A Study to Evaluate the Safety and Antitumor Activity in Subjects With Advanced Solid Tumors
Sponsor
MedImmune LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT01248949
Collaborator
(none)
162
10
5
60
16.2
0.3
Study Details
Study Description
Brief Summary
To determine the maximum tolerated dose or optimal biological dose, and the safety profile of MEDI3617 when given as a single-agent or in combination with other chemotherapeutic agents in subjects with advanced solid malignancies resistant to standard therapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
162 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1/1b, Open-Label, Dose-Escalation and Expansion Study to Evaluate the Safety and Antitumor Activity of MEDI3617 as a Single-Agent or in Combination Therapy in Adult Subjects With Advanced Solid Tumors
Study Start Date
:
Oct 1, 2010
Actual Primary Completion Date
:
Jul 1, 2015
Actual Study Completion Date
:
Oct 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MEDI3617 SINGLE AGENT TOTAL Participants will receive MEDI3617 via intravenous (IV) infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. |
Drug: MEDI3617
Participants will receive MEDI3617 via IV infusion in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons.
|
| Experimental: MEDI3617 + BEVACIZUMAB Q3W ESCALATION Participants will receive MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. |
Drug: MEDI3617
Participants will receive MEDI3617 via IV infusion in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons.
Drug: Bevacizumab
Participants will receive bevacizumab via IV infusion in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons.
|
| Experimental: MEDI3617 + BEVACIZUMAB Q2W TOTAL Participants will receive MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. |
Drug: MEDI3617
Participants will receive MEDI3617 via IV infusion in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons.
Drug: Bevacizumab
Participants will receive bevacizumab via IV infusion in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons.
|
| Experimental: MEDI3617 + PACLITAXEL TOTAL Participants will receive MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. |
Drug: MEDI3617
Participants will receive MEDI3617 via IV infusion in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons.
Drug: Paclitaxel
Participants will receive paclitaxel via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons.
|
| Experimental: MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL Participants will receive MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
Drug: MEDI3617
Participants will receive MEDI3617 via IV infusion in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons.
Drug: Paclitaxel
Participants will receive paclitaxel via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons.
Drug: Carboplatin
Participants will receive carboplatin via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Dose Limiting Toxicities (DLTs) [From the time of first administration of MEDI3617 single agent or MEDI3617 combination therapy through the first 21-day or 28-day cycle (Cycle 1)]
DLT was defined as any treatment-related, grade 3 or higher toxicity (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0); occurring during the first 21 or 28 days after the initial administration of MEDI3617.
- Maximum Tolerated Dose (MTD) [From the time of first administration of MEDI3617 single agent or MEDI3617 combination therapy through the first 21-day or 28-day cycle (Cycle 1)]
The dose-escalation phase used a 3 + 3 design. If greater than or equal to 2 (≥ 2) participants in a dose cohort experienced a DLT during the DLT period, the MTD was exceeded and no further participants were enrolled into that dose cohort. If this occurred, the preceding dose cohort was evaluated for the MTD and a total of 6 participants were treated at the preceding dose. If less than or equal to 1 (≤ 1) of 6 participants experienced a DLT at the preceding dose, then this dose level was the MTD. DLTs were defined as any treatment-related, grade 3 or higher toxicity (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0); occurring during the first 21 or 28 days after the initial administration of MEDI3617.
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) [From start of study drug administration up to 90 days after the last dose of MEDI3617]
An adverse event (AE) was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events occurring after administration of investigational product.
- Number of Participants With Laboratory Abnormalities Recorded as Adverse Events (AEs) [From start of study drug administration up to 90 days after the last dose of MEDI3617]
Laboratory evaluations were performed, including hematology and serum chemistry. An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to laboratory abnormalities were recorded and reported.
- Number of Participants With Vital Sign Abnormalities Recorded as Adverse Events (AEs) [From start of study drug administration up to 90 days after the last dose of MEDI3617]
Vital signs included parameters such as heart rate, blood pressure, temperature, weight and respiratory rate. An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to vital signs abnormalities were recorded and reported.
- Number of Participants With Echocardiogram Abnormalities Recorded as Adverse Events (AEs) [From start of study drug administration up to 90 days after the last dose of MEDI3617]
An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to echocardiogram abnormalities were recorded and reported. The only AE reported was ejection fraction decreased in the MEDI3617 + Paclitaxel total group.
- Number of Participants With Electrocardiogram Abnormalities Recorded as Adverse Events (AEs) [From start of study drug administration up to 90 days after the last dose of MEDI3617]
An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to electrocardiogram abnormalities were recorded and reported. The only AE reported was electrocardiogram QT prolonged in the MEDI3617 + Bevacizumab Q2W total group.
- Number of Participants With a Decline in Karnofsky Performance Status (KPS) of ≥ 20 Points at Worst Record On-study Compared With Baseline [From start of study drug administration up to 30 days after the last dose of MEDI3617]
KPS scale: 100 is no evidence of disease; 90 is able to carry on normal activity, minor symptoms of disease; 80 is normal activity with effort, some symptoms of disease; 70 is cares for self; unable to do active work; 60 is requires occasional assistance, but is able to care for most of his needs; 50 is requires considerable assistance with frequent medical care; 40 is disabled, requires special care; 30 is severely disabled, hospitalization is indicated although death is not imminent; 20 is very sick, hospitalization necessary, active support treatment necessary; 10 is moribund, fatal processes progressing rapidly, 0 is dead.
Secondary Outcome Measures
- Maximum Observed Serum Concentration (Cmax) of MEDI3617 [Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose]
Cmax is the maximum observed serum concentration of MEDI3617. Here, "n" is number of participants analyzed for this endpoint at a specific dose.
- Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI3617 [Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose]
AUC0-last is the Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration of MEDI3617. Here, "n" is number of participants analyzed for this endpoint at a specific dose.
- Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of MEDI3617 [Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose]
The AUC0-inf is the Area Under the Concentration-Time Curve From Time Zero to infinity of MEDI3617. Here, "n" is number of participants analyzed for this endpoint at a specific dose.
- Systemic Clearance (CL) of MEDI3617 [Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose]
Systemic clearance describes the removal of drug from a volume of serum in a given unit of time (drug loss from the body). It is measured as milliliter per day (mL/day). Here, "n" is number of participants analyzed for this endpoint at a specific dose.
- Terminal Elimination Half Life (t1/2) of MEDI3617 [Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose]
The t1/2 is the time in days required for the concentration of the drug to reach half of its original value. Here, "n" is number of participants analyzed for this endpoint at a specific dose.
- Number of Participants With Positive Anti-Drug Antibody (ADA) [Presence of ADA to MEDI3617 were assessed prior to infusion with MEDI3617 on Day 1 of each dosing cycle, as well as the end of treatment, and 30 days, 3 months, and 6 months post last dose of MEDI3617]
The immunogenic potential of MEDI3617 was assessed by summarizing the number and percentage of participants who develop detectable ADA. Immunogenicity assessment included determination of anti-drug (MEDI3617) antibodies in serum samples. Samples were measured for the presence of ADA using validated immunoassays.
- Objective Response Rate (ORR) [Time from the first dose of investigational product until end of study]
Objective response rate defined as the number of participants with confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to less than (<) 10 millimeter (the sum may not be "0" if there are target nodes). PR was defined as at least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
- Time to Response (TTR) [Time from the first dose of investigational product until end of study]
Time to response (TTR) is defined as the time from the study entry to the first documentation of confirmed CR or confirmed PR. CR was defined as disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to less than (<) 10 millimeter (the sum may not be "0" if there are target nodes). PR was defined as at least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Analysis was based on responses confirmed at a repeat assessment made at least 4 weeks after the initial response, with the TTR taken as the first time the response was observed, not the confirmation assessment. TTR was evaluated using the Kaplan-Meier method.
- Duration of Response (DOR) [Time from the first dose of investigational product until end of study]
Duration of response is defined as the duration from the first documentation of objective disease response (ie, confirmed CR or confirmed PR) to the first documented disease progression. The duration of response was censored on the date of last tumor assessment documenting absence of disease progression for participants who have no documented progression prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. Duration of response was evaluated for the subgroup of participants with an objective response using the Kaplan-Meier method.
- Time to Progression (TTP) [Time from the first dose of investigational product until end of study]
Time to progression (TTP) is defined as time from the start of treatment with MEDI3617 until the documentation of disease progression. The TTP was censored on the date of last tumor assessment documenting absence of tumor progression for participants who have no documented progression prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. Participants having no tumor assessments after the start of treatment with MEDI3617 had TTP censored on the first date of treatment with MEDI3617. TTP was evaluated using the Kaplan-Meier method.
- Progression-Free Survival (PFS) [Time from the first dose of investigational product until end of study]
PFS was measured from the start of treatment with MEDI3617 until the documentation of disease progression or death due to any cause, whichever occurred first. PFS was censored on the date of last tumor assessment documenting absence of tumor progression for participants who have no documented progression and were still alive prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. Participants having no tumor assessments after the start of treatment with MEDI3617 had PFS censored on the first date of treatment with MEDI3617. PFS was evaluated using the Kaplan-Meier method.
- Overall Survival (OS) [Time from the first dose of investigational product until death due to any cause]
Overall survival is defined as the time from the start of treatment with MEDI3617 until death. For the participants who were alive at the end of study or lost to follow-up, overall survival was censored on the last date when participants were known to be alive. Overall survival was evaluated using the Kaplan-Meier method.
- Circulating Levels of Angiopoietin 2 (Ang2) [Prior to infusion on Cycle 4 and Cycle 5]
Profile of Ang2 post MEDI3617 administration in relation to time course of antibody concentrations.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 99 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Patients with confirmed diagnosis of advanced solid tumors (dose-escalation phase) or another solid tumor type based on antitumoral activity (dose-expansion phase) that are not responsive to standard therapy or for which no standard therapy exists
-
Patients must be 18 years of age or older
-
Karnofsky Performance Status ≥ 70
-
Toxicities from previous cancer therapies must have recovered to CTCAE Grade = or < 2
-
Adequate organ and marrow function
-
Using adequate contraceptive measures, be surgically sterile or post-menopausal
Exclusion Criteria:
-
Concurrently enrolled in another clinical study, except for non-interventiona observational studies, or if in a follow up period from a previous study
-
Receipt of any investigational anticancer therapy within 30 days prior to the first dose of MEDI3617, or in the case of monoclonal antibodies (eg, bevacizumab), 42 days prior to the first dose of MEDI3617
-
Current or previous treatment with angiopoietin inhibitors, or inhibitors of Tie1 or Tie2 including, but not limited to, AMG386, CVX-060, XL880, and XL820
-
Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment
-
Use of immunosuppressive medication or systemic steroids within 7 days prior to first dose of MEDI3617
-
Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results
-
Known bleeding diathesis
-
Pulmonary hemorrhage or gross hemoptysis within 6 months prior to enrollment
-
Therapeutic or palliative radiation therapy within 2 weeks prior to enrollment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Los Angeles | California | United States | |
| 2 | Research Site | Stanford | California | United States | |
| 3 | Research Site | Lafayette | Indiana | United States | |
| 4 | Research Site | Baltimore | Maryland | United States | |
| 5 | Research Site | Boston | Massachusetts | United States | |
| 6 | Research Site | Detroit | Michigan | United States | |
| 7 | Research Site | Buffalo | New York | United States | |
| 8 | Research Site | New York | New York | United States | |
| 9 | Research Site | Philadelphia | Pennsylvania | United States | |
| 10 | Research Site | Nashville | Tennessee | United States |
Sponsors and Collaborators
- MedImmune LLC
Investigators
- Study Director: MedImmune, LLC, MedImmune LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01248949
Other Study ID Numbers:
- CD-ON-MEDI3617-1043
First Posted:
Nov 25, 2010
Last Update Posted:
Mar 29, 2017
Last Verified:
Feb 1, 2017
Keywords provided by MedImmune LLC
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | A total of 162 participants were screened, of which 46 did not meet eligibility criteria and were considered as screen failures; the remaining 116 participants entered into the study and treated with MEDI3617. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/ PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Period Title: Overall Study | |||||
| STARTED | 42 | 16 | 38 | 13 | 7 |
| COMPLETED | 9 | 3 | 1 | 3 | 3 |
| NOT COMPLETED | 33 | 13 | 37 | 10 | 4 |
Baseline Characteristics
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. | Total of all reporting groups |
| Overall Participants | 42 | 16 | 38 | 13 | 7 | 116 |
| Age (Years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [Years] |
61.4
(12.4)
|
57.4
(11.9)
|
57.7
(11.2)
|
60.4
(12.7)
|
56.7
(12.3)
|
59.2
(11.9)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
27
64.3%
|
7
43.8%
|
18
47.4%
|
8
61.5%
|
5
71.4%
|
65
56%
|
| Male |
15
35.7%
|
9
56.3%
|
20
52.6%
|
5
38.5%
|
2
28.6%
|
51
44%
|
Outcome Measures
| Title | Number of Participants With Dose Limiting Toxicities (DLTs) |
|---|---|
| Description | DLT was defined as any treatment-related, grade 3 or higher toxicity (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0); occurring during the first 21 or 28 days after the initial administration of MEDI3617. |
| Time Frame | From the time of first administration of MEDI3617 single agent or MEDI3617 combination therapy through the first 21-day or 28-day cycle (Cycle 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| DLT Evaluable population included all participants enrolled in dose-escalation, who received at least 1 full assigned dose of single-agent MEDI3617 or full assigned doses of MEDI3617 and standard therapeutic agents on Cycle 1 and completed safety follow-up or experienced a DLT at any point during the 21-day or 28-day DLT evaluation period. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 23 | 15 | 22 | 11 | 6 |
| Number [Participants] |
1
2.4%
|
1
6.3%
|
2
5.3%
|
1
7.7%
|
1
14.3%
|
| Title | Maximum Tolerated Dose (MTD) |
|---|---|
| Description | The dose-escalation phase used a 3 + 3 design. If greater than or equal to 2 (≥ 2) participants in a dose cohort experienced a DLT during the DLT period, the MTD was exceeded and no further participants were enrolled into that dose cohort. If this occurred, the preceding dose cohort was evaluated for the MTD and a total of 6 participants were treated at the preceding dose. If less than or equal to 1 (≤ 1) of 6 participants experienced a DLT at the preceding dose, then this dose level was the MTD. DLTs were defined as any treatment-related, grade 3 or higher toxicity (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0); occurring during the first 21 or 28 days after the initial administration of MEDI3617. |
| Time Frame | From the time of first administration of MEDI3617 single agent or MEDI3617 combination therapy through the first 21-day or 28-day cycle (Cycle 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| DLT Evaluable population included all participants enrolled in dose-escalation, who received at least 1 full assigned dose of single-agent MEDI3617 or full assigned doses of MEDI3617 and standard therapeutic agents on Cycle 1 and completed safety follow-up or experienced a DLT at any point during the 21-day or 28-day DLT evaluation period. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 23 | 15 | 22 | 11 | 6 |
| Number [milligram (mg)] |
NA
|
NA
|
NA
|
NA
|
NA
|
| Title | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) |
|---|---|
| Description | An adverse event (AE) was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events occurring after administration of investigational product. |
| Time Frame | From start of study drug administration up to 90 days after the last dose of MEDI3617 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants who received treatment with MEDI3617. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 42 | 16 | 38 | 13 | 7 |
| TEAEs |
42
100%
|
16
100%
|
38
100%
|
13
100%
|
7
100%
|
| TESAEs |
18
42.9%
|
4
25%
|
18
47.4%
|
7
53.8%
|
4
57.1%
|
| Title | Number of Participants With Laboratory Abnormalities Recorded as Adverse Events (AEs) |
|---|---|
| Description | Laboratory evaluations were performed, including hematology and serum chemistry. An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to laboratory abnormalities were recorded and reported. |
| Time Frame | From start of study drug administration up to 90 days after the last dose of MEDI3617 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants who received treatment with MEDI3617. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 42 | 16 | 38 | 13 | 7 |
| Hematology: Anemia |
5
11.9%
|
1
6.3%
|
1
2.6%
|
3
23.1%
|
2
28.6%
|
| Hematology: Leukopenia |
0
0%
|
0
0%
|
0
0%
|
1
7.7%
|
2
28.6%
|
| Hematology: Neutropenia |
1
2.4%
|
0
0%
|
0
0%
|
0
0%
|
3
42.9%
|
| Hematology: Thombocytopenia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
28.6%
|
| Hematology: White blood cell count decreased |
2
4.8%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
| SerChem: Alanine aminotransferase increased |
0
0%
|
0
0%
|
1
2.6%
|
0
0%
|
0
0%
|
| SerChem: Aspartate aminotransferase increased |
0
0%
|
1
6.3%
|
2
5.3%
|
1
7.7%
|
0
0%
|
| SerChem: Blood alkaline phosphatase increased |
1
2.4%
|
0
0%
|
1
2.6%
|
1
7.7%
|
0
0%
|
| SerChem: Blood creatinine increased |
2
4.8%
|
1
6.3%
|
2
5.3%
|
1
7.7%
|
0
0%
|
| SerChem: Blood lactate dehydrogenase increased |
0
0%
|
0
0%
|
0
0%
|
1
7.7%
|
0
0%
|
| SerChem: Blood potassium increased |
0
0%
|
1
6.3%
|
0
0%
|
0
0%
|
0
0%
|
| SerChem: Blood triglycerides increased |
0
0%
|
1
6.3%
|
1
2.6%
|
0
0%
|
0
0%
|
| SerChem: Blood urea increased |
0
0%
|
0
0%
|
1
2.6%
|
0
0%
|
0
0%
|
| SerChem: Gamma-glutamyltransferase increased |
1
2.4%
|
1
6.3%
|
1
2.6%
|
1
7.7%
|
0
0%
|
| SerChem: Hyperglycaemia |
1
2.4%
|
0
0%
|
0
0%
|
1
7.7%
|
0
0%
|
| SerChem: Hyperkalaemia |
1
2.4%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| SerChem: Hypertriglyceridaemia |
0
0%
|
1
6.3%
|
0
0%
|
0
0%
|
0
0%
|
| SerChem: Hyperuricaemia |
1
2.4%
|
1
6.3%
|
0
0%
|
1
7.7%
|
0
0%
|
| SerChem: Hypoalbuminaemia |
0
0%
|
1
6.3%
|
1
2.6%
|
0
0%
|
0
0%
|
| SerChem: Hypocalcaemia |
0
0%
|
1
6.3%
|
0
0%
|
0
0%
|
0
0%
|
| SerChem: Hypoglycaemia |
1
2.4%
|
1
6.3%
|
2
5.3%
|
0
0%
|
0
0%
|
| SerChem: Hypokalaemia |
3
7.1%
|
0
0%
|
2
5.3%
|
0
0%
|
1
14.3%
|
| SerChem: Hypomagnesaemia |
1
2.4%
|
1
6.3%
|
0
0%
|
1
7.7%
|
3
42.9%
|
| SerChem: Hyponatremia |
0
0%
|
2
12.5%
|
1
2.6%
|
1
7.7%
|
2
28.6%
|
| Title | Number of Participants With Vital Sign Abnormalities Recorded as Adverse Events (AEs) |
|---|---|
| Description | Vital signs included parameters such as heart rate, blood pressure, temperature, weight and respiratory rate. An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to vital signs abnormalities were recorded and reported. |
| Time Frame | From start of study drug administration up to 90 days after the last dose of MEDI3617 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants who received treatment with MEDI3617. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 42 | 16 | 38 | 13 | 7 |
| Arrhythmia |
1
2.4%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Sinus tachycardia |
0
0%
|
1
6.3%
|
0
0%
|
1
7.7%
|
0
0%
|
| Tachycardia |
1
2.4%
|
1
6.3%
|
0
0%
|
1
7.7%
|
0
0%
|
| Pyrexia |
3
7.1%
|
3
18.8%
|
1
2.6%
|
0
0%
|
1
14.3%
|
| Weight decreased |
0
0%
|
2
12.5%
|
0
0%
|
0
0%
|
1
14.3%
|
| Weight increased |
9
21.4%
|
2
12.5%
|
0
0%
|
1
7.7%
|
0
0%
|
| Hypertension |
10
23.8%
|
7
43.8%
|
13
34.2%
|
3
23.1%
|
2
28.6%
|
| Hypotension |
0
0%
|
0
0%
|
1
2.6%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Echocardiogram Abnormalities Recorded as Adverse Events (AEs) |
|---|---|
| Description | An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to echocardiogram abnormalities were recorded and reported. The only AE reported was ejection fraction decreased in the MEDI3617 + Paclitaxel total group. |
| Time Frame | From start of study drug administration up to 90 days after the last dose of MEDI3617 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants who received treatment with MEDI3617. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 42 | 16 | 38 | 13 | 7 |
| Number [Participants] |
0
0%
|
0
0%
|
0
0%
|
1
7.7%
|
0
0%
|
| Title | Number of Participants With Electrocardiogram Abnormalities Recorded as Adverse Events (AEs) |
|---|---|
| Description | An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to electrocardiogram abnormalities were recorded and reported. The only AE reported was electrocardiogram QT prolonged in the MEDI3617 + Bevacizumab Q2W total group. |
| Time Frame | From start of study drug administration up to 90 days after the last dose of MEDI3617 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants who received treatment with MEDI3617 |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 42 | 16 | 38 | 13 | 7 |
| Number [Participants] |
0
0%
|
0
0%
|
1
2.6%
|
0
0%
|
0
0%
|
| Title | Maximum Observed Serum Concentration (Cmax) of MEDI3617 |
|---|---|
| Description | Cmax is the maximum observed serum concentration of MEDI3617. Here, "n" is number of participants analyzed for this endpoint at a specific dose. |
| Time Frame | Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment with MEDI3617 and for whom PK blood samples were collected and evaluated. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 41 | 16 | 35 | 13 | 7 |
| Cohort -2 (n=3) |
1.39
(0.254)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort -1 (n=2) |
2.44
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 1 (n=6) |
6.63
(3.48)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 2 (n=3) |
50.2
(28.8)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 3 (n=3) |
82.4
(2.68)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 4 (n=3) |
239
(79.5)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 5 (n=4) |
785
(189)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort ovarian cancer expansion (OCE) -1 (n=15) |
336
(62.2)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort OCE 1 (n=2) |
346
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 1A (n=4) |
NA
(NA)
|
30.4
(26.8)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 2A (n=3) |
NA
(NA)
|
55.3
(12.6)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 3A (n=3) |
NA
(NA)
|
235
(90.5)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 4A (n=6) |
NA
(NA)
|
348
(54.6)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 1B (n=7) |
NA
(NA)
|
NA
(NA)
|
44.5
(39.3)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 2B (n=3) |
NA
(NA)
|
NA
(NA)
|
47.5
(23.3)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 3B (n=8) |
NA
(NA)
|
NA
(NA)
|
116
(35.1)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 4B (n=8) |
NA
(NA)
|
NA
(NA)
|
275
(86.2)
|
NA
(NA)
|
NA
(NA)
|
| Cohort TT2A (n=9) |
NA
(NA)
|
NA
(NA)
|
320
(170)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MP1 (n=7) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
114
(22.5)
|
NA
(NA)
|
| Cohort MP2 (n=6) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
209
(57.4)
|
NA
(NA)
|
| Cohort MCP1 (n=4) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
200
(25.8)
|
| Cohort MCP2 (n=3) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
585
(491)
|
| Title | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI3617 |
|---|---|
| Description | AUC0-last is the Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration of MEDI3617. Here, "n" is number of participants analyzed for this endpoint at a specific dose. |
| Time Frame | Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment with MEDI3617 and for whom PK blood samples were collected and evaluated. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 41 | 16 | 35 | 13 | 7 |
| Cohort -2 (n=3) |
1.3
(0.429)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort -1 (n=2) |
2.2
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 1 (n=6) |
11.9
(11.8)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 2 (n=3) |
171
(69)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 3 (n=3) |
438
(204)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 4 (n=3) |
2610
(1570)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 5 (n=4) |
3650
(2600)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort OCE -1 (n=15) |
2610
(891)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort OCE 1 (n=2) |
2160
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 1A (n=4) |
NA
(NA)
|
101
(48.8)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 2A (n=3) |
NA
(NA)
|
473
(223)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 3A (n=3) |
NA
(NA)
|
2280
(529)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 4A (n=6) |
NA
(NA)
|
2710
(1070)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 1B (n=7) |
NA
(NA)
|
NA
(NA)
|
94.7
(48.7)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 2B (n=3) |
NA
(NA)
|
NA
(NA)
|
216
(61.8)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 3B (n=8) |
NA
(NA)
|
NA
(NA)
|
805
(292)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 4B (n=8) |
NA
(NA)
|
NA
(NA)
|
2310
(941)
|
NA
(NA)
|
NA
(NA)
|
| Cohort TT2A (n=9) |
NA
(NA)
|
NA
(NA)
|
2590
(1920)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MP1 (n=7) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
551
(331)
|
NA
(NA)
|
| Cohort MP2 (n=6) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
1460
(484)
|
NA
(NA)
|
| Cohort MCP1 (n=4) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
1240
(882)
|
| Cohort MCP2 (n=3) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
2890
(257)
|
| Title | Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of MEDI3617 |
|---|---|
| Description | The AUC0-inf is the Area Under the Concentration-Time Curve From Time Zero to infinity of MEDI3617. Here, "n" is number of participants analyzed for this endpoint at a specific dose. |
| Time Frame | Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment with MEDI3617 and for whom PK blood samples were collected and evaluated. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 25 | 8 | 13 | 4 | 3 |
| Cohort -2 (n=1) |
1.79
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 1 (n=1) |
8.12
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 2 (n=2) |
269
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 3 (n=3) |
529
(269)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 4 (n=2) |
2150
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 5 (n=2) |
4230
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort OCE -1 (n=12) |
3280
(1410)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort OCE 1 (n=2) |
2490
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 1A (n=3) |
NA
(NA)
|
110
(58.1)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 2A (n=3) |
NA
(NA)
|
628
(376)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 4A (n=2) |
NA
(NA)
|
3920
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 1B (n=7) |
NA
(NA)
|
NA
(NA)
|
104
(61)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 2B (n=3) |
NA
(NA)
|
NA
(NA)
|
252
(83.2)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 3B (n=2) |
NA
(NA)
|
NA
(NA)
|
1200
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 4B (n=1) |
NA
(NA)
|
NA
(NA)
|
4630
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MP1 (n=3) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
849
(163)
|
NA
(NA)
|
| Cohort MP2 (n=1) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
2810
(NA)
|
NA
(NA)
|
| Cohort MCP1 (n=1) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
2240
(NA)
|
| Cohort MCP2 (n=2) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
3560
(NA)
|
| Title | Systemic Clearance (CL) of MEDI3617 |
|---|---|
| Description | Systemic clearance describes the removal of drug from a volume of serum in a given unit of time (drug loss from the body). It is measured as milliliter per day (mL/day). Here, "n" is number of participants analyzed for this endpoint at a specific dose. |
| Time Frame | Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment with MEDI3617 and for whom PK blood samples were collected and evaluated. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 25 | 8 | 13 | 4 | 3 |
| Cohort -2 (n=1) |
2790
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 1 (n=1) |
2460
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 2 (n=2) |
423
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 3 (n=3) |
679
(345)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 4 (n=2) |
465
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 5 (n=2) |
355
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort OCE -1 (n=12) |
352
(136)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort OCE 1 (n=2) |
603
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 1A (n=3) |
NA
(NA)
|
1060
(426)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 2A (n=3) |
NA
(NA)
|
614
(363)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 4A (n=2) |
NA
(NA)
|
388
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 1B (n=7) |
NA
(NA)
|
NA
(NA)
|
797
(499)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 2B (n=3) |
NA
(NA)
|
NA
(NA)
|
847
(237)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 3B(n=2) |
NA
(NA)
|
NA
(NA)
|
501
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 4B (n=1) |
NA
(NA)
|
NA
(NA)
|
216
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MP1 (n=3) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
727
(157)
|
NA
(NA)
|
| Cohort MP2 (n=1) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
356
(NA)
|
NA
(NA)
|
| Cohort MCP1 (n=1) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
446
(NA)
|
| Cohort MCP2 (n=2) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
424
(NA)
|
| Title | Terminal Elimination Half Life (t1/2) of MEDI3617 |
|---|---|
| Description | The t1/2 is the time in days required for the concentration of the drug to reach half of its original value. Here, "n" is number of participants analyzed for this endpoint at a specific dose. |
| Time Frame | Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment with MEDI3617 and for whom PK blood samples were collected and evaluated. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 25 | 8 | 13 | 4 | 3 |
| Cohort -2 (n=1) |
0.585
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 1 (n=1) |
1.26
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 2 (n=2) |
5.86
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 3 (n=3) |
5.98
(3.09)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 4 (n=2) |
7.68
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort 5 (n=2) |
7.79
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort OCE -1 (n=12) |
10.4
(3.15)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort OCE 1 (n=2) |
9.03
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 1A (n=3) |
NA
(NA)
|
3.59
(0.983)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 2A (n=3) |
NA
(NA)
|
9.67
(3.35)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 4A (n=2) |
NA
(NA)
|
12.3
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 1B (n=7) |
NA
(NA)
|
NA
(NA)
|
3.9
(2.69)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 2B (n=3) |
NA
(NA)
|
NA
(NA)
|
5.12
(0.541)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 3B(n=2) |
NA
(NA)
|
NA
(NA)
|
8.23
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MB 4B (n=1) |
NA
(NA)
|
NA
(NA)
|
10.2
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cohort MP1 (n=3) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
6.96
(1.59)
|
NA
(NA)
|
| Cohort MP2 (n=1) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
9.34
(NA)
|
NA
(NA)
|
| Cohort MCP1 (n=1) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
15.1
(NA)
|
| Cohort MCP2 (n=2) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
11.1
(NA)
|
| Title | Number of Participants With Positive Anti-Drug Antibody (ADA) |
|---|---|
| Description | The immunogenic potential of MEDI3617 was assessed by summarizing the number and percentage of participants who develop detectable ADA. Immunogenicity assessment included determination of anti-drug (MEDI3617) antibodies in serum samples. Samples were measured for the presence of ADA using validated immunoassays. |
| Time Frame | Presence of ADA to MEDI3617 were assessed prior to infusion with MEDI3617 on Day 1 of each dosing cycle, as well as the end of treatment, and 30 days, 3 months, and 6 months post last dose of MEDI3617 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment with MEDI3617. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 42 | 16 | 38 | 13 | 7 |
| Number [participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Objective Response Rate (ORR) |
|---|---|
| Description | Objective response rate defined as the number of participants with confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to less than (<) 10 millimeter (the sum may not be "0" if there are target nodes). PR was defined as at least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. |
| Time Frame | Time from the first dose of investigational product until end of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants who received treatment with MEDI3617. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 42 | 16 | 38 | 13 | 7 |
| Number [Participants] |
1
2.4%
|
1
6.3%
|
2
5.3%
|
2
15.4%
|
0
0%
|
| Title | Time to Response (TTR) |
|---|---|
| Description | Time to response (TTR) is defined as the time from the study entry to the first documentation of confirmed CR or confirmed PR. CR was defined as disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to less than (<) 10 millimeter (the sum may not be "0" if there are target nodes). PR was defined as at least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Analysis was based on responses confirmed at a repeat assessment made at least 4 weeks after the initial response, with the TTR taken as the first time the response was observed, not the confirmation assessment. TTR was evaluated using the Kaplan-Meier method. |
| Time Frame | Time from the first dose of investigational product until end of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants who received treatment with MEDI3617. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 42 | 16 | 38 | 13 | 7 |
| Median (Full Range) [months] |
2.6
|
1.2
|
2.0
|
1.7
|
NA
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | Duration of response is defined as the duration from the first documentation of objective disease response (ie, confirmed CR or confirmed PR) to the first documented disease progression. The duration of response was censored on the date of last tumor assessment documenting absence of disease progression for participants who have no documented progression prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. Duration of response was evaluated for the subgroup of participants with an objective response using the Kaplan-Meier method. |
| Time Frame | Time from the first dose of investigational product until end of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants who received treatment with MEDI3617. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 42 | 16 | 38 | 13 | 7 |
| Median (Full Range) [months] |
3.7
|
NA
|
NA
|
NA
|
NA
|
| Title | Time to Progression (TTP) |
|---|---|
| Description | Time to progression (TTP) is defined as time from the start of treatment with MEDI3617 until the documentation of disease progression. The TTP was censored on the date of last tumor assessment documenting absence of tumor progression for participants who have no documented progression prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. Participants having no tumor assessments after the start of treatment with MEDI3617 had TTP censored on the first date of treatment with MEDI3617. TTP was evaluated using the Kaplan-Meier method. |
| Time Frame | Time from the first dose of investigational product until end of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants who received treatment with MEDI3617. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 42 | 16 | 38 | 13 | 7 |
| Median (Full Range) [months] |
1.4
|
11.4
|
1.8
|
3.5
|
NA
|
| Title | Progression-Free Survival (PFS) |
|---|---|
| Description | PFS was measured from the start of treatment with MEDI3617 until the documentation of disease progression or death due to any cause, whichever occurred first. PFS was censored on the date of last tumor assessment documenting absence of tumor progression for participants who have no documented progression and were still alive prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. Participants having no tumor assessments after the start of treatment with MEDI3617 had PFS censored on the first date of treatment with MEDI3617. PFS was evaluated using the Kaplan-Meier method. |
| Time Frame | Time from the first dose of investigational product until end of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants who received treatment with MEDI3617. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 42 | 16 | 38 | 13 | 7 |
| Median (Full Range) [months] |
1.4
|
11.4
|
1.7
|
3.5
|
NA
|
| Title | Overall Survival (OS) |
|---|---|
| Description | Overall survival is defined as the time from the start of treatment with MEDI3617 until death. For the participants who were alive at the end of study or lost to follow-up, overall survival was censored on the last date when participants were known to be alive. Overall survival was evaluated using the Kaplan-Meier method. |
| Time Frame | Time from the first dose of investigational product until death due to any cause |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants who received treatment with MEDI3617. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 42 | 16 | 38 | 13 | 7 |
| Median (Full Range) [months] |
11.4
|
25.7
|
7.4
|
14.2
|
NA
|
| Title | Circulating Levels of Angiopoietin 2 (Ang2) |
|---|---|
| Description | Profile of Ang2 post MEDI3617 administration in relation to time course of antibody concentrations. |
| Time Frame | Prior to infusion on Cycle 4 and Cycle 5 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment with MEDI3617 and for whom PD blood samples were collected and evaluated. |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 14 | 11 | 7 | 3 | 2 |
| Cycle 4: Cohort -2 (n=2) |
4.07
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 5: Cohort -2 (n=2) |
4.28
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 4: Cohort -1 (n=2) |
5.11
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 4: Cohort 1 (n=3) |
5.69
(4.02)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 5: Cohort 1 (n=2) |
8.22
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 4: Cohort 2 (n=1) |
307.53
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 5: Cohort 2 (n=1) |
924.66
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 4: Cohort 3 (n=1) |
341.21
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 5: Cohort 3 (n=1) |
265.86
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 4: Cohort 4 (n=1) |
288.10
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 4: Cohort 5 (n=1) |
1181.14
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 5: Cohort 5 (n=1) |
1451.43
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 4: Cohort OCE -1 (n=3) |
312.27
(151.19)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 5: Cohort OCE -1 (n=3) |
206.43
(83.74)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 4: Cohort MB 1A (n=2) |
NA
(NA)
|
386.13
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 5: Cohort MB 1A (n=2) |
NA
(NA)
|
421.74
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 4: Cohort MB 2A (n=3) |
NA
(NA)
|
215.71
(143.16)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 5: Cohort MB 2A (n=2) |
NA
(NA)
|
228.92
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 4: Cohort MB 3A (n=1) |
NA
(NA)
|
218.48
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 5: Cohort MB 3A (n=2) |
NA
(NA)
|
247.51
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 4: Cohort MB 4A (n=4) |
NA
(NA)
|
368.08
(257.59)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 5: Cohort MB 4A (n=2) |
NA
(NA)
|
353.73
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 4: Cohort MB 1B (n=2) |
NA
(NA)
|
NA
(NA)
|
466.27
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 5: Cohort MB 1B (n=1) |
NA
(NA)
|
NA
(NA)
|
750.61
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 4: Cohort MB 2B (n=1) |
NA
(NA)
|
NA
(NA)
|
421.03
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 5: Cohort MB 2B (n=1) |
NA
(NA)
|
NA
(NA)
|
387.45
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 4:Cohort MB 3B (n=1) |
NA
(NA)
|
NA
(NA)
|
141.93
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 4: Cohort MB 4B (n=3) |
NA
(NA)
|
NA
(NA)
|
229.19
(109.02)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 5: Cohort MB 4B (n=1) |
NA
(NA)
|
NA
(NA)
|
174.65
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 4: Cohort MP1 (n=1) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
339.35
(NA)
|
NA
(NA)
|
| Cycle 4: Cohort MP2 (n=2) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
210.43
(NA)
|
NA
(NA)
|
| Cycle 5: Cohort MP2 (n=2) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
166.73
(NA)
|
NA
(NA)
|
| Cycle 4: Cohort MCP1 (n=2) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
348.53
(NA)
|
| Cycle 5: Cohort MCP1 (n=2) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
336.31
(NA)
|
| Title | Number of Participants With a Decline in Karnofsky Performance Status (KPS) of ≥ 20 Points at Worst Record On-study Compared With Baseline |
|---|---|
| Description | KPS scale: 100 is no evidence of disease; 90 is able to carry on normal activity, minor symptoms of disease; 80 is normal activity with effort, some symptoms of disease; 70 is cares for self; unable to do active work; 60 is requires occasional assistance, but is able to care for most of his needs; 50 is requires considerable assistance with frequent medical care; 40 is disabled, requires special care; 30 is severely disabled, hospitalization is indicated although death is not imminent; 20 is very sick, hospitalization necessary, active support treatment necessary; 10 is moribund, fatal processes progressing rapidly, 0 is dead. |
| Time Frame | From start of study drug administration up to 30 days after the last dose of MEDI3617 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants who received treatment with MEDI3617 |
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
| Measure Participants | 42 | 16 | 38 | 13 | 7 |
| Number [Participants] |
11
26.2%
|
6
37.5%
|
7
18.4%
|
1
7.7%
|
1
14.3%
|
Adverse Events
| Time Frame | From start of study drug administration up to 90 days after the last dose of MEDI3617 | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL | |||||
| Arm/Group Description | Participants received MEDI3617 via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. | Participants received MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. | Participants received MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. | |||||
All Cause Mortality |
||||||||||
| MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL | ||||||
| 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) | |||||
Serious Adverse Events |
||||||||||
| MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 18/42 (42.9%) | 4/16 (25%) | 18/38 (47.4%) | 7/13 (53.8%) | 4/7 (57.1%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Neutropenia | 1/42 (2.4%) | 3 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Cardiac disorders | ||||||||||
| Atrial fibrillation | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Cardiac arrest | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||
| Abdominal pain | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Ascites | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 1/7 (14.3%) | 1 |
| Dysphagia | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Faecal incontinence | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Intestinal obstruction | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Nausea | 2/42 (4.8%) | 2 | 0/16 (0%) | 0 | 1/38 (2.6%) | 2 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Pancreatitis acute | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Small intestinal obstruction | 3/42 (7.1%) | 3 | 0/16 (0%) | 0 | 1/38 (2.6%) | 2 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Vomiting | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 1/38 (2.6%) | 2 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| General disorders | ||||||||||
| Asthenia | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Medical device pain | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Oedema | 2/42 (4.8%) | 2 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Oedema peripheral | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Pyrexia | 1/42 (2.4%) | 1 | 1/16 (6.3%) | 1 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Immune system disorders | ||||||||||
| Anaphylactic reaction | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 1/7 (14.3%) | 1 |
| Drug hypersensitivity | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 1/7 (14.3%) | 1 |
| Infections and infestations | ||||||||||
| Abscess limb | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Meningitis | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Pneumonia | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 1/13 (7.7%) | 1 | 1/7 (14.3%) | 1 |
| Urinary tract infection | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||
| Infusion related reaction | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 1/7 (14.3%) | 1 |
| Investigations | ||||||||||
| Blood alkaline phosphatase increased | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Blood creatinine increased | 2/42 (4.8%) | 2 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Ejection fraction decreased | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Troponin increased | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Weight increased | 2/42 (4.8%) | 2 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||
| Decreased appetite | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Dehydration | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 1/7 (14.3%) | 2 |
| Failure to thrive | 0/42 (0%) | 0 | 1/16 (6.3%) | 1 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Back pain | 2/42 (4.8%) | 2 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Groin pain | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Muscular weakness | 0/42 (0%) | 0 | 1/16 (6.3%) | 1 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Pain in extremity | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Glioblastoma | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 3/38 (7.9%) | 3 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Nervous system disorders | ||||||||||
| Aphasia | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Ataxia | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Cerebrovascular accident | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Cognitive disorder | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Encephalopathy | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Headache | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Hemiparesis | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 3/38 (7.9%) | 3 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Ischaemic stroke | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Memory impairment | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Posterior reversible encephalopathy syndrome | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Seizure | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 2/38 (5.3%) | 2 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Syncope | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Psychiatric disorders | ||||||||||
| Confusional state | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 2/13 (15.4%) | 2 | 0/7 (0%) | 0 |
| Renal and urinary disorders | ||||||||||
| Dysuria | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Nephrotic syndrome | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 1/7 (14.3%) | 1 |
| Renal failure | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Urinary incontinence | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Urinary tract obstruction | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||
| Female genital tract fistula | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 2/38 (5.3%) | 2 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Pelvic pain | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Acute respiratory failure | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Chronic obstructive pulmonary disease | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Chylothorax | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Dyspnoea | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Pleural effusion | 4/42 (9.5%) | 4 | 2/16 (12.5%) | 3 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Pneumonitis | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Pneumothorax | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Pulmonary embolism | 2/42 (4.8%) | 2 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Pulmonary haemorrhage | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Respiratory failure | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Vascular disorders | ||||||||||
| Deep vein thrombosis | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Embolism | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Haematoma | 0/42 (0%) | 0 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Hypertension | 1/42 (2.4%) | 1 | 1/16 (6.3%) | 1 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Lymphoedema | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||
| MEDI3617 SINGLE AGENT TOTAL | MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL | MEDI3617 + BEVACIZUMAB Q2W TOTAL | MEDI3617 + PACLITAXEL TOTAL | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 40/42 (95.2%) | 16/16 (100%) | 34/38 (89.5%) | 13/13 (100%) | 7/7 (100%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 4/42 (9.5%) | 5 | 1/16 (6.3%) | 1 | 1/38 (2.6%) | 1 | 2/13 (15.4%) | 2 | 2/7 (28.6%) | 3 |
| Cardiac disorders | ||||||||||
| Atrial fibrillation | 3/42 (7.1%) | 3 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 2/13 (15.4%) | 2 | 0/7 (0%) | 0 |
| Eye disorders | ||||||||||
| Vision blurred | 3/42 (7.1%) | 3 | 1/16 (6.3%) | 1 | 1/38 (2.6%) | 1 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||
| Abdominal distension | 3/42 (7.1%) | 4 | 1/16 (6.3%) | 1 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Abdominal pain | 7/42 (16.7%) | 7 | 2/16 (12.5%) | 2 | 3/38 (7.9%) | 3 | 1/13 (7.7%) | 1 | 1/7 (14.3%) | 1 |
| Ascites | 3/42 (7.1%) | 3 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Constipation | 16/42 (38.1%) | 19 | 9/16 (56.3%) | 12 | 4/38 (10.5%) | 4 | 4/13 (30.8%) | 6 | 1/7 (14.3%) | 1 |
| Diarrhoea | 8/42 (19%) | 11 | 5/16 (31.3%) | 7 | 3/38 (7.9%) | 4 | 4/13 (30.8%) | 4 | 1/7 (14.3%) | 1 |
| Dry mouth | 7/42 (16.7%) | 7 | 2/16 (12.5%) | 3 | 1/38 (2.6%) | 1 | 1/13 (7.7%) | 1 | 1/7 (14.3%) | 1 |
| Dyspepsia | 4/42 (9.5%) | 4 | 1/16 (6.3%) | 1 | 1/38 (2.6%) | 1 | 2/13 (15.4%) | 2 | 0/7 (0%) | 0 |
| Dysphagia | 1/42 (2.4%) | 1 | 1/16 (6.3%) | 1 | 2/38 (5.3%) | 2 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Gingival pain | 1/42 (2.4%) | 1 | 2/16 (12.5%) | 2 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Nausea | 11/42 (26.2%) | 13 | 8/16 (50%) | 14 | 11/38 (28.9%) | 13 | 4/13 (30.8%) | 6 | 4/7 (57.1%) | 5 |
| Vomiting | 11/42 (26.2%) | 14 | 5/16 (31.3%) | 8 | 3/38 (7.9%) | 5 | 2/13 (15.4%) | 2 | 2/7 (28.6%) | 3 |
| General disorders | ||||||||||
| Chills | 4/42 (9.5%) | 4 | 1/16 (6.3%) | 1 | 3/38 (7.9%) | 3 | 0/13 (0%) | 0 | 1/7 (14.3%) | 1 |
| Fatigue | 18/42 (42.9%) | 26 | 10/16 (62.5%) | 13 | 12/38 (31.6%) | 13 | 5/13 (38.5%) | 6 | 3/7 (42.9%) | 5 |
| Mucosal inflammation | 2/42 (4.8%) | 2 | 2/16 (12.5%) | 5 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Oedema peripheral | 11/42 (26.2%) | 15 | 2/16 (12.5%) | 12 | 7/38 (18.4%) | 16 | 4/13 (30.8%) | 7 | 0/7 (0%) | 0 |
| Pyrexia | 2/42 (4.8%) | 3 | 2/16 (12.5%) | 3 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 1/7 (14.3%) | 1 |
| Immune system disorders | ||||||||||
| Drug hypersensitivity | 0/42 (0%) | 0 | 1/16 (6.3%) | 1 | 1/38 (2.6%) | 1 | 2/13 (15.4%) | 2 | 0/7 (0%) | 0 |
| Infections and infestations | ||||||||||
| Upper respiratory tract infection | 1/42 (2.4%) | 1 | 2/16 (12.5%) | 2 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Urinary tract infection | 0/42 (0%) | 0 | 2/16 (12.5%) | 2 | 2/38 (5.3%) | 2 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||
| Contusion | 1/42 (2.4%) | 1 | 3/16 (18.8%) | 3 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Investigations | ||||||||||
| Aspartate aminotransferase increased | 0/42 (0%) | 0 | 1/16 (6.3%) | 1 | 2/38 (5.3%) | 2 | 1/13 (7.7%) | 2 | 0/7 (0%) | 0 |
| Blood creatinine increased | 0/42 (0%) | 0 | 1/16 (6.3%) | 1 | 2/38 (5.3%) | 2 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Gamma-glutamyltransferase increased | 1/42 (2.4%) | 1 | 1/16 (6.3%) | 1 | 1/38 (2.6%) | 1 | 1/13 (7.7%) | 2 | 0/7 (0%) | 0 |
| Weight increased | 8/42 (19%) | 11 | 2/16 (12.5%) | 15 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||
| Decreased appetite | 8/42 (19%) | 11 | 5/16 (31.3%) | 6 | 5/38 (13.2%) | 7 | 1/13 (7.7%) | 3 | 2/7 (28.6%) | 2 |
| Dehydration | 2/42 (4.8%) | 2 | 2/16 (12.5%) | 2 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 1/7 (14.3%) | 1 |
| Hypoglycaemia | 1/42 (2.4%) | 1 | 1/16 (6.3%) | 6 | 2/38 (5.3%) | 2 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Hypokalaemia | 3/42 (7.1%) | 8 | 0/16 (0%) | 0 | 2/38 (5.3%) | 3 | 0/13 (0%) | 0 | 1/7 (14.3%) | 1 |
| Hypomagnesaemia | 1/42 (2.4%) | 1 | 1/16 (6.3%) | 1 | 0/38 (0%) | 0 | 1/13 (7.7%) | 2 | 3/7 (42.9%) | 3 |
| Hyponatraemia | 0/42 (0%) | 0 | 2/16 (12.5%) | 2 | 1/38 (2.6%) | 1 | 1/13 (7.7%) | 1 | 2/7 (28.6%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 3/42 (7.1%) | 5 | 4/16 (25%) | 4 | 1/38 (2.6%) | 2 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Back pain | 2/42 (4.8%) | 2 | 2/16 (12.5%) | 2 | 2/38 (5.3%) | 2 | 2/13 (15.4%) | 2 | 0/7 (0%) | 0 |
| Muscle spasms | 3/42 (7.1%) | 3 | 1/16 (6.3%) | 1 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Muscular weakness | 1/42 (2.4%) | 1 | 1/16 (6.3%) | 1 | 3/38 (7.9%) | 4 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Musculoskeletal chest pain | 2/42 (4.8%) | 2 | 3/16 (18.8%) | 4 | 1/38 (2.6%) | 1 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Musculoskeletal pain | 0/42 (0%) | 0 | 2/16 (12.5%) | 2 | 3/38 (7.9%) | 3 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Myalgia | 8/42 (19%) | 8 | 4/16 (25%) | 9 | 2/38 (5.3%) | 2 | 1/13 (7.7%) | 1 | 1/7 (14.3%) | 1 |
| Pain in extremity | 2/42 (4.8%) | 3 | 8/16 (50%) | 10 | 4/38 (10.5%) | 4 | 1/13 (7.7%) | 2 | 1/7 (14.3%) | 1 |
| Nervous system disorders | ||||||||||
| Ataxia | 1/42 (2.4%) | 1 | 1/16 (6.3%) | 1 | 2/38 (5.3%) | 2 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Dizziness | 13/42 (31%) | 14 | 7/16 (43.8%) | 10 | 2/38 (5.3%) | 2 | 2/13 (15.4%) | 6 | 1/7 (14.3%) | 1 |
| Dysgeusia | 4/42 (9.5%) | 5 | 1/16 (6.3%) | 1 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 2/7 (28.6%) | 2 |
| Headache | 7/42 (16.7%) | 8 | 4/16 (25%) | 6 | 7/38 (18.4%) | 8 | 1/13 (7.7%) | 1 | 1/7 (14.3%) | 1 |
| Hypoaesthesia | 1/42 (2.4%) | 1 | 0/16 (0%) | 0 | 2/38 (5.3%) | 2 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Neuropathy peripheral | 4/42 (9.5%) | 4 | 2/16 (12.5%) | 2 | 3/38 (7.9%) | 5 | 4/13 (30.8%) | 5 | 2/7 (28.6%) | 2 |
| Paraesthesia | 3/42 (7.1%) | 3 | 2/16 (12.5%) | 2 | 2/38 (5.3%) | 2 | 0/13 (0%) | 0 | 1/7 (14.3%) | 1 |
| Psychiatric disorders | ||||||||||
| Anxiety | 3/42 (7.1%) | 3 | 4/16 (25%) | 6 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Depression | 2/42 (4.8%) | 2 | 3/16 (18.8%) | 4 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Insomnia | 0/42 (0%) | 0 | 4/16 (25%) | 5 | 4/38 (10.5%) | 4 | 2/13 (15.4%) | 2 | 0/7 (0%) | 0 |
| Renal and urinary disorders | ||||||||||
| Proteinuria | 2/42 (4.8%) | 5 | 1/16 (6.3%) | 3 | 5/38 (13.2%) | 14 | 0/13 (0%) | 0 | 1/7 (14.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Cough | 9/42 (21.4%) | 9 | 4/16 (25%) | 5 | 2/38 (5.3%) | 3 | 2/13 (15.4%) | 2 | 0/7 (0%) | 0 |
| Dysphonia | 4/42 (9.5%) | 4 | 1/16 (6.3%) | 1 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Dyspnoea | 9/42 (21.4%) | 12 | 3/16 (18.8%) | 4 | 4/38 (10.5%) | 4 | 3/13 (23.1%) | 3 | 0/7 (0%) | 0 |
| Dyspnoea exertional | 0/42 (0%) | 0 | 2/16 (12.5%) | 5 | 2/38 (5.3%) | 3 | 2/13 (15.4%) | 2 | 0/7 (0%) | 0 |
| Nasal congestion | 3/42 (7.1%) | 3 | 1/16 (6.3%) | 1 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 1/7 (14.3%) | 1 |
| Oropharyngeal pain | 1/42 (2.4%) | 1 | 2/16 (12.5%) | 2 | 1/38 (2.6%) | 1 | 1/13 (7.7%) | 1 | 2/7 (28.6%) | 2 |
| Pleural effusion | 4/42 (9.5%) | 4 | 2/16 (12.5%) | 4 | 0/38 (0%) | 0 | 3/13 (23.1%) | 4 | 1/7 (14.3%) | 1 |
| Productive cough | 1/42 (2.4%) | 1 | 1/16 (6.3%) | 1 | 2/38 (5.3%) | 2 | 1/13 (7.7%) | 2 | 0/7 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Alopecia | 2/42 (4.8%) | 2 | 0/16 (0%) | 0 | 0/38 (0%) | 0 | 3/13 (23.1%) | 4 | 0/7 (0%) | 0 |
| Dry skin | 1/42 (2.4%) | 1 | 2/16 (12.5%) | 2 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 1/7 (14.3%) | 2 |
| Night sweats | 3/42 (7.1%) | 3 | 1/16 (6.3%) | 1 | 0/38 (0%) | 0 | 1/13 (7.7%) | 1 | 0/7 (0%) | 0 |
| Pruritus | 2/42 (4.8%) | 2 | 2/16 (12.5%) | 4 | 0/38 (0%) | 0 | 0/13 (0%) | 0 | 0/7 (0%) | 0 |
| Rash | 3/42 (7.1%) | 3 | 0/16 (0%) | 0 | 1/38 (2.6%) | 1 | 0/13 (0%) | 0 | 1/7 (14.3%) | 1 |
| Vascular disorders | ||||||||||
| Hypertension | 10/42 (23.8%) | 12 | 6/16 (37.5%) | 24 | 13/38 (34.2%) | 16 | 3/13 (23.1%) | 3 | 2/7 (28.6%) | 5 |
Limitations/Caveats
[Not Specified]
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" in the agreement description.
Results Point of Contact
| Name/Title | Mohammed Dar, MD |
|---|---|
| Organization | MedImmune, LLC |
| Phone | 301-398-0000 |
| information.center@astrazeneca.com |
Responsible Party:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01248949
Other Study ID Numbers:
- CD-ON-MEDI3617-1043
First Posted:
Nov 25, 2010
Last Update Posted:
Mar 29, 2017
Last Verified:
Feb 1, 2017