Solid Tumors
Conditions
Keywords
Cancer
Brief summary
This is a first-time-in-human, Phase 1, multicenter, open-label, single-arm, dose-escalation (3+3) study to evaluate the safety, tolerability, antitumor activity, PK and immunogenicity of MEDI0639.
Detailed description
This is a first-time-in-human, Phase 1, multicenter, open-label, single-arm, dose-escalation (3+3) study to evaluate the safety, tolerability, antitumor activity, PK, and immunogenicity of MEDI0639 in adult subjects with advanced solid tumors refractory to standard therapy or for which no standard therapy exist. Up to 63 subjects will be enrolled at approximately 3 to 5 study centers in North America.
Interventions
BIOLOGICALMEDI0639
MEDI0639 is an immunoglobulin G1 lambda (IgG1λ) monoclonal antibody. MEDI0639 selectively binds to DLL4 and blocks its ability to bind to and activate signaling through the Notch receptors.
Sponsors
MedImmune LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed solid tumors that are refractory to standard therapy or for which no standard therapy exist * Age ≥ 18 years * ECOG Performance Status of 0 or 1 * LVEF (measured by Echocardiogram) \> 50% * No gastrointestinal bleeding within 1 year of study entry. * Adequate organ and marrow function: * Hemoglobin ≥ 10g/dL * Absolute Neutrophil Count ≥ 1500/mm3 * Platelet Count ≥ 100,000/mm3 * AST & ALT ≤ 2.5 x ULN * Bilirubin ≤ 1.5 x ULN * Cr Cl ≥ 50 mL/min (as determined by the Cockcroft-Gault equation or by 24-hour urine collection) * Prior therapy against VEGF or VEGFRs including, but not limited to bevacizumab, sunitinib, sorafenib, pazopanib, motesanib (AMG706), or cediranib (AZD2171), is permitted so long as the agent does not have any known activity against DLL4 and the last dose received s at least 6 weeks prior to first dose of MEDI0639. * Life expectancy ≥ 12 weeks * Females of childbearing potential must be surgically sterile, have a sterile male partner, be premenarchal or at least 2 years postmenopausal, practice abstinence or otherwise must use 2 effective methods of contraception from the time of initiation of investigational product. * Males, unless surgically sterile, must use 2 effective methods of contraception with a female partner and must agree to continue using such contraception for 90 days after the last dose of MEDI0639
Exclusion criteria
* Concurrent enrollment in another investigational clinical study * Receipt of any investigational anticancer therapy within 4 weeks prior to the first dose of MEDI0639 or in the case of monoclonal antibodies, 6 weeks prior to the first dose of MEDI0639 * Concurrent or previous treatment with inhibitors of DLL4 * Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment * Known bleeding diathesis, esophageal varices, or angioplasty * Pulmonary hemorrhage or gross hemoptysis within 12 months * Known arterial or venous thrombosis or pulmonary embolism within 2 years * Concurrent use of systemic low molecular weight heparin or low dose warfarin * Presence of brain metastases * Cerebrovascular accident or transient ischemic attack within 2 years * Cardiovascular events, such as myocardial infarction, unstable/severe angina, coronary/peripheral artery bypass graft, unstable cardiac arrhythmia requiring medication, congestive heart failure (NYHA \> class II), within 2 years * Tumors with squamous cell histology * Major surgical procedure within 90 days * Pregnancy or lactation * Known HIV positive or Hepatitis A, B, or C infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of MEDI0639 | From the first dose of MEDI0639 to 21 days after the first dose | The MTD evaluation was based on the dose-limiting toxicity (DLT) evaluable population. DLT is defined as any Grade 3 or higher treatment-related toxicity that occurred during the DLT evaluation period (defined as the time from the first dose of MEDI0639 to 21 days after the first dose), except for National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 hypertension that could be controlled within 96 hours; Grade 3 symptomatic hypertension of greater than (\>) 180 millimetre of mercury (mm Hg) systolic or \>120 mm Hg diastolic or asymptomatic hypertension of \>200 mm Hg systolic or \>120 mm Hg diastolic was considered a DLT. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From the first dose of MEDI0639 until 90 days after the last dose of MEDI0639. Maximum time frame across participants was 11 months. | An adverse event (AE) is any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug. Treatment-emergent AEs (TEAEs) were 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 90 days after the last dose of study drug. The AEs were summarized using Medical Dictionary for Regulatory Activities (MedDRA) version 18.1. |
| Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) | From the first dose of MEDI0639 until the end of participation in the study. Maximum time frame across participants was 4 years. | A serious AE (SAE) is any AE that results in death (refers to an event, which risk of death at the time of the event; it does not refer to an event that may have led to 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 defined as SAEs present at baseline that worsened in intensity after administration of study drug or SAEs absent at baseline that emerged after administration of study drug. The SAEs were summarized using MedDRA version 18.1. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months. | Laboratory evaluations of blood and urine samples were performed, including hematology (white blood cell \[WBC\] count with differential, red blood cell \[RBC\] count, hematocrit, hemoglobin, platelet count, mean corpuscular volume \[MCV\], and mean corpuscular hemoglobin concentration \[MCHC\]); serum chemistry (calcium, chloride, magnesium, potassium, sodium, bicarbonate, aspartate transaminase \[AST\], alanine transaminase \[ALT\], alkaline phosphatase, total bilirubin, liver function test, gamma glutamyl transferase \[GGT\], lactate dehydrogenase, uric acid, creatinine, blood urea nitrogen \[BUN\], glucose, albumin, total protein, triglycerides, cholesterol, and troponin); and routine urinalysis. The TEAEs related to laboratory evaluations in participants were reported. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months. | Vital signs (temperature, blood pressure, pulse rate, and respiratory rate) were performed at baseline and throughout the study. The TEAEs related to vital signs in participants were reported. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months. | ECG parameters included QT interval and corrected QT (QTc) interval. Electrocardiogram (ECG) parameters were assessed at baseline as well as throughout the study. All 12-lead ECGs performed during the study were obtained in triplicate. The TEAEs related to ECG evaluations in participants were reported. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Echocardiogram Evaluations | From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months. | Echocardiogram parameters included left ventricular ejection fraction (LVEF) and pulmonary arterial pressure (PAP). The TEAEs related to echocardiogram evaluations in participants were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Disease Control | From study entry through the end of the study. Maximum time frame across participants was 4 years. | Disease control rate (DCR) defined as the percentage of participants with a BOR of confirmed CR, confirmed PR or SD. |
| Time to Response | From study entry through the end of the study. Maximum time frame across participants was 4 years. | Time to response (TTR) defined as the time from the first dose of MEDI0639 until the first documentation of a subsequently confirmed objective response. Only participants who have achieved objective response (confirmed CR or confirmed PR) was evaluated for TTR. TTR (months) = (Date of first disease response - Date of the first dose of MEDI0639 + 1) / (365.25/12). |
| Maximum Observed Concentration (Cmax) After Cycle 1 Treatment Administration of MEDI0639 | Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1 | The pharmacokinetics (PK) parameter was estimated using the noncompartmental analysis methods, based on the individual serum concentration-time data. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI0639. |
| Progression-free Survival (PFS) | From study entry through the end of the study. Maximum time frame across participants was 4 years. | Progression-free survival (PFS) is defined as the time from the first dose of MEDI0639 until the first documentation of disease progression or death due to any cause, whichever occurs first. PFS (months) = (Date of PD/death or censoring - Date of the first dose of MEDI0639 + 1) / (365.25/12). |
| Overall Survival | From study entry through the end of the study. Maximum time frame across participants was 4 years. | Overall survival defined as the time from the first dose of MEDI0639 until death due to any cause. OS (months) = (Date of death or censoring - Date of the first dose of MEDI0639 + 1) / (365.25/12). |
| Duration of Response (DR) | From study entry through the end of the study. Maximum time frame across participants was 4 years. | DR defined as time from start of first documented objective response \[confirmed Complete Response (CR) or confirmed Partial Response (PR)\] to first documented disease progression or death due to any cause, whichever occurs first. DR calculated as (months) = (Date of PD/death or censoring - Date of first disease response + 1)/ (365.25/12). |
| Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) After Cycle 1 Treatment Administration of MEDI0639 | Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1 | The pharmacokinetics (PK) parameter was estimated using the noncompartmental analysis methods, based on the individual serum concentration-time data. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI0639. |
| Clearance (CL) After Cycle 1 Treatment Administration of MEDI0639 | Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1 | The pharmacokinetics (PK) parameter was estimated using the noncompartmental analysis methods, based on the individual serum concentration-time data. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI0639. Clearance was estimated as dose divided by the area under serum concentration-time curve from time zero to infinity. |
| Half-life (t1/2) After Cycle 1 Treatment Administration of MEDI0639 | Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1 | The pharmacokinetics (PK) parameter was estimated using the noncompartmental analysis methods, based on the individual serum concentration-time data. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI0639. |
| Number of Participants Positive With Antidrug Antibodies (ADA) for MEDI0639 | On Day 1 of Cycles 1, 2, 3, and every other cycle thereafter, end of treatment, 30 days, and 3 and 6 months after the last dose of MEDI0639. Maximum time frame across participants was 14 months. | Blood samples were measured for the presence of ADA for MEDI0639 using a validated bridging immunoassay. Only the number of participants positive for anti-MEDI-575 antibodies at any visit were presented. |
| Percentage of Participants With Best Overall Response | From study entry through the end of the study. Maximum time frame across participants was 4 years. | Percentage (%) of participants who were responders with BOR documented as confirmed CR, PR, stable disease (SD), progressive disease (PD) and non-evaluable (NE). CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 mm. PR: At least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. |
| Percentage of Participants With Objective Response | From study entry through the end of the study. Maximum time frame across participants was 4 years. | Objective response rate (ORR) defined as the percentage of participants with a BOR of confirmed CR or confirmed PR. |
Countries
United States
Participant flow
Recruitment details
A total of 58 participants were screened at 7 sites in the United States of America (USA).
Pre-assignment details
A total of 58 participants were screened for this study, of which 25 participants were enrolled and received study treatment.
Participants by arm
| Arm | Count |
|---|---|
| MEDI0639 Cohort 1 Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | 3 |
| MEDI0639 Cohort 2 Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | 3 |
| MEDI0639 Cohort 3 Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | 3 |
| MEDI0639 Cohort 4 Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | 6 |
| MEDI0639 Cohort 5 Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | 5 |
| MEDI0639 Cohort 6 Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21 day cycle. | 5 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Alternative Therapy | 0 | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Death | 3 | 2 | 2 | 1 | 1 | 3 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 3 | 2 | 0 |
Baseline characteristics
| Characteristic | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 55.7 Years STANDARD_DEVIATION 14 | 57.3 Years STANDARD_DEVIATION 22.5 | 67.7 Years STANDARD_DEVIATION 13.7 | 62.2 Years STANDARD_DEVIATION 9.3 | 62.2 Years STANDARD_DEVIATION 5.2 | 62.6 Years STANDARD_DEVIATION 10.8 | 61.6 Years STANDARD_DEVIATION 11.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 3 Participants | 6 Participants | 4 Participants | 5 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 3 Participants | 6 Participants | 5 Participants | 5 Participants | 24 Participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 13 Participants |
| Sex: Female, Male Male | 3 Participants | 0 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 12 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 6 / 6 | 5 / 5 | 4 / 5 |
| serious Total, serious adverse events | 2 / 3 | 1 / 3 | 2 / 3 | 2 / 6 | 4 / 5 | 3 / 5 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of MEDI0639
The MTD evaluation was based on the dose-limiting toxicity (DLT) evaluable population. DLT is defined as any Grade 3 or higher treatment-related toxicity that occurred during the DLT evaluation period (defined as the time from the first dose of MEDI0639 to 21 days after the first dose), except for National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 hypertension that could be controlled within 96 hours; Grade 3 symptomatic hypertension of greater than (\>) 180 millimetre of mercury (mm Hg) systolic or \>120 mm Hg diastolic or asymptomatic hypertension of \>200 mm Hg systolic or \>120 mm Hg diastolic was considered a DLT.
Time frame: From the first dose of MEDI0639 to 21 days after the first dose
Population: All participants enrolled in the dose-escalation phase who received at least 1 full cycle of MEDI0639 and completed safety follow-up through the DLT evaluation period or experienced any DLT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI0639 | Maximum Tolerated Dose (MTD) of MEDI0639 | NA milligram (mg) |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug. Treatment-emergent AEs (TEAEs) were 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 90 days after the last dose of study drug. The AEs were summarized using Medical Dictionary for Regulatory Activities (MedDRA) version 18.1.
Time frame: From the first dose of MEDI0639 until 90 days after the last dose of MEDI0639. Maximum time frame across participants was 11 months.
Population: All participants who received at least one dose of MEDI0639.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 5 participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 5 participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Echocardiogram Evaluations
Echocardiogram parameters included left ventricular ejection fraction (LVEF) and pulmonary arterial pressure (PAP). The TEAEs related to echocardiogram evaluations in participants were reported.
Time frame: From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months.
Population: All participants who received at least one dose of MEDI0639.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Echocardiogram Evaluations | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Echocardiogram Evaluations | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Echocardiogram Evaluations | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Echocardiogram Evaluations | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Echocardiogram Evaluations | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Echocardiogram Evaluations | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations
ECG parameters included QT interval and corrected QT (QTc) interval. Electrocardiogram (ECG) parameters were assessed at baseline as well as throughout the study. All 12-lead ECGs performed during the study were obtained in triplicate. The TEAEs related to ECG evaluations in participants were reported.
Time frame: From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months.
Population: All participants who received at least one dose of MEDI0639.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Atrioventricular block first degree | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Electrocardiogram t wave amplitude decreased | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | ECG QT prolonged | 1 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Electrocardiogram ST-T change | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Atrial fibrillation | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Electrocardiogram t wave amplitude decreased | 1 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Atrioventricular block first degree | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | ECG QT prolonged | 1 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Electrocardiogram ST-T change | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Atrial fibrillation | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Electrocardiogram t wave amplitude decreased | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Atrioventricular block first degree | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Electrocardiogram ST-T change | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Atrial fibrillation | 1 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | ECG QT prolonged | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Atrial fibrillation | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | ECG QT prolonged | 2 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Electrocardiogram t wave amplitude decreased | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Atrioventricular block first degree | 1 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Electrocardiogram ST-T change | 1 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Atrioventricular block first degree | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | ECG QT prolonged | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Electrocardiogram ST-T change | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Electrocardiogram t wave amplitude decreased | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Atrial fibrillation | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | ECG QT prolonged | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Atrioventricular block first degree | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Electrocardiogram t wave amplitude decreased | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Electrocardiogram ST-T change | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations | Atrial fibrillation | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters
Laboratory evaluations of blood and urine samples were performed, including hematology (white blood cell \[WBC\] count with differential, red blood cell \[RBC\] count, hematocrit, hemoglobin, platelet count, mean corpuscular volume \[MCV\], and mean corpuscular hemoglobin concentration \[MCHC\]); serum chemistry (calcium, chloride, magnesium, potassium, sodium, bicarbonate, aspartate transaminase \[AST\], alanine transaminase \[ALT\], alkaline phosphatase, total bilirubin, liver function test, gamma glutamyl transferase \[GGT\], lactate dehydrogenase, uric acid, creatinine, blood urea nitrogen \[BUN\], glucose, albumin, total protein, triglycerides, cholesterol, and troponin); and routine urinalysis. The TEAEs related to laboratory evaluations in participants were reported.
Time frame: From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months.
Population: All participants who received at least one dose of MEDI0639.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Proteinuria | 1 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | WBC urine positive | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Alanine aminotransferase increased | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperbilirubinaemia | 1 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood creatinine increased | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | N-terminal prohormone BNP increased | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Leukocytosis | 1 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypophosphataemia | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Aspartate aminotransferase increased | 1 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Dyslipidaemia | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyponatraemia | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Anaemia | 2 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hepatobiliary disorders | 1 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Gamma-glutamyltransferase increased | 3 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood alkaline phosphatase increased | 1 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypomagnesaemia | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood cholesterol increased | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypernatraemia | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypertriglyceridaemia | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood bilirubin increased | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Brain natriuretic peptide increased | 1 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperuricaemia | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypercalcaemia | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Lymphopenia | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood triglycerides increased | 1 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | White blood cell count decreased | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Thrombocytopenia | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypoalbuminaemia | 1 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypercholesterolaemia | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Troponin increased | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Leukopenia | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Metabolism and nutrition disorders | 2 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Neutropenia | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypoglycaemia | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperglycaemia | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypokalaemia | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypocalcaemia | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood lactate dehydrogenase increased | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Troponin I increased | 2 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperphosphataemia | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperkalaemia | 1 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hepatobiliary disorders | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Lymphopenia | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperbilirubinaemia | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Metabolism and nutrition disorders | 3 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Thrombocytopenia | 1 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Dyslipidaemia | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypercalcaemia | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | WBC urine positive | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypoglycaemia | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypercholesterolaemia | 1 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | White blood cell count decreased | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperglycaemia | 1 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Neutropenia | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypophosphataemia | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Alanine aminotransferase increased | 1 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperphosphataemia | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Aspartate aminotransferase increased | 2 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Leukocytosis | 1 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Proteinuria | 1 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood alkaline phosphatase increased | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood bilirubin increased | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypocalcaemia | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyponatraemia | 1 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood cholesterol increased | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypertriglyceridaemia | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood creatinine increased | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypernatraemia | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood lactate dehydrogenase increased | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood triglycerides increased | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Leukopenia | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypomagnesaemia | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Brain natriuretic peptide increased | 1 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperuricaemia | 1 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Gamma-glutamyltransferase increased | 1 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperkalaemia | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | N-terminal prohormone BNP increased | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Anaemia | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Troponin I increased | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypokalaemia | 1 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Troponin increased | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypoalbuminaemia | 1 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperglycaemia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypercholesterolaemia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypomagnesaemia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypercalcaemia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperbilirubinaemia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood triglycerides increased | 1 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Proteinuria | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Troponin I increased | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperkalaemia | 1 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Anaemia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | WBC urine positive | 1 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Brain natriuretic peptide increased | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hepatobiliary disorders | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Leukopenia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypocalcaemia | 1 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Dyslipidaemia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Thrombocytopenia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Gamma-glutamyltransferase increased | 2 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperuricaemia | 1 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypernatraemia | 1 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyponatraemia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypoalbuminaemia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood bilirubin increased | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypoglycaemia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Leukocytosis | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Troponin increased | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood alkaline phosphatase increased | 2 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | N-terminal prohormone BNP increased | 1 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood cholesterol increased | 1 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Neutropenia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperphosphataemia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Aspartate aminotransferase increased | 2 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Alanine aminotransferase increased | 2 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Lymphopenia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood creatinine increased | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypertriglyceridaemia | 1 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypokalaemia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypophosphataemia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | White blood cell count decreased | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Metabolism and nutrition disorders | 3 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood lactate dehydrogenase increased | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypokalaemia | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperkalaemia | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypernatraemia | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Neutropenia | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperphosphataemia | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Anaemia | 3 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypertriglyceridaemia | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperuricaemia | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypoalbuminaemia | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Thrombocytopenia | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypophosphataemia | 1 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | White blood cell count decreased | 1 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Alanine aminotransferase increased | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Aspartate aminotransferase increased | 1 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyponatraemia | 1 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood alkaline phosphatase increased | 2 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood bilirubin increased | 1 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Leukocytosis | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood cholesterol increased | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood creatinine increased | 1 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | WBC urine positive | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypomagnesaemia | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood lactate dehydrogenase increased | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood triglycerides increased | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Brain natriuretic peptide increased | 2 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Gamma-glutamyltransferase increased | 2 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Leukopenia | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | N-terminal prohormone BNP increased | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Troponin I increased | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Troponin increased | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Proteinuria | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hepatobiliary disorders | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperbilirubinaemia | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypoglycaemia | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Metabolism and nutrition disorders | 3 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Lymphopenia | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Dyslipidaemia | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypercalcaemia | 1 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypercholesterolaemia | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperglycaemia | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypocalcaemia | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypertriglyceridaemia | 1 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Anaemia | 3 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Leukocytosis | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Leukopenia | 1 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Lymphopenia | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Neutropenia | 1 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Thrombocytopenia | 1 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | White blood cell count decreased | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Alanine aminotransferase increased | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Aspartate aminotransferase increased | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood alkaline phosphatase increased | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood bilirubin increased | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood cholesterol increased | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood creatinine increased | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood lactate dehydrogenase increased | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood triglycerides increased | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Brain natriuretic peptide increased | 2 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Gamma-glutamyltransferase increased | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | N-terminal prohormone BNP increased | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Troponin I increased | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Troponin increased | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hepatobiliary disorders | 1 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperbilirubinaemia | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Metabolism and nutrition disorders | 3 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Dyslipidaemia | 1 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypercalcaemia | 1 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypercholesterolaemia | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperglycaemia | 1 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperkalaemia | 1 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypernatraemia | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperphosphataemia | 1 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperuricaemia | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypoalbuminaemia | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypocalcaemia | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypoglycaemia | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypokalaemia | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Proteinuria | 1 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypomagnesaemia | 1 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyponatraemia | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypophosphataemia | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | WBC urine positive | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypocalcaemia | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypercholesterolaemia | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypercalcaemia | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Dyslipidaemia | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Metabolism and nutrition disorders | 2 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperbilirubinaemia | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Lymphopenia | 2 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypoglycaemia | 1 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hepatobiliary disorders | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Troponin increased | 1 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Troponin I increased | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | N-terminal prohormone BNP increased | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Gamma-glutamyltransferase increased | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Leukopenia | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypokalaemia | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Brain natriuretic peptide increased | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood triglycerides increased | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Leukocytosis | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood lactate dehydrogenase increased | 1 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood creatinine increased | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Proteinuria | 1 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypomagnesaemia | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood cholesterol increased | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood bilirubin increased | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Blood alkaline phosphatase increased | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Aspartate aminotransferase increased | 2 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | WBC urine positive | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyponatraemia | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Alanine aminotransferase increased | 1 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | White blood cell count decreased | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Thrombocytopenia | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Anaemia | 1 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperuricaemia | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypophosphataemia | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypoalbuminaemia | 1 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypertriglyceridaemia | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperphosphataemia | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hypernatraemia | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperkalaemia | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Hyperglycaemia | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters | Neutropenia | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination
Vital signs (temperature, blood pressure, pulse rate, and respiratory rate) were performed at baseline and throughout the study. The TEAEs related to vital signs in participants were reported.
Time frame: From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months.
Population: All participants who received at least one dose of MEDI0639.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Hypotension | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Electrocardiogram t wave amplitude decreased | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Sinus tachycardia | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Electrocardiogram ST-T change | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Atrioventricular block first degree | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Hypertension | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Weight decreased | 1 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Electrocardiogram QT prolonged | 1 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Atrial fibrillation | 0 Participants |
| MEDI0639 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Pyrexia | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Weight decreased | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Electrocardiogram QT prolonged | 1 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Electrocardiogram t wave amplitude decreased | 1 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Hypotension | 1 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Pyrexia | 2 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Atrial fibrillation | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Hypertension | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Atrioventricular block first degree | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Electrocardiogram ST-T change | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Sinus tachycardia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Hypotension | 1 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Atrioventricular block first degree | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Electrocardiogram QT prolonged | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Pyrexia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Electrocardiogram t wave amplitude decreased | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Weight decreased | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Atrial fibrillation | 1 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Electrocardiogram ST-T change | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Sinus tachycardia | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Hypertension | 1 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Hypertension | 2 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Atrioventricular block first degree | 1 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Weight decreased | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Sinus tachycardia | 1 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Electrocardiogram ST-T change | 1 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Electrocardiogram QT prolonged | 2 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Atrial fibrillation | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Pyrexia | 2 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Hypotension | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Electrocardiogram t wave amplitude decreased | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Hypertension | 1 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Hypotension | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Pyrexia | 2 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Atrial fibrillation | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Electrocardiogram QT prolonged | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Atrioventricular block first degree | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Sinus tachycardia | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Electrocardiogram ST-T change | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Electrocardiogram t wave amplitude decreased | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Weight decreased | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Atrial fibrillation | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Sinus tachycardia | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Weight decreased | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Electrocardiogram t wave amplitude decreased | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Pyrexia | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Hypertension | 1 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Hypotension | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Atrioventricular block first degree | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Electrocardiogram QT prolonged | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination | Electrocardiogram ST-T change | 0 Participants |
Primary
Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
A serious AE (SAE) is any AE that results in death (refers to an event, which risk of death at the time of the event; it does not refer to an event that may have led to 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 defined as SAEs present at baseline that worsened in intensity after administration of study drug or SAEs absent at baseline that emerged after administration of study drug. The SAEs were summarized using MedDRA version 18.1.
Time frame: From the first dose of MEDI0639 until the end of participation in the study. Maximum time frame across participants was 4 years.
Population: All participants who received at least one dose of MEDI0639.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI0639 | Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) | 2 Participants |
| MEDI0639 Cohort 2 | Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) | 1 Participants |
| MEDI0639 Cohort 3 | Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) | 2 Participants |
| MEDI0639 Cohort 4 | Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) | 2 Participants |
| MEDI0639 Cohort 5 | Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) | 4 Participants |
| MEDI0639 Cohort 6 | Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) | 3 Participants |
Secondary
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) After Cycle 1 Treatment Administration of MEDI0639
The pharmacokinetics (PK) parameter was estimated using the noncompartmental analysis methods, based on the individual serum concentration-time data. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI0639.
Time frame: Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1
Population: All the participants who received dose of MEDI0639 in Cycle 1 and for whom Pharmacokinetic (PK) blood samples were collected and evaluated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI0639 | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) After Cycle 1 Treatment Administration of MEDI0639 | 7.41 microgram*day per milliliter (mcg*d/mL) | Standard Deviation 1.04 |
| MEDI0639 Cohort 2 | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) After Cycle 1 Treatment Administration of MEDI0639 | 41.1 microgram*day per milliliter (mcg*d/mL) | Standard Deviation 34 |
| MEDI0639 Cohort 3 | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) After Cycle 1 Treatment Administration of MEDI0639 | 89.9 microgram*day per milliliter (mcg*d/mL) | Standard Deviation 64.9 |
| MEDI0639 Cohort 4 | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) After Cycle 1 Treatment Administration of MEDI0639 | 179 microgram*day per milliliter (mcg*d/mL) | Standard Deviation 59.9 |
| MEDI0639 Cohort 5 | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) After Cycle 1 Treatment Administration of MEDI0639 | 434 microgram*day per milliliter (mcg*d/mL) | Standard Deviation 91.9 |
| MEDI0639 Cohort 6 | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) After Cycle 1 Treatment Administration of MEDI0639 | 512 microgram*day per milliliter (mcg*d/mL) | Standard Deviation 250 |
Secondary
Clearance (CL) After Cycle 1 Treatment Administration of MEDI0639
The pharmacokinetics (PK) parameter was estimated using the noncompartmental analysis methods, based on the individual serum concentration-time data. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI0639. Clearance was estimated as dose divided by the area under serum concentration-time curve from time zero to infinity.
Time frame: Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1
Population: All the participants who received dose of MEDI0639 in Cycle 1 and for whom PK blood samples were collected and evaluated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI0639 | Clearance (CL) After Cycle 1 Treatment Administration of MEDI0639 | 1.37 Liter per day (L/d) | Standard Deviation 0.182 |
| MEDI0639 Cohort 2 | Clearance (CL) After Cycle 1 Treatment Administration of MEDI0639 | 1.06 Liter per day (L/d) | Standard Deviation 0.602 |
| MEDI0639 Cohort 3 | Clearance (CL) After Cycle 1 Treatment Administration of MEDI0639 | 0.895 Liter per day (L/d) | Standard Deviation 0.48 |
| MEDI0639 Cohort 4 | Clearance (CL) After Cycle 1 Treatment Administration of MEDI0639 | 0.619 Liter per day (L/d) | Standard Deviation 0.23 |
| MEDI0639 Cohort 5 | Clearance (CL) After Cycle 1 Treatment Administration of MEDI0639 | 0.360 Liter per day (L/d) | Standard Deviation 0.086 |
| MEDI0639 Cohort 6 | Clearance (CL) After Cycle 1 Treatment Administration of MEDI0639 | 0.504 Liter per day (L/d) | Standard Deviation 0.33 |
Secondary
Duration of Response (DR)
DR defined as time from start of first documented objective response \[confirmed Complete Response (CR) or confirmed Partial Response (PR)\] to first documented disease progression or death due to any cause, whichever occurs first. DR calculated as (months) = (Date of PD/death or censoring - Date of first disease response + 1)/ (365.25/12).
Time frame: From study entry through the end of the study. Maximum time frame across participants was 4 years.
Population: All participants who received at least one dose of MEDI0639. All participants with an objective response were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI0639 Cohort 3 | Duration of Response (DR) | 5.9 Months |
Secondary
Half-life (t1/2) After Cycle 1 Treatment Administration of MEDI0639
The pharmacokinetics (PK) parameter was estimated using the noncompartmental analysis methods, based on the individual serum concentration-time data. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI0639.
Time frame: Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1
Population: All the participants who received dose of MEDI0639 in Cycle 1 and for whom PK blood samples were collected and evaluated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI0639 | Half-life (t1/2) After Cycle 1 Treatment Administration of MEDI0639 | 1.50 Days | Standard Deviation 0.193 |
| MEDI0639 Cohort 2 | Half-life (t1/2) After Cycle 1 Treatment Administration of MEDI0639 | 2.53 Days | Standard Deviation 0.58 |
| MEDI0639 Cohort 3 | Half-life (t1/2) After Cycle 1 Treatment Administration of MEDI0639 | 5.09 Days | Standard Deviation 3.43 |
| MEDI0639 Cohort 4 | Half-life (t1/2) After Cycle 1 Treatment Administration of MEDI0639 | 6.42 Days | Standard Deviation 1.93 |
| MEDI0639 Cohort 5 | Half-life (t1/2) After Cycle 1 Treatment Administration of MEDI0639 | 9.74 Days | Standard Deviation 2.26 |
| MEDI0639 Cohort 6 | Half-life (t1/2) After Cycle 1 Treatment Administration of MEDI0639 | 8.25 Days | Standard Deviation 3.11 |
Secondary
Maximum Observed Concentration (Cmax) After Cycle 1 Treatment Administration of MEDI0639
The pharmacokinetics (PK) parameter was estimated using the noncompartmental analysis methods, based on the individual serum concentration-time data. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI0639.
Time frame: Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1
Population: All the participants who received dose of MEDI0639 in Cycle 1 and for whom PK blood samples were collected and evaluated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI0639 | Maximum Observed Concentration (Cmax) After Cycle 1 Treatment Administration of MEDI0639 | 3.19 microgram per milliliter (mcg/mL) | Standard Deviation 0.759 |
| MEDI0639 Cohort 2 | Maximum Observed Concentration (Cmax) After Cycle 1 Treatment Administration of MEDI0639 | 11.8 microgram per milliliter (mcg/mL) | Standard Deviation 2.45 |
| MEDI0639 Cohort 3 | Maximum Observed Concentration (Cmax) After Cycle 1 Treatment Administration of MEDI0639 | 18.3 microgram per milliliter (mcg/mL) | Standard Deviation 4.96 |
| MEDI0639 Cohort 4 | Maximum Observed Concentration (Cmax) After Cycle 1 Treatment Administration of MEDI0639 | 27.2 microgram per milliliter (mcg/mL) | Standard Deviation 7.32 |
| MEDI0639 Cohort 5 | Maximum Observed Concentration (Cmax) After Cycle 1 Treatment Administration of MEDI0639 | 60.5 microgram per milliliter (mcg/mL) | Standard Deviation 13.5 |
| MEDI0639 Cohort 6 | Maximum Observed Concentration (Cmax) After Cycle 1 Treatment Administration of MEDI0639 | 81.6 microgram per milliliter (mcg/mL) | Standard Deviation 47.3 |
Secondary
Number of Participants Positive With Antidrug Antibodies (ADA) for MEDI0639
Blood samples were measured for the presence of ADA for MEDI0639 using a validated bridging immunoassay. Only the number of participants positive for anti-MEDI-575 antibodies at any visit were presented.
Time frame: On Day 1 of Cycles 1, 2, 3, and every other cycle thereafter, end of treatment, 30 days, and 3 and 6 months after the last dose of MEDI0639. Maximum time frame across participants was 14 months.
Population: All participants who received any treatment with MEDI0639.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI0639 | Number of Participants Positive With Antidrug Antibodies (ADA) for MEDI0639 | 0 Participants |
| MEDI0639 Cohort 2 | Number of Participants Positive With Antidrug Antibodies (ADA) for MEDI0639 | 0 Participants |
| MEDI0639 Cohort 3 | Number of Participants Positive With Antidrug Antibodies (ADA) for MEDI0639 | 0 Participants |
| MEDI0639 Cohort 4 | Number of Participants Positive With Antidrug Antibodies (ADA) for MEDI0639 | 0 Participants |
| MEDI0639 Cohort 5 | Number of Participants Positive With Antidrug Antibodies (ADA) for MEDI0639 | 0 Participants |
| MEDI0639 Cohort 6 | Number of Participants Positive With Antidrug Antibodies (ADA) for MEDI0639 | 0 Participants |
Secondary
Overall Survival
Overall survival defined as the time from the first dose of MEDI0639 until death due to any cause. OS (months) = (Date of death or censoring - Date of the first dose of MEDI0639 + 1) / (365.25/12).
Time frame: From study entry through the end of the study. Maximum time frame across participants was 4 years.
Population: All participants who received at least one dose of MEDI0639.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI0639 | Overall Survival | 6.1 Months |
| MEDI0639 Cohort 2 | Overall Survival | NA Months |
| MEDI0639 Cohort 3 | Overall Survival | 28.9 Months |
| MEDI0639 Cohort 4 | Overall Survival | NA Months |
| MEDI0639 Cohort 5 | Overall Survival | 19.9 Months |
| MEDI0639 Cohort 6 | Overall Survival | 3.0 Months |
Secondary
Percentage of Participants With Best Overall Response
Percentage (%) of participants who were responders with BOR documented as confirmed CR, PR, stable disease (SD), progressive disease (PD) and non-evaluable (NE). CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 mm. PR: At least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: From study entry through the end of the study. Maximum time frame across participants was 4 years.
Population: All participants who received at least one dose of MEDI0639.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI0639 | Percentage of Participants With Best Overall Response | Progressive Disease (PD) | 33.3 Percentage of Participants |
| MEDI0639 | Percentage of Participants With Best Overall Response | Partial Response (PR) | 0 Percentage of Participants |
| MEDI0639 | Percentage of Participants With Best Overall Response | Complete Response (CR) | 0 Percentage of Participants |
| MEDI0639 | Percentage of Participants With Best Overall Response | Non-Evaluable (NE) | 0 Percentage of Participants |
| MEDI0639 | Percentage of Participants With Best Overall Response | Stable Disease (SD) | 66.7 Percentage of Participants |
| MEDI0639 Cohort 2 | Percentage of Participants With Best Overall Response | Partial Response (PR) | 0 Percentage of Participants |
| MEDI0639 Cohort 2 | Percentage of Participants With Best Overall Response | Progressive Disease (PD) | 66.7 Percentage of Participants |
| MEDI0639 Cohort 2 | Percentage of Participants With Best Overall Response | Complete Response (CR) | 0 Percentage of Participants |
| MEDI0639 Cohort 2 | Percentage of Participants With Best Overall Response | Non-Evaluable (NE) | 0 Percentage of Participants |
| MEDI0639 Cohort 2 | Percentage of Participants With Best Overall Response | Stable Disease (SD) | 33.3 Percentage of Participants |
| MEDI0639 Cohort 3 | Percentage of Participants With Best Overall Response | Partial Response (PR) | 33.3 Percentage of Participants |
| MEDI0639 Cohort 3 | Percentage of Participants With Best Overall Response | Progressive Disease (PD) | 33.3 Percentage of Participants |
| MEDI0639 Cohort 3 | Percentage of Participants With Best Overall Response | Non-Evaluable (NE) | 0 Percentage of Participants |
| MEDI0639 Cohort 3 | Percentage of Participants With Best Overall Response | Stable Disease (SD) | 33.3 Percentage of Participants |
| MEDI0639 Cohort 3 | Percentage of Participants With Best Overall Response | Complete Response (CR) | 0 Percentage of Participants |
| MEDI0639 Cohort 4 | Percentage of Participants With Best Overall Response | Stable Disease (SD) | 33.3 Percentage of Participants |
| MEDI0639 Cohort 4 | Percentage of Participants With Best Overall Response | Complete Response (CR) | 0 Percentage of Participants |
| MEDI0639 Cohort 4 | Percentage of Participants With Best Overall Response | Partial Response (PR) | 0 Percentage of Participants |
| MEDI0639 Cohort 4 | Percentage of Participants With Best Overall Response | Progressive Disease (PD) | 66.7 Percentage of Participants |
| MEDI0639 Cohort 4 | Percentage of Participants With Best Overall Response | Non-Evaluable (NE) | 0 Percentage of Participants |
| MEDI0639 Cohort 5 | Percentage of Participants With Best Overall Response | Progressive Disease (PD) | 20.0 Percentage of Participants |
| MEDI0639 Cohort 5 | Percentage of Participants With Best Overall Response | Complete Response (CR) | 0 Percentage of Participants |
| MEDI0639 Cohort 5 | Percentage of Participants With Best Overall Response | Non-Evaluable (NE) | 0 Percentage of Participants |
| MEDI0639 Cohort 5 | Percentage of Participants With Best Overall Response | Partial Response (PR) | 0 Percentage of Participants |
| MEDI0639 Cohort 5 | Percentage of Participants With Best Overall Response | Stable Disease (SD) | 80.0 Percentage of Participants |
| MEDI0639 Cohort 6 | Percentage of Participants With Best Overall Response | Complete Response (CR) | 0 Percentage of Participants |
| MEDI0639 Cohort 6 | Percentage of Participants With Best Overall Response | Progressive Disease (PD) | 60.0 Percentage of Participants |
| MEDI0639 Cohort 6 | Percentage of Participants With Best Overall Response | Partial Response (PR) | 0 Percentage of Participants |
| MEDI0639 Cohort 6 | Percentage of Participants With Best Overall Response | Non-Evaluable (NE) | 40.0 Percentage of Participants |
| MEDI0639 Cohort 6 | Percentage of Participants With Best Overall Response | Stable Disease (SD) | 0 Percentage of Participants |
Secondary
Percentage of Participants With Disease Control
Disease control rate (DCR) defined as the percentage of participants with a BOR of confirmed CR, confirmed PR or SD.
Time frame: From study entry through the end of the study. Maximum time frame across participants was 4 years.
Population: All participants who received at least one dose of MEDI0639.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI0639 | Percentage of Participants With Disease Control | 66.7 Percentage of Participants |
| MEDI0639 Cohort 2 | Percentage of Participants With Disease Control | 33.3 Percentage of Participants |
| MEDI0639 Cohort 3 | Percentage of Participants With Disease Control | 66.7 Percentage of Participants |
| MEDI0639 Cohort 4 | Percentage of Participants With Disease Control | 33.3 Percentage of Participants |
| MEDI0639 Cohort 5 | Percentage of Participants With Disease Control | 80.0 Percentage of Participants |
| MEDI0639 Cohort 6 | Percentage of Participants With Disease Control | 0 Percentage of Participants |
Secondary
Percentage of Participants With Objective Response
Objective response rate (ORR) defined as the percentage of participants with a BOR of confirmed CR or confirmed PR.
Time frame: From study entry through the end of the study. Maximum time frame across participants was 4 years.
Population: All participants who received at least one dose of MEDI0639. All participants with an objective response were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI0639 | Percentage of Participants With Objective Response | 0 Percentage of Participants |
| MEDI0639 Cohort 2 | Percentage of Participants With Objective Response | 0 Percentage of Participants |
| MEDI0639 Cohort 3 | Percentage of Participants With Objective Response | 33.3 Percentage of Participants |
| MEDI0639 Cohort 4 | Percentage of Participants With Objective Response | 0 Percentage of Participants |
| MEDI0639 Cohort 5 | Percentage of Participants With Objective Response | 0 Percentage of Participants |
| MEDI0639 Cohort 6 | Percentage of Participants With Objective Response | 0 Percentage of Participants |
Secondary
Progression-free Survival (PFS)
Progression-free survival (PFS) is defined as the time from the first dose of MEDI0639 until the first documentation of disease progression or death due to any cause, whichever occurs first. PFS (months) = (Date of PD/death or censoring - Date of the first dose of MEDI0639 + 1) / (365.25/12).
Time frame: From study entry through the end of the study. Maximum time frame across participants was 4 years.
Population: All participants who received at least one dose of MEDI0639.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI0639 | Progression-free Survival (PFS) | 5.1 Months |
| MEDI0639 Cohort 2 | Progression-free Survival (PFS) | 1.3 Months |
| MEDI0639 Cohort 3 | Progression-free Survival (PFS) | 7.1 Months |
| MEDI0639 Cohort 4 | Progression-free Survival (PFS) | 1.3 Months |
| MEDI0639 Cohort 5 | Progression-free Survival (PFS) | 4.8 Months |
| MEDI0639 Cohort 6 | Progression-free Survival (PFS) | 0.9 Months |
Secondary
Time to Response
Time to response (TTR) defined as the time from the first dose of MEDI0639 until the first documentation of a subsequently confirmed objective response. Only participants who have achieved objective response (confirmed CR or confirmed PR) was evaluated for TTR. TTR (months) = (Date of first disease response - Date of the first dose of MEDI0639 + 1) / (365.25/12).
Time frame: From study entry through the end of the study. Maximum time frame across participants was 4 years.
Population: All participants who received at least one dose of MEDI0639. All participants with an objective response were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI0639 Cohort 3 | Time to Response | 1.3 Months |