Unresectable or Metastatic Hepatocellular Carcinoma (HCC)
Conditions
Keywords
HCC, liver cancer, hepatocellular carcinoma, MEDI-573, anti-IGF
Brief summary
A Phase 1b/2, open-label, randomized study to evaluate MEDI-573 in combination with standard of care in adult subjects with unresectable or metastatic hepatocellular carcinoma (HCC).
Interventions
DRUGMEDI-573 (1 of 3 doses)
MEDI-573, a human immunoglobulin G2 lambda (IgG2λ) monoclonal antibody (MAb), is a dual-targeting human antibody that neutralizes insulin-like growth factor (IGF)-I and IGF-II ligands
DRUGSorafenib
Sorafenib is a tyrosine kinase inhibitor, anti-angiogenic, VEGF inhibitor
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years or minimum age of consent per local regulations at the time of screening * Unresectable or metastatic hepatocellular carcinoma * ECOG Performance Status ≤ 2 * Life expectancy of ≥ 3 months;
Exclusion criteria
* Child-Pugh Score for Cirrhosis Mortality \> 7 points * Prior or current system anti-cancer therapy for HCC, including cytotoxic, biologic, targeted or experimental therapy * Prior local treatment for HCC less than 4 weeks prior to initiating study treatment * Active second malignancy * Major surgery, open biopsy or significant traumatic injury within 4 weeks prior to initiating study treatment * Thrombotic or embolic events within 6 months prior to initiating study treatment * Ongoing pancreatitis * Uncontrolled or refractory ascites * Evidence of ongoing spinal cord compression, known carcinomatous meningitis, or known leptomeningeal carcinomatosis * Hepatic encephalopathy \> Grade 1 * Active brain metastases with exceptions * Poorly controlled diabetes mellitus * Active coronary artery disease * Uncontrolled hypertension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs) | Day 1 to Day 21 of Cycle 1 | The DLT was defined as any Grade 3 or higher hematologic or non-hematologic toxicity considered to be related to MEDI-573 that occurred during the DLT evaluation period (Days 1 to 21 of Cycle 1), with the exceptions of Grade 3 fever (occurred in the absence of neutropenia and resolved to normal or baseline within 24 hours of treatment and was not considered as SAE), Grade 3 rigors/chills that responded to optimal therapy, and Grade \< 4 hyperglycemia that resolved in \< 24 hours. |
| Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months) | An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A serious adverse event (SAE) is an AE that results in death, initial or prolonged inpatient hospitalization, life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or an important medical event. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months). |
| Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months) | An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months). |
| Phase 1b: Number of Participants With Vital Signs Abnormalities Reported as TEAEs | From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months) | An abnormal vital signs that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months). |
| Phase 1b: Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs | From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months) | An abnormal ECG findings that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months). |
| Phase 2: Time to Progression | From Day 1 until documentation of progressive disease (approximately 15 months) | Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b and Phase 2: Maximum Observed Serum Concentration (Cmax) of MEDI-573 for Cycle 1 | Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose) | The Cmax is the maximum observed serum concentration of study drug. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons. |
| Phase 1b and Phase 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI-573 | Predose on Day 1 of every treatment cycle; end of treatment; Days 30, 60 and 90 post treatment; every 3 months post treatrment till end of study (approximately 15 months) | Participants with positive ADA to MEDI-573 are reported in the below table. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons. |
| Phase 1b and Phase 2: Area Under Serum Concentration-time Curve From Time Zero to Day 22 (AUC0-Day22) of MEDI-573 for Cycle 1 | Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose) | Area under the concentration-time curve from time zero to Day 22 is reported. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons. |
| Phase 2: Best Overall Tumor Response | From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months) | Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated. |
| Phase 2: Objective Response Rate | From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months) | Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated. |
| Phase 2: Progression-free Survival (PFS) | From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months) | Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated. |
| Phase 2: Change in Tumor Size | From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months) | Phase 2 part the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated. |
| Phase 1b and Phase 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-573 for Cycle 1 | Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose) | The tmax is defined as actual sampling time to reach maximum observed serum concentration of the study drug. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons. |
Countries
United States
Participant flow
Recruitment details
The study was conducted in the USA.
Pre-assignment details
Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. No participants were randomized in Phase 1b Cohort C part of the study as no dose limiting toxicity was observed in Phase 1b Cohort B.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1b Cohort A Participants received MEDI-573 10 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons. | 3 |
| Phase 1b Cohort B Participants received MEDI-573 45 mg/kg IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons. | 3 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 2 | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Phase 1b Cohort A | Phase 1b Cohort B |
|---|---|---|---|
| Age, Continuous | 66.7 Years STANDARD_DEVIATION 7.4 | 67.7 Years STANDARD_DEVIATION 1.2 | 65.7 Years STANDARD_DEVIATION 11.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 2 / 3 |
| other Total, other adverse events | 3 / 3 | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 | 1 / 3 |
Outcome results
Primary
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).
Time frame: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)
Population: Safety population included all participants who received any amount of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thrombocytopenia | 2 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutropenia | 1 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Anemia | 0 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood bilirubin increased | 2 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lipase increased | 2 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperbilirubinemia | 2 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 2 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypophosphataemia | 1 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypoalbuminaemia | 1 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 1 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Amylase increased | 0 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 1 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 0 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood uric acid increased | 0 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Gamma-glutamyltransferase increased | 1 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypercholesterolaemia | 1 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypocalcaemia | 1 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypoglycaemia | 0 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypomagnesaemia | 1 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hematuria | 0 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Proteinuria | 0 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Amylase increased | 1 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Thrombocytopenia | 2 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypomagnesaemia | 0 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Neutropenia | 1 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood alkaline phosphatase increased | 0 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Anemia | 1 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypocalcaemia | 0 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood bilirubin increased | 2 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood creatinine increased | 1 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Lipase increased | 1 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Proteinuria | 1 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hyperbilirubinemia | 0 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Blood uric acid increased | 1 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Aspartate aminotransferase increased | 0 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypoglycaemia | 1 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypophosphataemia | 1 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Gamma-glutamyltransferase increased | 0 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypoalbuminaemia | 1 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hematuria | 1 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | Hypercholesterolaemia | 0 Participants |
Primary
Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)
The DLT was defined as any Grade 3 or higher hematologic or non-hematologic toxicity considered to be related to MEDI-573 that occurred during the DLT evaluation period (Days 1 to 21 of Cycle 1), with the exceptions of Grade 3 fever (occurred in the absence of neutropenia and resolved to normal or baseline within 24 hours of treatment and was not considered as SAE), Grade 3 rigors/chills that responded to optimal therapy, and Grade \< 4 hyperglycemia that resolved in \< 24 hours.
Time frame: Day 1 to Day 21 of Cycle 1
Population: Evaluable population included all participants enrolled in the Phase 1b who received at least 1 full dose of MEDI-573, received sorafenib treatment per standard practice during the DLT evaluation period, and completed safety follow-up through the DLT evaluation period or experienced any DLTs during the DLT evaluation period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b Cohort A | Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs) | 1 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs) | 0 Participants |
Primary
Phase 1b: Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs
An abnormal ECG findings that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).
Time frame: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)
Population: Safety population included all participants who received any amount of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b Cohort A | Phase 1b: Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs | 0 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs | 0 Participants |
Primary
Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A serious adverse event (SAE) is an AE that results in death, initial or prolonged inpatient hospitalization, life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or an important medical event. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).
Time frame: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)
Population: Safety population included all participants who received any amount of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b Cohort A | Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Any TEAEs | 3 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Any TESAEs | 1 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Any TEAEs | 3 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Any TESAEs | 1 Participants |
Primary
Phase 1b: Number of Participants With Vital Signs Abnormalities Reported as TEAEs
An abnormal vital signs that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).
Time frame: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)
Population: Safety population included all participants who received any amount of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b Cohort A | Phase 1b: Number of Participants With Vital Signs Abnormalities Reported as TEAEs | Hypertension | 0 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Vital Signs Abnormalities Reported as TEAEs | Pyrexia | 0 Participants |
| Phase 1b Cohort A | Phase 1b: Number of Participants With Vital Signs Abnormalities Reported as TEAEs | Diastolic hypertension | 0 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Vital Signs Abnormalities Reported as TEAEs | Hypertension | 2 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Vital Signs Abnormalities Reported as TEAEs | Pyrexia | 1 Participants |
| Phase 1b Cohort B | Phase 1b: Number of Participants With Vital Signs Abnormalities Reported as TEAEs | Diastolic hypertension | 1 Participants |
Primary
Phase 2: Time to Progression
Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
Time frame: From Day 1 until documentation of progressive disease (approximately 15 months)
Population: Safety population included all participants who received any amount of study treatment.
Secondary
Phase 1b and Phase 2: Area Under Serum Concentration-time Curve From Time Zero to Day 22 (AUC0-Day22) of MEDI-573 for Cycle 1
Area under the concentration-time curve from time zero to Day 22 is reported. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons.
Time frame: Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose)
Population: Safety population included all participants who received any amount of study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1b Cohort A | Phase 1b and Phase 2: Area Under Serum Concentration-time Curve From Time Zero to Day 22 (AUC0-Day22) of MEDI-573 for Cycle 1 | 887 day*mcg/mL | Standard Deviation 231 |
| Phase 1b Cohort B | Phase 1b and Phase 2: Area Under Serum Concentration-time Curve From Time Zero to Day 22 (AUC0-Day22) of MEDI-573 for Cycle 1 | 6390 day*mcg/mL | Standard Deviation 1440 |
Secondary
Phase 1b and Phase 2: Maximum Observed Serum Concentration (Cmax) of MEDI-573 for Cycle 1
The Cmax is the maximum observed serum concentration of study drug. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons.
Time frame: Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose)
Population: Safety population included all participants who received any amount of study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1b Cohort A | Phase 1b and Phase 2: Maximum Observed Serum Concentration (Cmax) of MEDI-573 for Cycle 1 | 195 mcg/mL | Standard Deviation 11.4 |
| Phase 1b Cohort B | Phase 1b and Phase 2: Maximum Observed Serum Concentration (Cmax) of MEDI-573 for Cycle 1 | 920 mcg/mL | Standard Deviation 145 |
Secondary
Phase 1b and Phase 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI-573
Participants with positive ADA to MEDI-573 are reported in the below table. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons.
Time frame: Predose on Day 1 of every treatment cycle; end of treatment; Days 30, 60 and 90 post treatment; every 3 months post treatrment till end of study (approximately 15 months)
Population: Safety population included all participants who received any amount of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b Cohort A | Phase 1b and Phase 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI-573 | 0 Participants |
| Phase 1b Cohort B | Phase 1b and Phase 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI-573 | 0 Participants |
Secondary
Phase 1b and Phase 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-573 for Cycle 1
The tmax is defined as actual sampling time to reach maximum observed serum concentration of the study drug. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons.
Time frame: Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose)
Population: Safety population included all participants who received any amount of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b Cohort A | Phase 1b and Phase 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-573 for Cycle 1 | 1.05 Hours |
| Phase 1b Cohort B | Phase 1b and Phase 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-573 for Cycle 1 | 1.55 Hours |
Secondary
Phase 2: Best Overall Tumor Response
Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
Time frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)
Population: Safety population included all participants who received any amount of study treatment.
Secondary
Phase 2: Change in Tumor Size
Phase 2 part the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
Time frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)
Population: Safety population included all participants who received any amount of study treatment.
Secondary
Phase 2: Objective Response Rate
Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
Time frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)
Population: Safety population included all participants who received any amount of study treatment.
Secondary
Phase 2: Progression-free Survival (PFS)
Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
Time frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)
Population: Safety population included all participants who received any amount of study treatment.