A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI0639 in Advanced Solid Tumors
Sponsor
MedImmune LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT01577745
Collaborator
(none)
58
11
6
44
5.3
0.1
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
58 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1, Multicenter, Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI0639 in Adult Subjects With Advanced Solid Tumors
Study Start Date
:
Apr 1, 2012
Actual Primary Completion Date
:
Dec 1, 2015
Actual Study Completion Date
:
Dec 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MEDI0639 Cohort 1 Participants received MEDI0639 dose level 1 as a 60-minute intravenous (IV) infusion on Day 1 of each 21-day cycle. |
Biological: MEDI0639
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.
|
| Experimental: MEDI0639 Cohort 2 Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
Biological: MEDI0639
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.
|
| Experimental: MEDI0639 Cohort 3 Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
Biological: MEDI0639
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.
|
| Experimental: MEDI0639 Cohort 4 Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
Biological: MEDI0639
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.
|
| Experimental: MEDI0639 Cohort 5 Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
Biological: MEDI0639
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.
|
| Experimental: MEDI0639 Cohort 6 Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21 day cycle. |
Biological: MEDI0639
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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- 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.
- 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).
- 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).
- 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).
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 99 Years
Sexes Eligible for Study:
All
Accepts 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Los Angeles | California | United States | 90404 |
| 2 | Research Site | New Haven | Connecticut | United States | 06513 |
| 3 | Research Site | Boston | Massachusetts | United States | |
| 4 | Research Site | Ann Arbor | Michigan | United States | 48103 |
| 5 | Research Site | Minneapolis | Minnesota | United States | |
| 6 | Research Site | New York | New York | United States | 10002 |
| 7 | Research Site | Cincinnati | Ohio | United States | 45201 |
| 8 | Research Site | Cleveland | Ohio | United States | 44105 |
| 9 | Research Site | Houston | Texas | United States | 77030 |
| 10 | Research Site | Seattle | Washington | United States | 98112 |
| 11 | Research Site | Tacoma | Washington | United States | 98405 |
Sponsors and Collaborators
- MedImmune LLC
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01577745
Other Study ID Numbers:
- CD-ON-MEDI0639-1078
First Posted:
Apr 16, 2012
Last Update Posted:
May 2, 2017
Last Verified:
Mar 1, 2017
Study Results
Participant Flow
| Recruitment Details | A total of 58 participants were screened at 7 sites in the United States of America (USA). |
|---|---|
| Pre-assignment Detail | A total of 58 participants were screened for this study, of which 25 participants were enrolled and received study treatment. |
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute intravenous (IV) infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21 day cycle. |
| Period Title: Overall Study | ||||||
| STARTED | 3 | 3 | 3 | 6 | 5 | 5 |
| COMPLETED | 0 | 0 | 1 | 0 | 0 | 1 |
| NOT COMPLETED | 3 | 3 | 2 | 6 | 5 | 4 |
Baseline Characteristics
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21 day cycle. | Total of all reporting groups |
| Overall Participants | 3 | 3 | 3 | 6 | 5 | 5 | 25 |
| Age (Years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [Years] |
55.7
(14.0)
|
57.3
(22.5)
|
67.7
(13.7)
|
62.2
(9.3)
|
62.2
(5.2)
|
62.6
(10.8)
|
61.6
(11.3)
|
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
0
0%
|
3
100%
|
1
33.3%
|
3
50%
|
3
60%
|
3
60%
|
13
52%
|
| Male |
3
100%
|
0
0%
|
2
66.7%
|
3
50%
|
2
40%
|
2
40%
|
12
48%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||
| Hispanic or Latino |
1
33.3%
|
1
33.3%
|
0
0%
|
0
0%
|
1
20%
|
0
0%
|
3
12%
|
| Not Hispanic or Latino |
2
66.7%
|
2
66.7%
|
3
100%
|
6
100%
|
4
80%
|
5
100%
|
22
88%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
4%
|
| White |
3
100%
|
2
66.7%
|
3
100%
|
6
100%
|
5
100%
|
5
100%
|
24
96%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Maximum Tolerated Dose (MTD) of MEDI0639 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | MEDI0639 |
|---|---|
| Arm/Group Description | Participants received MEDI0639, in dose escalation phase starting from dose level 1 to 6 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
| Measure Participants | 25 |
| Number [milligram (mg)] |
NA
|
| Title | Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of MEDI0639. |
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21 day cycle. |
| Measure Participants | 3 | 3 | 3 | 6 | 5 | 5 |
| Number [participants] |
3
100%
|
3
100%
|
3
100%
|
6
100%
|
5
100%
|
5
100%
|
| Title | Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of MEDI0639. |
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
| Measure Participants | 3 | 3 | 3 | 6 | 5 | 5 |
| Number [Participants] |
2
66.7%
|
1
33.3%
|
2
66.7%
|
2
33.3%
|
4
80%
|
3
60%
|
| Title | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of MEDI0639. |
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
| Measure Participants | 3 | 3 | 3 | 6 | 5 | 5 |
| Anaemia |
2
66.7%
|
0
0%
|
0
0%
|
3
50%
|
3
60%
|
1
20%
|
| Leukocytosis |
1
33.3%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Leukopenia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
0
0%
|
| Lymphopenia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
40%
|
| Neutropenia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
0
0%
|
| Thrombocytopenia |
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
1
20%
|
0
0%
|
| White blood cell count decreased |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Alanine aminotransferase increased |
0
0%
|
1
33.3%
|
2
66.7%
|
0
0%
|
0
0%
|
1
20%
|
| Aspartate aminotransferase increased |
1
33.3%
|
2
66.7%
|
2
66.7%
|
1
16.7%
|
0
0%
|
2
40%
|
| Blood alkaline phosphatase increased |
1
33.3%
|
0
0%
|
2
66.7%
|
2
33.3%
|
0
0%
|
0
0%
|
| Blood bilirubin increased |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Blood cholesterol increased |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
| Blood creatinine increased |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Blood lactate dehydrogenase increased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
| Blood triglycerides increased |
1
33.3%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
| Brain natriuretic peptide increased |
1
33.3%
|
1
33.3%
|
0
0%
|
2
33.3%
|
2
40%
|
0
0%
|
| Gamma-glutamyltransferase increased |
3
100%
|
1
33.3%
|
2
66.7%
|
2
33.3%
|
0
0%
|
0
0%
|
| N-terminal prohormone BNP increased |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
| Troponin I increased |
2
66.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Troponin increased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
| Hepatobiliary disorders |
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
0
0%
|
| Hyperbilirubinaemia |
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Metabolism and nutrition disorders |
2
66.7%
|
3
100%
|
3
100%
|
3
50%
|
3
60%
|
2
40%
|
| Dyslipidaemia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
0
0%
|
| Hypercalcaemia |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
1
20%
|
0
0%
|
| Hypercholesterolaemia |
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Hyperglycaemia |
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
1
20%
|
0
0%
|
| Hyperkalaemia |
1
33.3%
|
0
0%
|
1
33.3%
|
0
0%
|
1
20%
|
0
0%
|
| Hypernatraemia |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
| Hyperphosphataemia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
0
0%
|
| Hypertriglyceridaemia |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
1
20%
|
0
0%
|
| Hyperuricaemia |
0
0%
|
1
33.3%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
| Hypoalbuminaemia |
1
33.3%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
| Hypocalcaemia |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
| Hypoglycaemia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
| Hypokalaemia |
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Hypomagnesaemia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
0
0%
|
| Hyponatraemia |
0
0%
|
1
33.3%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Hypophosphataemia |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| WBC urine positive |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
| Proteinuria |
1
33.3%
|
1
33.3%
|
0
0%
|
0
0%
|
1
20%
|
1
20%
|
| Title | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of MEDI0639. |
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
| Measure Participants | 3 | 3 | 3 | 6 | 5 | 5 |
| Electrocardiogram QT prolonged |
1
33.3%
|
1
33.3%
|
0
0%
|
2
33.3%
|
0
0%
|
0
0%
|
| Weight decreased |
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Electrocardiogram t wave amplitude decreased |
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Hypotension |
0
0%
|
1
33.3%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
| Pyrexia |
0
0%
|
2
66.7%
|
0
0%
|
2
33.3%
|
2
40%
|
0
0%
|
| Atrial fibrillation |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
| Hypertension |
0
0%
|
0
0%
|
1
33.3%
|
2
33.3%
|
1
20%
|
1
20%
|
| Atrioventricular block first degree |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Electrocardiogram ST-T change |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Sinus tachycardia |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of MEDI0639. |
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
| Measure Participants | 3 | 3 | 3 | 6 | 5 | 5 |
| ECG QT prolonged |
1
33.3%
|
1
33.3%
|
0
0%
|
2
33.3%
|
0
0%
|
0
0%
|
| Electrocardiogram t wave amplitude decreased |
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Atrial fibrillation |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
| Atrioventricular block first degree |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Electrocardiogram ST-T change |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Echocardiogram Evaluations |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of MEDI0639. |
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
| Measure Participants | 3 | 3 | 3 | 6 | 5 | 5 |
| Number [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) After Cycle 1 Treatment Administration of MEDI0639 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All the participants who received dose of MEDI0639 in Cycle 1 and for whom Pharmacokinetic (PK) blood samples were collected and evaluated. |
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
| Measure Participants | 3 | 3 | 3 | 6 | 5 | 5 |
| Mean (Standard Deviation) [microgram*day per milliliter (mcg*d/mL)] |
7.41
(1.04)
|
41.1
(34.0)
|
89.9
(64.9)
|
179
(59.9)
|
434
(91.9)
|
512
(250)
|
| Title | Maximum Observed Concentration (Cmax) After Cycle 1 Treatment Administration of MEDI0639 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All the participants who received dose of MEDI0639 in Cycle 1 and for whom PK blood samples were collected and evaluated. |
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
| Measure Participants | 3 | 3 | 3 | 6 | 5 | 5 |
| Mean (Standard Deviation) [microgram per milliliter (mcg/mL)] |
3.19
(0.759)
|
11.8
(2.45)
|
18.3
(4.96)
|
27.2
(7.32)
|
60.5
(13.5)
|
81.6
(47.3)
|
| Title | Clearance (CL) After Cycle 1 Treatment Administration of MEDI0639 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All the participants who received dose of MEDI0639 in Cycle 1 and for whom PK blood samples were collected and evaluated. |
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
| Measure Participants | 3 | 3 | 3 | 6 | 5 | 5 |
| Mean (Standard Deviation) [Liter per day (L/d)] |
1.37
(0.182)
|
1.06
(0.602)
|
0.895
(0.480)
|
0.619
(0.230)
|
0.360
(0.0860)
|
0.504
(0.330)
|
| Title | Half-life (t1/2) After Cycle 1 Treatment Administration of MEDI0639 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All the participants who received dose of MEDI0639 in Cycle 1 and for whom PK blood samples were collected and evaluated. |
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
| Measure Participants | 3 | 3 | 3 | 6 | 5 | 5 |
| Mean (Standard Deviation) [Days] |
1.50
(0.193)
|
2.53
(0.580)
|
5.09
(3.43)
|
6.42
(1.93)
|
9.74
(2.26)
|
8.25
(3.11)
|
| Title | Number of Participants Positive With Antidrug Antibodies (ADA) for MEDI0639 |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received any treatment with MEDI0639. |
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
| Measure Participants | 3 | 3 | 3 | 6 | 5 | 5 |
| Number [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Percentage of Participants With Best Overall Response |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of MEDI0639. |
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
| Measure Participants | 3 | 3 | 3 | 6 | 5 | 5 |
| Complete Response (CR) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Partial Response (PR) |
0
0%
|
0
0%
|
33.3
1110%
|
0
0%
|
0
0%
|
0
0%
|
| Stable Disease (SD) |
66.7
2223.3%
|
33.3
1110%
|
33.3
1110%
|
33.3
555%
|
80.0
1600%
|
0
0%
|
| Progressive Disease (PD) |
33.3
1110%
|
66.7
2223.3%
|
33.3
1110%
|
66.7
1111.7%
|
20.0
400%
|
60.0
1200%
|
| Non-Evaluable (NE) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
40.0
800%
|
| Title | Percentage of Participants With Objective Response |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of MEDI0639. All participants with an objective response were included. |
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MMEDI0639 Cohort 5 | MMEDI0639 Cohort 6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle.. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
| Measure Participants | 3 | 3 | 3 | 6 | 5 | 5 |
| Number (95% Confidence Interval) [Percentage of Participants] |
0
0%
|
0
0%
|
33.3
1110%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Percentage of Participants With Disease Control |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of MEDI0639. |
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
| Measure Participants | 3 | 3 | 3 | 6 | 5 | 5 |
| Number (95% Confidence Interval) [Percentage of Participants] |
66.7
2223.3%
|
33.3
1110%
|
66.7
2223.3%
|
33.3
555%
|
80.0
1600%
|
0
0%
|
| Title | Time to Response |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of MEDI0639. All participants with an objective response were included. |
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
| Measure Participants | 0 | 0 | 1 | 0 | 0 | 0 |
| Median (95% Confidence Interval) [Months] |
1.3
|
| Title | Duration of Response (DR) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of MEDI0639. All participants with an objective response were included. |
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
| Measure Participants | 0 | 0 | 1 | 0 | 0 | 0 |
| Median (95% Confidence Interval) [Months] |
5.9
|
| Title | Progression-free Survival (PFS) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of MEDI0639. |
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
| Measure Participants | 3 | 3 | 3 | 6 | 5 | 5 |
| Median (95% Confidence Interval) [Months] |
5.1
|
1.3
|
7.1
|
1.3
|
4.8
|
0.9
|
| Title | Overall Survival |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of MEDI0639. |
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21-day cycle. |
| Measure Participants | 3 | 3 | 3 | 6 | 5 | 5 |
| Median (95% Confidence Interval) [Months] |
6.1
|
NA
|
28.9
|
NA
|
19.9
|
3.0
|
Adverse Events
| Time Frame | AEs collected from first dose of MEDI0639 to 90 days post dose of MEDI0639, max time frame across participants was 11 months. SAEs collected from the first dose of MEDI0639 to end of participation in study; max time frame across participants was 4 yrs. | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||
| Arm/Group Title | MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 | ||||||
| Arm/Group Description | Participants received MEDI0639 dose level 1 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle. | Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21 day cycle. | ||||||
All Cause Mortality |
||||||||||||
| MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||
Serious Adverse Events |
||||||||||||
| MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/3 (66.7%) | 1/3 (33.3%) | 2/3 (66.7%) | 2/6 (33.3%) | 4/5 (80%) | 3/5 (60%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Anaemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 1/5 (20%) | 1 |
| Thrombocytopenia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Cardiac disorders | ||||||||||||
| Acute coronary syndrome | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
| Acute myocardial infarction | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Atrial fibrillation | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Dilatation ventricular | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Ventricular hypokinesia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Eye disorders | ||||||||||||
| Diplopia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||
| Constipation | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Nausea | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Vomiting | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| General disorders | ||||||||||||
| Chest discomfort | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Fatigue | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Non-cardiac chest pain | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Infections and infestations | ||||||||||||
| Gastroenteritis pseudomonas | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Sepsis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||
| Post procedural complication | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Investigations | ||||||||||||
| Troponin increased | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
| Metabolism and nutrition disorders | ||||||||||||
| Decreased appetite | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Hypercalcaemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Hypophosphataemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Back pain | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
| Cholangiocarcinoma | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Malignant neoplasm progression | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Metastases to central nervous system | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Nervous system disorders | ||||||||||||
| Cerebral haemorrhage | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||
| Acute kidney injury | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Acute respiratory failure | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
| Dyspnoea | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Pleuritic pain | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Respiratory failure | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/5 (20%) | 2 |
Other (Not Including Serious) Adverse Events |
||||||||||||
| MEDI0639 Cohort 1 | MEDI0639 Cohort 2 | MEDI0639 Cohort 3 | MEDI0639 Cohort 4 | MEDI0639 Cohort 5 | MEDI0639 Cohort 6 | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) | 6/6 (100%) | 5/5 (100%) | 4/5 (80%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Anaemia | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/6 (50%) | 3 | 3/5 (60%) | 4 | 0/5 (0%) | 0 |
| Leukocytosis | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Lymphopenia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 2/5 (40%) | 2 |
| Endocrine disorders | ||||||||||||
| Hypothyroidism | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||
| Abdominal distension | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Abdominal pain | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 3 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Abdominal pain lower | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Constipation | 2/3 (66.7%) | 2 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Diarrhoea | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 5 | 0/6 (0%) | 0 | 3/5 (60%) | 4 | 1/5 (20%) | 1 |
| Gastrooesophageal reflux disease | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Gingival bleeding | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/5 (40%) | 2 | 0/5 (0%) | 0 |
| Nausea | 2/3 (66.7%) | 3 | 3/3 (100%) | 4 | 1/3 (33.3%) | 1 | 2/6 (33.3%) | 2 | 3/5 (60%) | 4 | 3/5 (60%) | 3 |
| Toothache | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Vomiting | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 3 | 2/5 (40%) | 2 |
| General disorders | ||||||||||||
| Fatigue | 2/3 (66.7%) | 2 | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 3 | 2/6 (33.3%) | 2 | 3/5 (60%) | 3 | 0/5 (0%) | 0 |
| Influenza like illness | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Oedema peripheral | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 2/5 (40%) | 2 |
| Pyrexia | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 2/5 (40%) | 3 | 0/5 (0%) | 0 |
| Infections and infestations | ||||||||||||
| Pneumonia | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Urinary tract infection | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Investigations | ||||||||||||
| Alanine aminotransferase increased | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 3 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
| Aspartate aminotransferase increased | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 2 | 2/3 (66.7%) | 2 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 2/5 (40%) | 3 |
| Blood alkaline phosphatase increased | 1/3 (33.3%) | 3 | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 | 2/6 (33.3%) | 2 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Blood triglycerides increased | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Brain natriuretic peptide increased | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 2/5 (40%) | 2 | 0/5 (0%) | 0 |
| Electrocardiogram qt prolonged | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Gamma-glutamyltransferase increased | 3/3 (100%) | 3 | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 3 | 2/6 (33.3%) | 3 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Troponin i increased | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||
| Decreased appetite | 1/3 (33.3%) | 4 | 2/3 (66.7%) | 3 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 2/5 (40%) | 3 | 1/5 (20%) | 1 |
| Dehydration | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Hypercalcaemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Hyperglycaemia | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Hyperkalaemia | 1/3 (33.3%) | 3 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Hypertriglyceridaemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Hyperuricaemia | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Hypoalbuminaemia | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/5 (20%) | 2 |
| Hyponatraemia | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Musculoskeletal chest pain | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Musculoskeletal pain | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Myalgia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Nervous system disorders | ||||||||||||
| Dizziness | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 1/5 (20%) | 1 |
| Dysgeusia | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Headache | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 | 4/6 (66.7%) | 4 | 2/5 (40%) | 4 | 0/5 (0%) | 0 |
| Psychiatric disorders | ||||||||||||
| Anxiety | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
| Insomnia | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||
| Nocturia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
| Proteinuria | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 1/5 (20%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Cough | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
| Dyspnoea | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 2/5 (40%) | 2 | 2/5 (40%) | 2 |
| Vascular disorders | ||||||||||||
| Hypertension | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 3 | 2/6 (33.3%) | 2 | 1/5 (20%) | 1 | 1/5 (20%) | 1 |
| Hypotension | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 |
Limitations/Caveats
OMs relationship modulation of DLL4-Notch signaling pathway in tumor and clinical response analysis was not conducted due to low number of evaluable tumor samples and low response rate. Study was terminated early due to lack of clinical activity.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
Results Point of Contact
| Name/Title | Mohammed Dar |
|---|---|
| Organization | MedImmune, LLC |
| Phone | 301-398-1008 |
| information.center@astrazeneca.com |
Responsible Party:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01577745
Other Study ID Numbers:
- CD-ON-MEDI0639-1078
First Posted:
Apr 16, 2012
Last Update Posted:
May 2, 2017
Last Verified:
Mar 1, 2017