Dose: Dose-normalized Maximum Serum Concentration (Cmax/Dose) | 0.262 μg/mL/mg | Standard Deviation 0.0294 |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | PK of MEDI-575 After the First Dose: Dose-normalized Maximum Serum Concentration (Cmax/Dose) | 0.372 μg/mL/mg | Standard Deviation 0.103 |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | PK of MEDI-575 After the First Dose: Dose-normalized Maximum Serum Concentration (Cmax/Dose) | 0.357 μg/mL/mg | Standard Deviation 0.112 |
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.
Time frame: 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.
Population: All the participants who received first dose of MEDI-575 and for whom PK blood samples were collected and evaluated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | PK of MEDI-575 After the First Dose: Time to Maximum Concentration (Tmax) | 0.0759 Day | Standard Deviation 0.0545 |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | PK of MEDI-575 After the First Dose: Time to Maximum Concentration (Tmax) | 0.0479 Day | Standard Deviation 0.00318 |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | PK of MEDI-575 After the First Dose: Time to Maximum Concentration (Tmax) | 0.0618 Day | Standard Deviation 0.0381 |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | PK of MEDI-575 After the First Dose: Time to Maximum Concentration (Tmax) | 0.130 Day | Standard Deviation 0.142 |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | PK of MEDI-575 After the First Dose: Time to Maximum Concentration (Tmax) | 0.106 Day | Standard Deviation 0.0381 |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | PK of MEDI-575 After the First Dose: Time to Maximum Concentration (Tmax) | 0.227 Day | Standard Deviation 0.142 |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | PK of MEDI-575 After the First Dose: Time to Maximum Concentration (Tmax) | 0.0639 Day | Standard Deviation 0.00139 |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | PK of MEDI-575 After the First Dose: Time to Maximum Concentration (Tmax) | 0.103 Day | Standard Deviation 0.0498 |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | PK of MEDI-575 After the First Dose: Time to Maximum Concentration (Tmax) | 0.139 Day | Standard Deviation 0.0804 |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | PK of MEDI-575 After the First Dose: Time to Maximum Concentration (Tmax) | 0.118 Day | Standard Deviation 0.0941 |
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.
Time frame: 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.
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | PK of MEDI-575 After the First Dose: Trough Serum Concentration (Ctrough) | 8.97 μg/mL | Standard Deviation 2.85 |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | PK of MEDI-575 After the First Dose: Trough Serum Concentration (Ctrough) | 41.5 μg/mL | Standard Deviation 13.8 |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | PK of MEDI-575 After the First Dose: Trough Serum Concentration (Ctrough) | 72.6 μg/mL | Standard Deviation 35.3 |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | PK of MEDI-575 After the First Dose: Trough Serum Concentration (Ctrough) | 144 μg/mL | Standard Deviation 18 |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | PK of MEDI-575 After the First Dose: Trough Serum Concentration (Ctrough) | 199 μg/mL | Standard Deviation 55.3 |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | PK of MEDI-575 After the First Dose: Trough Serum Concentration (Ctrough) | 85.4 μg/mL | Standard Deviation 40.8 |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | PK of MEDI-575 After the First Dose: Trough Serum Concentration (Ctrough) | 223 μg/mL | Standard Deviation 25.2 |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | PK of MEDI-575 After the First Dose: Trough Serum Concentration (Ctrough) | NA μg/mL | — |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | PK of MEDI-575 After the First Dose: Trough Serum Concentration (Ctrough) | 59.0 μg/mL | Standard Deviation 4.14 |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | PK of MEDI-575 After the First Dose: Trough Serum Concentration (Ctrough) | 74.9 μg/mL | Standard Deviation 22.6 |
Secondary
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.
Time frame: 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
Population: Efficacy evaluable population. N= number of participants analyzed for this outcome measure
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Progression-free Survival | 1.8 Months |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Progression-free Survival | 1.4 Months |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Progression-free Survival | 1.2 Months |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Progression-free Survival | 1.4 Months |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Progression-free Survival | 5.0 Months |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Progression-free Survival | 2.9 Months |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Progression-free Survival | 1.2 Months |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Progression-free Survival | 1.4 Months |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Progression-free Survival | 1.3 Months |
Secondary
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.
Time frame: Start of treatment with MEDI-575 until the documentation of disease progression, up to 24 months
Population: Efficacy evaluable population. N= number of participants analyzed for this outcome measure
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Time to Progression | 1.8 Months |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Time to Progression | 1.4 Months |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Time to Progression | 1.2 Months |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Time to Progression | 1.4 Months |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Time to Progression | 5.0 Months |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Time to Progression | 2.9 Months |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Time to Progression | 1.2 Months |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Time to Progression | 1.4 Months |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Time to Progression | 1.3 Months |
Secondary
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.
Population: Efficacy evaluable population with an objective response. Time to response was not estimable as there were no participants with an objective response.