A Phase 1 interventional study of MEDI-573 in Cancer, sponsored by MedImmune LLC. Completed at 6 sites in United States. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2019-03-04.
Sponsored by MedImmune LLC · Phase 1, Interventional, and Treatment
Evaluate the safety and tolerability of MEDI-573 in adult subjects with advanced solid tumors refractory to standard therapy or for which no standard therapy exists.
MedImmune LLC is the lead sponsor of 265 studies on the registry; none are open to participants now.
Of its 50 completed or terminated interventional studies of FDA-regulated products, 28 (56%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants received MEDI-573 0.5 milligram per kilogram (mg/kg) as a 60-minute intravenous (IV) infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
Drug: MEDI-573
Participants received MEDI-573 1.5 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
Drug: MEDI-573
Participants received MEDI-573 5 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
Drug: MEDI-573
Participants received MEDI-573 10 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
Drug: MEDI-573
Participants received MEDI-573 15 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
Drug: MEDI-573
Participants received MEDI-573 30 mg/kg as a 90-minute IV infusion once every 21 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
Drug: MEDI-573
Participants received MEDI-573 45 mg/kg as a 90-minute IV infusion once every 21 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
Drug: MEDI-573
Participants received MEDI-573 5 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
Drug: MEDI-573
Participants received MEDI-573 15 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
Drug: MEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
AEs were any unfavorable and unintended signs (including abnormal laboratory findings), symptoms, or diseases temporally associated with the use of MEDI-573, whether or not considered related to MEDI-573. A SAE was any AE that resulted in: death; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; was life-threatening; was a congenital anomaly/birth defect in the offspring of a study participant; or was an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes above. TEAEs were defined as AEs present at baseline that worsened in intensity after administration of MEDI-573, or events absent at baseline that emerged after administration of MEDI-573, up to 30 days after the last dose.
Time frame: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
An abnormal laboratory finding that was judged by the investigator to be medically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-573, or events absent at baseline that emerged after administration of MEDI-573, for the period extending to 30 days after the last dose.
Time frame: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs
Vital signs and physical findings included parameters such as heart rate, blood pressure, temperature, and respiratory rate. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-573 or events absent at baseline that emerged after administration of MEDI-573, for the period extending to 30 days after the last dose.
Time frame: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
Maximum Tolerated Dose (MTD) of MEDI-573
The MTD was defined as the highest dose that can be safely administered to participants and was determined by the number of participants in each cohort with a dose-limiting toxicity (DLT). The number and proportion of participants in each dose cohort and the number of participants with a DLT was presented using the total number of participants in the MTD Evaluable Population as the denominator. 2 participants from Cohorts 0.5 and 5 mg/kg QWk (1 in each cohort) did not complete the DLT period and therefore not evaluable for MTD.
Time frame: Cycle 1 Day 1 through Cycle 1 Day 21
Number of Participants With Dose-Limiting Toxicities (DLTs)
A DLT was defined as any grade greater than or equal to (\>=) 3 treatment-related non-hematologic toxicity that occurred during the DLT assessment period with the following exceptions: Grade less than (\<) 4 serum-high glucose (fasting) with duration of \< 24 hours; Grade 3 fever (in the absence of neutropenia) defined as \> 40.0 degree centigrade (°C) \[greater than (\>) 104.0°F\] that resolved to normal or baseline within 24 hours of treatment and was not considered an SAE; or Grade 3 rigors/chills that responded to optimal therapy; any Grade \>= 3 treatment-related hematologic toxicity that occurred during the DLT assessment period.
Time frame: Cycle 1 Day 1 through Cycle 1 Day 21
Optimal Biologically Effective Dose (OBED) of MEDI-573
The OBED was defined as the dose at which all circulating insulin-like growth factor (IGF)-1 and IGF-2 ligand was sequestered by MEDI-573.
Time frame: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
Maximum Observed Serum Concentration (Cmax) After the First Dose
The Cmax was the maximum observed serum concentration of MEDI-573.
Time frame: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
Time to Reach Maximum Observed Concentration (Tmax) After the First Dose
The tmax was defined as actual sampling time to reach the maximum observed serum concentration of MEDI-573.
Time frame: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
Trough Serum Concentration (Ctrough) After the First Dose
The Ctrough was the lowest serum concentration of MEDI-573 within a dosing interval.
Time frame: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
Dose Normalized Cmax (Cmax/Dose) After the First Dose
The Cmax/dose was the dose-normalized maximum serum concentration of MEDI-573.
Time frame: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
Area Under the Serum Concentration-time Curve Over the First Dosing Interval (AUCτ)
Area under the serum concentration-time curve over the first dosing interval.
Time frame: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
Dose-normalized Area Under the Serum Concentration Time Curve Over the First Dosing Interval (AUCτ/Dose)
The AUCtau/dose was a measure of dose-normalized area under the serum concentration-time curve over the first dosing interval.
Time frame: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI-573
Two methods were used to assess the immunogenicity data: an ECL-based method and measurement of neutralizing ADA. The titer was calculated by multiplying the minimum assay dilution factor by the reciprocal of the highest dilution factor which yielded an ECL multiple equal to or greater than the screening assay cut-point factor.
Time frame: Pre-infusion on Day 1 of each cycle, end of treatment, and 90 days after last dose MEDI-573 (up to 3.5 years)
Objective Response Rate (ORR)
The ORR was defined as the proportion of participants with confirmed complete response (CR) or partial response (PR) according to the RECIST criteria The CR was defined as disappearance of all target and nontarget lesions and no new lesions; and PR was definded as \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline \[screening\]) and no new lesions.
Time frame: From study entry through the end of the study, up to 3.5 years
Progression-free Survival (PFS)
Progression-free survival (PFS) was defined as the duration from the start of treatment with MEDI-573 until the documentation of disease progression or death due to any cause, whichever occurred first.
Time frame: From study entry through the end of the study, up to 3.5 years
Time to Progression
Time to disease progression (TTP) was defined as the duration from the start of treatment with MEDI-573 until the documentation of disease progression.
Time frame: From study entry through the end of the study, up to 3.5 years
Overall Survival
Overall survival (OS) was defined as the time from the start of treatment with MEDI-573 until death.
Time frame: From study entry through the end of the study, up to 3.5 years
Time to Response (TTR)
Time to response was defined as the duration from the start of treatment with MEDI-573 to the first documentation of objective response (confirmed CR or PR) and was only assessed in participants who had achieved objective response.
Time frame: From study entry through the end of the study, up to 3.5 years
Duration of Response
Duration of response was defined as the duration from the first documentation of objective response (confirmed CR or PR) to the first documented disease progression.
Time frame: From study entry through the end of the study, up to 3.5 years
Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573
The suppression profiles of both IGF-1 and IGF-2 post administration of MEDI-573 in relation to time course of antibody concentrations in serum were evaluated during treatment.
Time frame: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
A total of 43 participants ((23 participants in dose-escalation phase and 20 participants in dose-expansion phase) were entered in the study and received the study treatment.
| Milestone | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Expansion | MEDI-573 15 mg/Kg QWk Dose Expansion |
|---|---|---|---|---|---|---|---|---|---|
| Started | 4 | 3 | 4 | 3 | 3 | 3 | 3 | 10 | 10 |
| Completed | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 1 | 0 |
| Not completed | 4 | 3 | 3 | 3 | 2 | 3 | 3 | 9 | 10 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 2 | 1 |
| Withdrew: Death | 4 | 3 | 3 | 3 | 1 | 1 | 3 | 7 | 8 |
| Withdrew: Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
AEs were any unfavorable and unintended signs (including abnormal laboratory findings), symptoms, or diseases temporally associated with the use of MEDI-573, whether or not considered related to MEDI-573. A SAE was any AE that resulted in: death; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; was life-threatening; was a congenital anomaly/birth defect in the offspring of a study participant; or was an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes above. TEAEs were defined as AEs present at baseline that worsened in intensity after administration of MEDI-573, or events absent at baseline that emerged after administration of MEDI-573, up to 30 days after the last dose.
| Participants | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation |
|---|---|---|---|---|---|---|---|
| TEAEs | 4 | 3 | 13 | 3 | 13 | 3 | 3 |
| Treatment emergent SAEs | 2 | 1 | 4 | 1 | 6 | 0 | 3 |
An abnormal laboratory finding that was judged by the investigator to be medically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-573, or events absent at baseline that emerged after administration of MEDI-573, for the period extending to 30 days after the last dose.
| Participants | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation |
|---|---|---|---|---|---|---|---|
| Anemia | 2 | 1 | 1 | 2 | 2 | 0 | 0 |
| Thrombocytopenia | 0 | 0 | 1 | 2 | 0 | 0 | 0 |
| Leukopenia | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
| Lymphopenia | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Red blood cell count decreased | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| White blood cell count decreased | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| White blood cell count increased | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Blood alkaline phosphatase increased | 1 | 0 | 1 | 1 | 3 | 0 | 1 |
| Aspartate aminotransferase increased | 0 | 1 | 2 | 0 | 2 | 0 | 0 |
| Alanine aminotransferase increased | 0 | 0 | 2 | 0 | 2 | 0 | 0 |
| Blood creatinine increased | 1 | 0 | 1 | 0 | 2 | 0 | 0 |
| Weight decreased | 0 | 0 | 1 | 0 | 2 | 1 | 0 |
| Blood insulin increased | 0 | 1 | 0 | 1 | 1 | 0 | 0 |
| Blood creatine increased | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| Blood growth hormone increased | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
| Blood bilirubin increased | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Blood lactate dehydrogenase increased | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Breath sounds abnormal | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Cardiac enzymes increased | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Electrocardiogram QT prolonged | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Glomerular filtration rate decreased | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Heart rate increased | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Lipase increased | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Protein total increased | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Weight increased | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Hematuria | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Renal failure | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
Vital signs and physical findings included parameters such as heart rate, blood pressure, temperature, and respiratory rate. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-573 or events absent at baseline that emerged after administration of MEDI-573, for the period extending to 30 days after the last dose.
| Participants | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation |
|---|---|---|---|---|---|---|---|
| Pyrexia | 1 | 1 | 1 | 0 | 1 | 0 | 0 |
| Tachycardia | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
| Breath sounds abnormal | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Hypotension | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Heart rate increased | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Hypertension | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Orthostatic hypotension | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
The MTD was defined as the highest dose that can be safely administered to participants and was determined by the number of participants in each cohort with a dose-limiting toxicity (DLT). The number and proportion of participants in each dose cohort and the number of participants with a DLT was presented using the total number of participants in the MTD Evaluable Population as the denominator. 2 participants from Cohorts 0.5 and 5 mg/kg QWk (1 in each cohort) did not complete the DLT period and therefore not evaluable for MTD.
| mg/kg | MEDI-573 Dose Escalation |
|---|---|
| Maximum Tolerated Dose (MTD) of MEDI-573 | NA |
A DLT was defined as any grade greater than or equal to (\>=) 3 treatment-related non-hematologic toxicity that occurred during the DLT assessment period with the following exceptions: Grade less than (\<) 4 serum-high glucose (fasting) with duration of \< 24 hours; Grade 3 fever (in the absence of neutropenia) defined as \> 40.0 degree centigrade (°C) \[greater than (\>) 104.0°F\] that resolved to normal or baseline within 24 hours of treatment and was not considered an SAE; or Grade 3 rigors/chills that responded to optimal therapy; any Grade \>= 3 treatment-related hematologic toxicity that occurred during the DLT assessment period.
| Participants | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation |
|---|---|---|---|---|---|---|---|
| Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
The OBED was defined as the dose at which all circulating insulin-like growth factor (IGF)-1 and IGF-2 ligand was sequestered by MEDI-573.
| mg/kg | MEDI-573 Dose Escalation |
|---|---|
| Optimal Biologically Effective Dose (OBED) of MEDI-573 | 5 |
The Cmax was the maximum observed serum concentration of MEDI-573.
| microgram per milliliter (mcg/mL) | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Expansion | MEDI-573 15 mg/Kg QWk Dose Expansion |
|---|---|---|---|---|---|---|---|---|---|
| Maximum Observed Serum Concentration (Cmax) After the First Dose | 11.6 ± 5.54 | 71.8 ± 12.5 | 166 ± 37.7 | 264 ± 121 | 560 ± 251 | 588 ± 213 | 1200 ± 621 | 115 ± 42.6 | 412 ± 141 |
The tmax was defined as actual sampling time to reach the maximum observed serum concentration of MEDI-573.
| Day | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Expansion | MEDI-573 15 mg/Kg QWk Dose Expansion |
|---|---|---|---|---|---|---|---|---|---|
| Time to Reach Maximum Observed Concentration (Tmax) After the First Dose | 0.04 (0.04 to 0.04) | 0.04 (0.04 to 0.06) | 0.04 (0.04 to 0.12) | 0.04 (0.04 to 0.14) | 0.28 (0.12 to 0.30) | 0.06 (0.06 to 0.06) | 0.06 (0.06 to 0.06) | 0.04 (0.04 to 0.30) | 0.06 (0.04 to 0.30) |
The Ctrough was the lowest serum concentration of MEDI-573 within a dosing interval.
| mcg/mL | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Expansion | MEDI-573 15 mg/Kg QWk Dose Expansion |
|---|---|---|---|---|---|---|---|---|---|
| Trough Serum Concentration (Ctrough) After the First Dose | 1.04 ± 0.919 | 1.98 ± 0.377 | 17.3 ± 10.2 | 34.6 ± 26.8 | 138 ± 77.8 | 32.9 ± 28.2 | 63.5 ± 59.5 | 5.27 ± 4.80 | 77.8 ± 33.5 |
The Cmax/dose was the dose-normalized maximum serum concentration of MEDI-573.
| mcg/mL/mg | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Expansion | MEDI-573 15 mg/Kg QWk Dose Expansion |
|---|---|---|---|---|---|---|---|---|---|
| Dose Normalized Cmax (Cmax/Dose) After the First Dose | 0.319 ± 0.154 | 0.593 ± 0.122 | 0.401 ± 0.054 | 0.393 ± 0.129 | 0.422 ± 0.168 | 0.240 ± 0.072 | 0.352 ± 0.178 | 0.267 ± 0.110 | 0.314 ± 0.095 |
Area under the serum concentration-time curve over the first dosing interval.
| mcg*day/mL | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Expansion | MEDI-573 15 mg/Kg QWk Dose Expansion |
|---|---|---|---|---|---|---|---|---|---|
| Area Under the Serum Concentration-time Curve Over the First Dosing Interval (AUCτ) | 9.59 ± 5.12 | 90.8 ± 18.6 | 431 ± 135 | 631 ± 288 | 1950 ± 917 | 3510 ± 1230 | 5790 ± 3390 | 227 ± 99.8 | 1280 ± 392 |
The AUCtau/dose was a measure of dose-normalized area under the serum concentration-time curve over the first dosing interval.
| mcg*day/mL/mg | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Expansion | MEDI-573 15 mg/Kg QWk Dose Expansion |
|---|---|---|---|---|---|---|---|---|---|
| Dose-normalized Area Under the Serum Concentration Time Curve Over the First Dosing Interval (AUCτ/Dose) | 0.245 ± 0.145 | 0.749 ± 0.176 | 0.962 ± 0.041 | 0.955 ± 0.401 | 1.47 ± 0.624 | 1.46 ± 0.526 | 1.70 ± 0.976 | 0.53 ± 0.233 | 0.981 ± 0.275 |
Two methods were used to assess the immunogenicity data: an ECL-based method and measurement of neutralizing ADA. The titer was calculated by multiplying the minimum assay dilution factor by the reciprocal of the highest dilution factor which yielded an ECL multiple equal to or greater than the screening assay cut-point factor.
| Participants | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Expansion | MEDI-573 15 mg/Kg QWk Dose Expansion |
|---|---|---|---|---|---|---|---|---|---|
| Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI-573 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
The ORR was defined as the proportion of participants with confirmed complete response (CR) or partial response (PR) according to the RECIST criteria The CR was defined as disappearance of all target and nontarget lesions and no new lesions; and PR was definded as \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline \[screening\]) and no new lesions.
| Percentage of Participants | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation |
|---|---|---|---|---|---|---|---|
| Objective Response Rate (ORR) | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Progression-free survival (PFS) was defined as the duration from the start of treatment with MEDI-573 until the documentation of disease progression or death due to any cause, whichever occurred first.
| Months | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation |
|---|---|---|---|---|---|---|---|
| Progression-free Survival (PFS) | 1.0 (0.5 to 1.5) | 2.6 (1.3 to 2.8) | 1.4 (1.2 to 2.8) | 1.5 (0.7 to 4.7) | 1.3 (0.7 to 4.2) | NA (1.2 to NA) | — |
Time to disease progression (TTP) was defined as the duration from the start of treatment with MEDI-573 until the documentation of disease progression.
| Months | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation |
|---|---|---|---|---|---|---|---|
| Time to Progression | 1.0 (0.5 to 1.5) | 2.6 (1.3 to 2.8) | 1.4 (1.2 to 2.8) | 1.5 (0.7 to 4.7) | 1.3 (0.7 to 4.2) | NA (1.2 to NA) | — |
Overall survival (OS) was defined as the time from the start of treatment with MEDI-573 until death.
| Months | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation |
|---|---|---|---|---|---|---|---|
| Overall Survival | 5.3 (2.1 to 8.7) | 13.6 (1.9 to 20.2) | 12.3 (1.4 to 37.3) | 2.5 (1.3 to 8.6) | 4.0 (1.1 to 33.0) | 7.9 (1.4 to 7.9) | 4.7 (4.7 to 4.7) |
Time to response was defined as the duration from the start of treatment with MEDI-573 to the first documentation of objective response (confirmed CR or PR) and was only assessed in participants who had achieved objective response.
No measurements were reported for this outcome.
Duration of response was defined as the duration from the first documentation of objective response (confirmed CR or PR) to the first documented disease progression.
No measurements were reported for this outcome.
The suppression profiles of both IGF-1 and IGF-2 post administration of MEDI-573 in relation to time course of antibody concentrations in serum were evaluated during treatment.
| nanogram per milliliter (ng/ml) | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Expansion | MEDI-573 15 mg/Kg QWk Dose Expansion |
|---|---|---|---|---|---|---|---|---|---|
| IGF-I at 0.000 | 4.014 ± 2.177 | 9.264 ± 7.401 | 4.655 ± 3.437 | 1.721 ± 2.710 | 1.440 ± 0.812 | 2.693 ± 2.855 | 1.925 ± 1.374 | 1.749 ± 0.643 | 2.099 ± 1.128 |
| IGF-I at 0.042 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | — | — | NA ± 0.000 | NA ± 0.000 |
| IGF-I at 0.063 | — | — | — | — | — | NA ± 0.000 | NA ± 0.000 | — | — |
| IGF-I at 0.125 | 0.252 ± 0.111 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | — | — | NA ± 0.000 | NA ± 0.000 |
| IGF-I at 0.292 | 0.345 ± 0.227 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | — | — | NA ± 0.000 | NA ± 0.000 |
| IGF-I at 1.000 | 2.088 ± 0.964 | NA ± 0.000 | 0.215 ± 0.117 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 |
| IGF-I at 7.000 | — | — | — | 0.223 ± 0.115 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | 0.641 ± 0.546 | 0.196 ± 0.078 |
| IGF-I at 7.042 | 0.201 ± 0.087 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | — | — | NA ± 0.000 | NA ± 0.000 |
| IGF-I at 14.000 | — | — | — | 0.232 ± 0.130 | NA ± 0.000 | — | — | 0.360 ± 0.166 | NA ± 0.000 |
| IGF-I at 14.042 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | — | — | NA ± 0.000 | NA ± 0.000 |
| IGF-I at 21.000 | — | — | — | 0.334 ± NA | NA ± 0.000 | 0.265 ± 0.189 | 0.241 ± 0.147 | 0.336 ± 0.177 | NA ± 0.000 |
| IGF-II at 0.000 | 2.773 ± 0.320 | 2.984 ± 1.753 | 2.431 ± 0.139 | 1.879 ± 1.020 | 1.872 ± 0.862 | 2.780 ± 0.694 | 4.093 ± 1.039 | 2.689 ± 0.882 | 2.213 ± 0.752 |
| IGF-II at 0.042 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | — | — | NA ± 0.000 | NA ± 0.000 |
| IGF-II at 0.063 | — | — | — | — | — | NA ± 0.000 | NA ± 0.000 | — | — |
| IGF-II at 0.125 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | — | — | NA ± 0.000 | NA ± 0.000 |
| IGF-II at 0.292 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | — | — | NA ± 0.000 | NA ± 0.000 |
| IGF-II at 1.000 | 1.060 ± 0.828 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 |
| IGF-II at 7.000 | — | — | — | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 |
| IGF-II at 7.042 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | — | — | NA ± 0.000 | NA ± 0.000 |
| IGF-II at 14.000 | — | — | — | NA ± 0.000 | NA ± 0.000 | — | — | NA ± 0.000 | NA ± 0.000 |
| IGF-II at 14.042 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | — | — | NA ± 0.000 | NA ± 0.000 |
| IGF-II at 21.000 | — | — | — | NA ± NA | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 | NA ± 0.000 |
Collected over From start of study drug administration until 30 days after the last dose of study drug, up to 3.5 years. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| MEDI-573 0.5 mg/Kg QWk Dose Escalation | 4/4 (100%) | 2/4 (50%) | 4/4 (100%) |
| MEDI-573 1.5 mg/Kg QWk Dose Escalation | 3/3 (100%) | 1/3 (33.3%) | 3/3 (100%) |
| MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | 10/14 (71.4%) | 4/14 (28.6%) | 13/14 (92.9%) |
| MEDI-573 10 mg/Kg QWk Dose Escalation | 3/3 (100%) | 1/3 (33.3%) | 3/3 (100%) |
| MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | 9/13 (69.2%) | 6/13 (46.2%) | 13/13 (100%) |
| MEDI-573 30 mg/Kg Q3Wk Dose Escalation | 1/3 (33.3%) | 0/3 (0%) | 3/3 (100%) |
| MEDI-573 45 mg/Kg Q3Wk Dose Escalation | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) |
| Event | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation |
|---|---|---|---|---|---|---|---|
| Abdominal distensionGastrointestinal disorders | 0/4 | 0/3 | 0/14 | 0/3 | 0/13 | 0/3 | 1/3 |
| Abdominal painGastrointestinal disorders | 0/4 | 0/3 | 1/14 | 0/3 | 0/13 | 0/3 | 1/3 |
| VomitingGastrointestinal disorders | 0/4 | 0/3 | 0/14 | 0/3 | 0/13 | 0/3 | 1/3 |
| Disease progressionGeneral disorders | 0/4 | 0/3 | 0/14 | 0/3 | 0/13 | 0/3 | 1/3 |
| Musculoskeletal chest painMusculoskeletal and connective tissue disorders | 0/4 | 0/3 | 0/14 | 0/3 | 0/13 | 0/3 | 1/3 |
| Colon cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/4 | 0/3 | 0/14 | 1/3 | 0/13 | 0/3 | 0/3 |
| Neoplasm malignantNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/4 | 1/3 | 0/14 | 0/3 | 0/13 | 0/3 | 0/3 |
| Renal failureRenal and urinary disorders | 0/4 | 0/3 | 0/14 | 0/3 | 1/13 | 0/3 | 1/3 |
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 0/4 | 0/3 | 0/14 | 0/3 | 0/13 | 0/3 | 1/3 |
| FatigueGeneral disorders | 1/4 | 0/3 | 0/14 | 0/3 | 0/13 | 0/3 | 0/3 |
| Event | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation |
|---|---|---|---|---|---|---|---|
| Decreased appetiteMetabolism and nutrition disorders | 3/4 | 1/3 | 1/14 | 2/3 | 8/13 | 1/3 | 3/3 |
| AnaemiaBlood and lymphatic system disorders | 2/4 | 1/3 | 1/14 | 2/3 | 2/13 | 0/3 | 0/3 |
| LeukopeniaBlood and lymphatic system disorders | 0/4 | 0/3 | 0/14 | 2/3 | 0/13 | 0/3 | 0/3 |
| ThrombocytopeniaBlood and lymphatic system disorders | 0/4 | 0/3 | 1/14 | 2/3 | 0/13 | 0/3 | 0/3 |
| Abdominal painGastrointestinal disorders | 1/4 | 0/3 | 2/14 | 0/3 | 3/13 | 2/3 | 0/3 |
| DiarrhoeaGastrointestinal disorders | 1/4 | 1/3 | 2/14 | 0/3 | 3/13 | 1/3 | 2/3 |
| NauseaGastrointestinal disorders | 0/4 | 1/3 | 2/14 | 2/3 | 6/13 | 2/3 | 1/3 |
| StomatitisGastrointestinal disorders | 0/4 | 0/3 | 0/14 | 0/3 | 0/13 | 0/3 | 2/3 |
| VomitingGastrointestinal disorders | 0/4 | 1/3 | 2/14 | 2/3 | 1/13 | 2/3 | 1/3 |
| FatigueGeneral disorders | 0/4 | 1/3 | 3/14 | 2/3 | 8/13 | 1/3 | 2/3 |
Safety Population included all participants who had received any MEDI-573 treatment.
| Age, Continuous(Years) | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation | TOTAL |
|---|---|---|---|---|---|---|---|---|
| Mean | 53.8 ± 12.2 | 67.0 ± 8.7 | 64.5 ± 13.7 | 68.0 ± 13.2 | 61.2 ± 8.6 | 58.3 ± 18.5 | 65.7 ± 4.5 | 62.6 ± 11.5 |
| Sex: Female, Male(Participants) | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation | TOTAL |
|---|---|---|---|---|---|---|---|---|
| Female | 4 | 1 | 4 | 2 | 3 | 2 | 2 | 18 |
| Male | 0 | 2 | 10 | 1 | 10 | 1 | 1 | 25 |
| Ethnicity (NIH/OMB)(Participants) | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation | TOTAL |
|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| Not Hispanic or Latino | 4 | 3 | 14 | 3 | 12 | 3 | 3 | 42 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | MEDI-573 0.5 mg/Kg QWk Dose Escalation | MEDI-573 1.5 mg/Kg QWk Dose Escalation | MEDI-573 5 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 10 mg/Kg QWk Dose Escalation | MEDI-573 15 mg/Kg QWk Dose Escalation and Expansion | MEDI-573 30 mg/Kg Q3Wk Dose Escalation | MEDI-573 45 mg/Kg Q3Wk Dose Escalation | TOTAL |
|---|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 | 3 | 0 | 1 | 4 |
| White | 4 | 3 | 14 | 3 | 10 | 3 | 2 | 39 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
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