Carcinoma, Hepatocellular
Conditions
Keywords
advanced hepatocellular carcinoma, Mapatumumab, HGS1012, sorafenib
Brief summary
Mapatumumab is a fully human, agonist monoclonal antibody that activates the cell death pathway in tumor cells by specifically binding to TRAIL-R1 with high affinity. Sorafenib, a multikinase inhibitor, is the standard of care for treatment of patients with advanced hepatocellular carcinoma (HCC). The mechanisms of sorafenib and mapatumumab action suggest that these agents could interact synergistically. This is a Phase 2, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of mapatumumab in combination with sorafenib in subjects with advanced hepatocellular carcinoma.
Interventions
DRUGMapatumumab
Mapatumumab will be supplied as a lyophilized formulation in 10 mL vials containing 100 mg mapatumumab for intravenous infusion at the dose of 30 mg/kg.
DRUGPlacebo
Normal saline solution for intravenous infusion will be administered as placebo for mapatumumab
DRUGSorafenib
Sorafenib will be supplied as tablets, each containing 274 mg sorafenib tosylate, equivalent to 200 mg of sorafenib, to be administered 400 mg (2 x 200 mg tablets) orally twice daily.
Sponsors
GlaxoSmithKline
Human Genome Sciences Inc., a GSK Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Child-Pugh Class A. * Barcelona Clinic Liver Cancer (BCLC) advanced stage (C) hepatocellular carcinoma, or BCLC intermediate stage (B) hepatocellular carcinoma if treatment with transarterial chemoembolization is not considered appropriate * Measurable disease demonstrating intratumoral arterial enhancement by contrast enhanced computerized tomography (CT), with use of multislice scanners, or contrast enhanced dynamic magnetic resonance imaging (MRI), with at least 1 tumor lesion that meets the following criteria: located in the liver; can be accurately measured in at least 1 dimension; well delineated area of viable, hypervascular (contrast enhancement in the arterial phase) tumor that is \>2 centimeter (cm) in the axial plane; suitable for repeat measurement; OR not previously treated with locoregional or systemic treatment unless the lesion shows a well-delineated area of viable (contrast enhancement in the arterial phase) tumor that is \>2 cm in the axial plane. (If the lesion is poorly demarcated or exhibits atypical enhancement as a result of the previous intervention, then it cannot be selected as a target lesion) * Radiologic eligibility (measurable disease) must be must be confirmed by the BICR prior to randomization. * Adequate bone marrow, renal and liver function as defined in the protocol. * Performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) Scale * Age 18 years or older * Have the ability to understand the requirements of the study, provide written informed consent (including consent for the use and disclosure of research-related health information), and comply with the study and follow-up procedures.
Exclusion criteria
* Any co-morbid condition that in the judgment of the investigator renders the subject at high risk of treatment complications or reduces the possibility of assessing clinical effect. * Received prior investigational or non-investigational cytotoxic chemotherapy, hormonal therapy, biological therapy (including but not limited to monoclonal antibodies, small molecules or other immunotherapy) to treat hepatocellular carcinoma. * History of organ allograft. * Previously received mapatumumab or sorafenib. * Underwent resection, radiofrequency ablation, radiation or chemoembolization within 4 weeks before enrollment or not recovered from such treatments. * Need for concomitant anticancer therapy (surgery, radiation therapy, chemotherapy, immunotherapy, radiofrequency ablation) or other investigational agents during the study treatment period. * Major surgery (i.e., the opening of a major body cavity, requiring the use of general anesthesia) within 4 weeks before enrollment; minor surgery (except for insertion of vascular access device) within 2 weeks before enrollment; or not yet recovered from the effects of the surgery. * Systemic steroids within 1 week before enrollment except steroids used as part of an antiemetic regimen or maintenance-dose steroids for non-cancerous disease. * Hepatic encephalopathy, per the investigator's evaluation. * History of clinically significant gastrointestinal bleeding requiring procedural intervention (e.g., variceal banding, transjugular intrahepatic portosystemic shunt procedure, arterial embolization, topical coagulation therapy) within 4 weeks before enrollment. * Gastrointestinal disease resulting in an inability to take oral medication or a requirement for intravenous hyperalimentation. * History of any infection requiring hospitalization or intravenous antibiotics within 2 weeks before enrollment. * Known brain or spinal cord metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids. * Known human immunodeficiency virus infection. * Unstable angina, myocardial infarction, cerebrovascular accident, \>= Class II congestive heart failure according to the New York Heart Association Classification for Congestive Heart Failure within 6 months before enrollment. * Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin. * Uncontrolled hypertension (systolic blood pressure \>150 millimeters of mercury \[mmHg\] or diastolic pressure \>90 mmHg despite optimal medical management). * Using and unable to discontinue use of concomitant strong CYP3A4 inducers (e.g., including but not limited to St. John's Wort, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital) * Pregnant female or nursing mother. All females with an intact uterus (unless amenorrheic for the 24 months before enrollment) must have a negative serum pregnancy test at screening. All non-sterile or non-postmenopausal females must practice a medically accepted method of contraception over the course of the study and for 60 days after the last dose of study agent. * Males who do not agree to use effective contraception during the study and for a period of 60 days following the final dose of study agent. * Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s) or subject is receiving other investigational agents. * Acute or chronic severe renal insufficiency (glomoerular filtration rate \<30 milliliters \[mL\]/minute/1.73 square meters) or acute renal insufficiency of any severity due to the hepato-renal syndrome. * Hepatitis B virus deoxyribonucleic acid (DNA) levels \>2,000 international units/mL.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression-Blinded Independent Central Review (BICR) Assessment | Randomization to maximum of 24.1 months | Time to progression is defined as the time from randomization to radiologic disease progression based on blinded independent review (BICR) of imaging scans using modified Response Evaluation Criteria in Solid Tumors assessment (mRECIST) for hepatocellular carcinoma. The primary analysis was performed using Kaplan Meier methods. The median time to progression is reported with one-sided 90% confidence interval. Analysis was performed on the modified Intent to Treat (mITT) Population which comprised of all randomized participants who received at least part of 1 dose of study agent (mapatumumab/placebo and/or sorafenib) with participants analyzed according to the groups to which they were randomized. NA indicates upper limit was not measurable as one-sided confidence interval is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival | Randomization to maximum of 52.9 months | Overall survival is defined as time from randomization to death from any cause. The analysis was performed using Kaplan Meier methods. The median overall survival is reported with one-sided 90% confidence interval. NA indicates upper limit was not measurable as one-sided confidence interval is presented. |
| Progression Free Survival-BICR Assessment | Randomization to maximum of 24.1 months | Progression free survival is defined as time from randomization to radiologic disease progression or death from any cause. The analysis was performed using Kaplan Meier methods using BICR assessment of imaging scans. The median progression free survival is reported with one-sided 90% confidence interval. NA indicates upper limit was not measurable as one-sided confidence interval is presented. |
| Progression Free Survival-Investigator Assessment | Randomization to maximum of 52.9 months | Progression free survival is defined as time from randomization to radiologic disease progression or death from any cause. The analysis was performed using Kaplan Meier methods based on application of mRECIST for hepatocellular carcinoma to investigator assessments. The median progression free survival is reported with one-sided 90% confidence interval. NA indicates upper limit was not measurable as one-sided confidence interval is presented. |
| Percentage of Participants With Objective Response-BICR Assessment | Randomization to maximum of 24.1 months | Objective response rate is defined as the percentage of participants with complete response+partial response according to mRECIST criteria for hepatocellular carcinoma using BICR assessment of imaging scans. The percentage of participants with objective response is reported along with 95% confidence interval. |
| Percentage of Participants With Objective Response-Investigator Assessment | Randomization to maximum of 52.9 months | Objective response rate is defined as the percentage of participants with complete response+partial response according to mRECIST criteria for hepatocellular carcinoma to investigator assessments. The percentage of participants with objective response is reported along with 95% confidence interval. |
| Percentage of Participants With Disease Control-BICR Assessment | Randomization to maximum of 24.1 months | Disease control rate is the percentage of participants with complete response+partial response+stable disease according to mRECIST criteria for hepatocellular carcinoma. The end point was based on BICR assessment of imaging scans. The percentage of participants with disease control is presented along with 95% confidence interval. |
| Percentage of Participants With Disease Control-Investigator Assessment | Randomization to maximum of 52.9 months | Disease control rate is the percentage of participants with complete response+partial response+stable disease according to mRECIST criteria for hepatocellular carcinoma to investigator assessments. The percentage of participants with disease control is presented along with 95% confidence interval. |
| Time to Response-BICR Assessment | Randomization to maximum of 24.1 months | Time to response is defined as time from randomization to first partial response or complete response in responders only. Complete Response (CR): Disappearance of intratumoral arterial enhancement in all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions |
| Duration of Response-BICR Assessment | Randomization to maximum of 24.1 months | Duration of response is defined as time from first PR or CR to radiologic disease progression; in responders only. CR: Disappearance of intratumoral arterial enhancement in all target lesions. PR: At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the Baseline sum of the diameters of target lesions. Progressive disease (PD): An increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started. |
| Number of Participants With Treatment-emergent Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) | Start of study treatment to maximum of 52.9 months | An AE is any unfavorable or unintended sign, symptom, or disease that is temporally associated with the use of a study agent but is not necessarily caused by the study agent. An SAE is an adverse event resulting in any of the following outcomes: death, life-threatening, inpatient hospitalization, prolongation of an existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect or other medically important events that may jeopardize the participant or may require intervention to prevent one of the other outcomes mentioned before. A treatment-emergent AE is an AE that emerged during treatment, having been absent pre-treatment, or worsened relative to the pre-treatment state. As-Treated Population comprised of participants who received at least part of 1 dose of study agent analyzed according to the treatment that they actually received. |
| Time to Progression-Investigator Assessment | Randomization to maximum of 52.9 months | Time to progression is defined as the time from randomization to radiologic disease progression. The primary analysis was performed using Kaplan Meier methods based on application of mRECIST for hepatocellular carcinoma to investigator assessments. The median time to progression is reported with one-sided 90% confidence interval. NA indicates upper limit was not measurable as one-sided confidence interval is presented. |
| Number of Participants With Worst Toxicity Grade-chemistry Parameters | Enrolment to maximum of 52.9 months | Blood samples were collected for the evaluation of following chemistry parameters: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), amylase, bilirubin, gamma glutamyl transferase (GGT), calcium, potassium, magnesium, albumin, sodium and creatinine. Laboratory toxicities were graded based on the NCI-CTCAE version 4.0. Grade 1 represents mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 represents moderate; minimal, local or non-invasive intervention indicated. Grade 3 represents severe or medically significant but not immediately life -threatening; hospitalization or prolongation of hospitalization indicated; disabling. Grade 4 represents life -threatening consequences; urgent intervention indicated. Number of participants with worst toxicity grades for any abnormalities observed in any chemistry parameters during the study is presented. |
| Number of Participants With Worst Toxicity Grade-hematology Parameters | Enrolment to maximum of 52.9 months | Blood samples were collected for assessment of the following hematology parameters: activated partial thromboplastin time (APTT), hemoglobin, international normalized ratio (INR), lymphocytes, neutrophils, platelets and white blood cells (WBC). Laboratory toxicities were graded based on the NCI-CTCAE version 4.0. Grade 1 represents mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 represents moderate; minimal, local or non-invasive intervention indicated. Grade 3 represents severe or medically significant but not immediately life -threatening; hospitalization or prolongation of hospitalization indicated; disabling. Grade 4 represents life -threatening consequences; urgent intervention indicated. Number of participants with worst toxicity grades for any abnormalities observed in any hematology parameters during the study is presented. |
| Number of Participants With Anti-mapatumumab Antibodies | Randomization to maximum of 24.1 months | Blood samples were collected for the assessment of serum antibodies. The presence of anti-mapatumumab antibodies was assessed using a validated electrochemiluminescent immunoassay. The assay incorporated a tiered testing approach which used screening and confirmation steps. The anti-drug antibody (ADA) confirmed positive participants were separated into transient or persistent antibody positives. Persistent positive refers to positive immunogenic response at 2 or more assessments or at the final assessment. Transient positive refers to positive immunogenic response at only 1 assessment and negative at the final assessment. |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Baseline and Day 1 of Cycles 2 to 75 (each cycle of 21 days) | SBP and DBP were obtained on Day 1 of each cycle. Baseline is the last assessment prior to first dose. Change from Baseline is the value at indicated time point minus the value at Baseline. NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time point. |
| Change From Baseline in Heart Rate | Baseline and Day 1 of Cycles 2 to 75 (each cycle of 21 days) | Heart rate was obtained on Day 1 of each cycle. Baseline is the last assessment prior to first dose. Change from Baseline is the value at indicated time point minus the value at Baseline. NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time point. |
| Change From Baseline in Temperature | Baseline and Day 1 of Cycles 2 to 75 (each cycle of 21 days) | Temperature was obtained on Day 1 of each cycle. Baseline is the last assessment prior to first dose. Change from Baseline is the value at indicated time point minus the value at Baseline. NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time point. |
| Change From Baseline in Respiratory Rate | Baseline and Day 1 of Cycles 2 to 75 (each cycle of 21 days) | Respiratory rate was obtained on Day 1 of each cycle. Baseline is the last assessment prior to first dose.Change from Baseline is the value at indicated time point minus the value at Baseline. NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time point. |
| Change From Baseline in Weight | Baseline and Day 1 of Cycles 2 to 75 (each cycle of 21 days) | Weight was obtained on Day 1 of each cycle. Baseline is the last assessment prior to first dose. Change from Baseline is the value at indicated time point minus the value at Baseline. NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time point. |
| Serum Concentration of Mapatumumab | Day1 pre-dose(Cycle 1,2,4,5,6,8,9,10,12,14,16,17,18,20,22,24,26,28,30,32,34);end of infusion (Cycle 1);Day8 pre-dose(Cycle 1);Day15 pre-dose (Cycle 1,2);Day21(Cycle 2,4,6,8,9,12,14,16,18,20,22,24,26,28,30,32,34);Cycle 99(end of treatment) (21-day cycles) | Blood samples were collected for determination of serum mapatumumab concentration at the indicated time points. NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time points. |
| Number of Participants With Severe AEs | Start of study treatment to maximum of 52.9 months | An AE is any unfavorable or unintended sign, symptom, or disease that is temporally associated with the use of a study agent but is not necessarily caused by the study agent. Severity of AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0. Grade 1 represents mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 represents moderate; minimal, local or non-invasive intervention indicated. Grade 3 represents severe or medically significant but not immediately life -threatening; hospitalization or prolongation of hospitalization indicated; disabling. Grade 4 represents life -threatening consequences; urgent intervention indicated. Grade 5 represents death related to AE. Severe AE is defined as AEs classified by investigator as severe (causing inability to carry out usual activities), life threatening or fatal using NCI-CTCAE Version 4.0 grading. |
Countries
Germany, Poland, Puerto Rico, Romania, Russia, Ukraine, United States
Participant flow
Recruitment details
This was a Phase 2, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of mapatumumab in combination with sorafenib in participants with advanced hepatocellular carcinoma.
Pre-assignment details
A total of 217 participants were screened of which 116 were screen failures and 101 participants were randomized in a ratio of 1:1 to any one of the 2 treatment arms. The study was conducted at 29 centers in 6 countries.
Participants by arm
| Arm | Count |
|---|---|
| Sorafenib+Placebo Participants received sorafenib 400 milligrams (mg) orally twice daily continuously in each 21-day cycle. Placebo was administered via the intravenous route on Day 1 of each 21-day cycle. The treatments were administered until radiologic disease progression or unacceptable toxicity | 51 |
| Sorafenib+Mapatumumab 30 mg/kg Participants received sorafenib 400 mg orally twice daily continuously in each 21-day cycle. Mapatumumab 30 milligrams per kilogram (mg/kg) was administered via the intravenous route on Day 1 of each 21-day cycle. The treatments were administered until radiologic disease progression or unacceptable toxicity | 50 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 10 |
| Overall Study | Clinical progression | 1 | 0 |
| Overall Study | Lack of compliance | 1 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Metastatic Hepatocellular Carcinoma | 1 | 0 |
| Overall Study | Physician Decision | 6 | 1 |
| Overall Study | Sponsor decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 5 |
Baseline characteristics
| Characteristic | Sorafenib+Mapatumumab 30 mg/kg | Total | Sorafenib+Placebo |
|---|---|---|---|
| Age, Continuous | 60.0 Years STANDARD_DEVIATION 11.93 | 60.4 Years STANDARD_DEVIATION 12.62 | 60.8 Years STANDARD_DEVIATION 13.36 |
| Race/Ethnicity, Customized Asian-East Asian Heritage | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized White/Caucasian - European Heritage | 48 Participants | 96 Participants | 48 Participants |
| Sex: Female, Male Female | 24 Participants | 36 Participants | 12 Participants |
| Sex: Female, Male Male | 26 Participants | 65 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 40 / 51 | 39 / 50 |
| other Total, other adverse events | 47 / 51 | 49 / 50 |
| serious Total, serious adverse events | 27 / 51 | 21 / 50 |
Outcome results
Primary
Time to Progression-Blinded Independent Central Review (BICR) Assessment
Time to progression is defined as the time from randomization to radiologic disease progression based on blinded independent review (BICR) of imaging scans using modified Response Evaluation Criteria in Solid Tumors assessment (mRECIST) for hepatocellular carcinoma. The primary analysis was performed using Kaplan Meier methods. The median time to progression is reported with one-sided 90% confidence interval. Analysis was performed on the modified Intent to Treat (mITT) Population which comprised of all randomized participants who received at least part of 1 dose of study agent (mapatumumab/placebo and/or sorafenib) with participants analyzed according to the groups to which they were randomized. NA indicates upper limit was not measurable as one-sided confidence interval is presented.
Time frame: Randomization to maximum of 24.1 months
Population: mITT Population. Only those participants who had their BICR scans read were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib+Placebo | Time to Progression-Blinded Independent Central Review (BICR) Assessment | 5.6 Months |
| Sorafenib+Mapatumumab 30 mg/kg | Time to Progression-Blinded Independent Central Review (BICR) Assessment | 4.1 Months |
p-value: 0.7382Stratified log-rank test
Secondary
Change From Baseline in Heart Rate
Heart rate was obtained on Day 1 of each cycle. Baseline is the last assessment prior to first dose. Change from Baseline is the value at indicated time point minus the value at Baseline. NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time point.
Time frame: Baseline and Day 1 of Cycles 2 to 75 (each cycle of 21 days)
Population: As Treated Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 23 DAY 1; n=4, 8 | -3.8 Beats per minute | Standard Deviation 6.02 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 12 DAY 1; n=15, 13 | -0.7 Beats per minute | Standard Deviation 4.28 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 24 DAY 1; n=4, 8 | -2.5 Beats per minute | Standard Deviation 5.97 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 7 DAY 1; n=24, 22 | 2.0 Beats per minute | Standard Deviation 8.4 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 25 DAY 1; n=4, 8 | -1.8 Beats per minute | Standard Deviation 2.06 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 13 DAY 1; n=13, 12 | 0.9 Beats per minute | Standard Deviation 5.47 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 26 DAY 1; n=4, 7 | -0.5 Beats per minute | Standard Deviation 1.91 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 3 DAY 1, n=39, 35 | 1.7 Beats per minute | Standard Deviation 7.69 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 27 DAY 1; n=4, 5 | -2.0 Beats per minute | Standard Deviation 2.31 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 14 DAY 1; n=12, 12 | 1.6 Beats per minute | Standard Deviation 7.03 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 28 DAY 1; n=4, 5 | -1.8 Beats per minute | Standard Deviation 5.56 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 8 DAY 1; n=22, 21 | 0.5 Beats per minute | Standard Deviation 7.7 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 29 DAY 1; n=3, 4 | 0.0 Beats per minute | Standard Deviation 4 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 15 DAY 1; n=10, 9 | 5.6 Beats per minute | Standard Deviation 12.39 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 30 DAY 1; n=3, 4 | 0.3 Beats per minute | Standard Deviation 2.08 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 5 DAY 1; n=27, 26 | 1.3 Beats per minute | Standard Deviation 9.45 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 31 DAY 1; n=3, 4 | -2.7 Beats per minute | Standard Deviation 6.43 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 17 DAY 1; n=8, 8 | 3.1 Beats per minute | Standard Deviation 7.2 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 32 DAY 1; n=3, 4 | 2.0 Beats per minute | Standard Deviation 4 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 9 DAY 1; n=19, 16 | 2.1 Beats per minute | Standard Deviation 8.04 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 33 DAY 1; n=2, 4 | -2.0 Beats per minute | Standard Deviation 0 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 18 DAY 1; n=8, 8 | 6.4 Beats per minute | Standard Deviation 8.68 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 34 DAY 1; n=1, 4 | 0.0 Beats per minute | — |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | Cycle 2 Day 1, n=46, 44 | 0.7 Beats per minute | Standard Deviation 8.32 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 19 DAY 1; n=6, 8 | -2.5 Beats per minute | Standard Deviation 10.54 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 10 DAY 1; n=18, 16 | 2.3 Beats per minute | Standard Deviation 8.62 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 20 DAY 1; n=6, 8 | 0.3 Beats per minute | Standard Deviation 6.38 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 6 DAY 1; n=24, 22 | 0.2 Beats per minute | Standard Deviation 10.37 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 21 DAY 1; n=4, 8 | 0.5 Beats per minute | Standard Deviation 1.91 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 11 DAY 1; n=16, 15 | -0.8 Beats per minute | Standard Deviation 6.51 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 22 DAY 1; n=4, 8 | 0.5 Beats per minute | Standard Deviation 1.91 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 4; DAY 1; n=33, 32 | 1.0 Beats per minute | Standard Deviation 10.09 |
| Sorafenib+Placebo | Change From Baseline in Heart Rate | CYCLE 16 DAY 1; n=10, 9 | 3.3 Beats per minute | Standard Deviation 7.06 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 34 DAY 1; n=1, 4 | -3.5 Beats per minute | Standard Deviation 4.43 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 35 DAY 1; n=0, 4 | -4.8 Beats per minute | Standard Deviation 4.99 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 36 DAY 1; n=0, 4 | -8.0 Beats per minute | Standard Deviation 8.37 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 37 DAY 1; n=0, 3 | -9.3 Beats per minute | Standard Deviation 6.11 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 38 DAY 1; n=0, 3 | -2.0 Beats per minute | Standard Deviation 6.93 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 39 DAY 1; n=0, 3 | -4.7 Beats per minute | Standard Deviation 6.43 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 40 DAY 1; n=0, 2 | -4.0 Beats per minute | Standard Deviation 8.49 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 41 DAY 1; n=0, 2 | -7.0 Beats per minute | Standard Deviation 9.9 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 42 DAY 1; n=0, 2 | -2.0 Beats per minute | Standard Deviation 8.49 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 43 DAY 1; n=0, 2 | -6.0 Beats per minute | Standard Deviation 14.14 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 44 DAY 1; n=0, 2 | -2.0 Beats per minute | Standard Deviation 14.14 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 45 DAY 1; n=0, 2 | -4.0 Beats per minute | Standard Deviation 14.14 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 46 DAY 1; n=0, 2 | -3.0 Beats per minute | Standard Deviation 18.38 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 47 DAY 1; n=0, 2 | -2.0 Beats per minute | Standard Deviation 14.14 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 48 DAY 1; n=0, 2 | -3.0 Beats per minute | Standard Deviation 15.56 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 49 DAY 1; n=0, 2 | -9.0 Beats per minute | Standard Deviation 9.9 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 50 DAY 1; n=0, 2 | -5.0 Beats per minute | Standard Deviation 9.9 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 51 DAY 1; n=0, 2 | -5.0 Beats per minute | Standard Deviation 12.73 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 52 DAY 1; n=0, 2 | -8.0 Beats per minute | Standard Deviation 11.31 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 53 DAY 1; n=0, 2 | -10.0 Beats per minute | Standard Deviation 2.83 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 54 DAY 1; n=0, 2 | -2.0 Beats per minute | Standard Deviation 8.49 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 55 DAY 1; n=0, 1 | -10.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 56 DAY 1; n=0, 1 | -12.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 57 DAY 1; n=0, 1 | -10.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 58 DAY 1; n=0, 1 | -8.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 59 DAY 1; n=0, 1 | -12.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 60 DAY 1; n=0, 1 | -10.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 61 DAY 1; n=0, 1 | -12.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 62 DAY 1; n=0, 1 | -14.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 63 DAY 1; n=0, 1 | -15.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 64 DAY 1; n=0, 1 | -10.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 65 DAY 1; n=0, 1 | -11.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 66 DAY 1; n=0, 1 | -12.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 67 DAY 1; n=0, 1 | -9.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 68 DAY 1; n=0, 1 | -10.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 69 DAY 1; n=0, 1 | -12.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 70 DAY 1; n=0, 1 | -9.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 71 DAY 1; n=0, 1 | -7.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 72 DAY 1; n=0, 1 | -10.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 73 DAY 1; n=0, 1 | -9.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 74 DAY 1; n=0, 1 | -8.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 75 DAY 1; n=0, 1 | -9.0 Beats per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 16 DAY 1; n=10, 9 | 0.7 Beats per minute | Standard Deviation 9.12 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | Cycle 2 Day 1, n=46, 44 | -1.8 Beats per minute | Standard Deviation 9.42 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 3 DAY 1, n=39, 35 | -1.6 Beats per minute | Standard Deviation 6.78 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 4; DAY 1; n=33, 32 | 1.9 Beats per minute | Standard Deviation 7.61 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 5 DAY 1; n=27, 26 | 0.2 Beats per minute | Standard Deviation 10.65 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 6 DAY 1; n=24, 22 | 0.3 Beats per minute | Standard Deviation 8.31 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 7 DAY 1; n=24, 22 | -1.8 Beats per minute | Standard Deviation 8.8 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 8 DAY 1; n=22, 21 | -0.4 Beats per minute | Standard Deviation 7.3 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 9 DAY 1; n=19, 16 | 0.3 Beats per minute | Standard Deviation 7.1 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 10 DAY 1; n=18, 16 | 0.5 Beats per minute | Standard Deviation 13.54 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 11 DAY 1; n=16, 15 | -2.0 Beats per minute | Standard Deviation 9.88 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 12 DAY 1; n=15, 13 | 0.2 Beats per minute | Standard Deviation 9.92 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 13 DAY 1; n=13, 12 | 0.9 Beats per minute | Standard Deviation 9.77 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 14 DAY 1; n=12, 12 | 3.1 Beats per minute | Standard Deviation 10.25 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 15 DAY 1; n=10, 9 | 2.2 Beats per minute | Standard Deviation 8.51 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 17 DAY 1; n=8, 8 | 1.6 Beats per minute | Standard Deviation 10.23 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 18 DAY 1; n=8, 8 | -0.5 Beats per minute | Standard Deviation 6.12 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 19 DAY 1; n=6, 8 | 0.5 Beats per minute | Standard Deviation 9.78 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 20 DAY 1; n=6, 8 | 0.9 Beats per minute | Standard Deviation 7.36 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 21 DAY 1; n=4, 8 | -1.4 Beats per minute | Standard Deviation 10.28 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 22 DAY 1; n=4, 8 | 3.0 Beats per minute | Standard Deviation 13.41 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 23 DAY 1; n=4, 8 | 2.9 Beats per minute | Standard Deviation 9.76 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 24 DAY 1; n=4, 8 | 2.9 Beats per minute | Standard Deviation 10.92 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 25 DAY 1; n=4, 8 | 0.3 Beats per minute | Standard Deviation 11.13 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 26 DAY 1; n=4, 7 | 1.6 Beats per minute | Standard Deviation 11.43 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 27 DAY 1; n=4, 5 | 2.4 Beats per minute | Standard Deviation 11.7 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 28 DAY 1; n=4, 5 | -0.2 Beats per minute | Standard Deviation 13.68 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 29 DAY 1; n=3, 4 | -3.8 Beats per minute | Standard Deviation 6.45 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 30 DAY 1; n=3, 4 | -9.3 Beats per minute | Standard Deviation 5.25 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 31 DAY 1; n=3, 4 | -0.8 Beats per minute | Standard Deviation 8.77 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 32 DAY 1; n=3, 4 | -3.8 Beats per minute | Standard Deviation 6.65 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Heart Rate | CYCLE 33 DAY 1; n=2, 4 | -5.5 Beats per minute | Standard Deviation 7.55 |
Secondary
Change From Baseline in Respiratory Rate
Respiratory rate was obtained on Day 1 of each cycle. Baseline is the last assessment prior to first dose.Change from Baseline is the value at indicated time point minus the value at Baseline. NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time point.
Time frame: Baseline and Day 1 of Cycles 2 to 75 (each cycle of 21 days)
Population: As Treated Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 23 DAY 1; n=4, 8 | 0.5 Breaths per minute | Standard Deviation 1 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 13 DAY 1; n=13, 12 | -0.2 Breaths per minute | Standard Deviation 1.69 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 24 DAY 1; n=4, 8 | -0.3 Breaths per minute | Standard Deviation 1.26 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 8 DAY 1; n=21, 21 | 0.6 Breaths per minute | Standard Deviation 1.78 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 25 DAY 1; n=4, 8 | -0.3 Breaths per minute | Standard Deviation 0.5 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 14 DAY 1; n=12, 12 | 0.4 Breaths per minute | Standard Deviation 2.43 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 26 DAY 1; n=4, 7 | -0.5 Breaths per minute | Standard Deviation 1 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 4; DAY 1; n=32, 32 | 0.2 Breaths per minute | Standard Deviation 1.79 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 27 DAY 1; n=4, 5 | 0.0 Breaths per minute | Standard Deviation 1.41 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 15 DAY 1; n=10, 9 | -0.5 Breaths per minute | Standard Deviation 1.65 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 28 DAY 1; n=4, 5 | -0.3 Breaths per minute | Standard Deviation 0.5 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 9 DAY 1; n=19, 16 | -0.5 Breaths per minute | Standard Deviation 1.98 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 29 DAY 1; n=3, 4 | -0.7 Breaths per minute | Standard Deviation 1.53 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 16 DAY 1; n=10, 9 | -0.5 Breaths per minute | Standard Deviation 1.72 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 30 DAY 1; n=3, 4 | 0.0 Breaths per minute | Standard Deviation 0 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 6 DAY 1; n=24, 22 | 0.5 Breaths per minute | Standard Deviation 2.15 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 31 DAY 1; n=3, 4 | 0.7 Breaths per minute | Standard Deviation 0.58 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 17 DAY 1; n=8, 8 | 0.0 Breaths per minute | Standard Deviation 2.2 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 32 DAY 1; n=3, 4 | -0.7 Breaths per minute | Standard Deviation 1.53 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 10 DAY 1; n=18, 16 | -1.7 Breaths per minute | Standard Deviation 2.95 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 33 DAY 1; n=2, 4 | -2.0 Breaths per minute | Standard Deviation 0 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 18 DAY 1; n=8, 8 | -0.4 Breaths per minute | Standard Deviation 2.07 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 34 DAY 1; n=1, 4 | 0.0 Breaths per minute | — |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 3 DAY 1, n=39, 35 | 0.2 Breaths per minute | Standard Deviation 2.34 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 19 DAY 1; n=6, 8 | 0.7 Breaths per minute | Standard Deviation 1.37 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 11 DAY 1; n=16, 15 | -0.8 Breaths per minute | Standard Deviation 1.97 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 20 DAY 1; n=6, 8 | 0.2 Breaths per minute | Standard Deviation 0.75 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 7 DAY 1; n=24, 22 | -0.1 Breaths per minute | Standard Deviation 2.09 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 21 DAY 1; n=4, 8 | 0.8 Breaths per minute | Standard Deviation 0.96 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 12 DAY 1; n=15, 13 | 0.0 Breaths per minute | Standard Deviation 2.48 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 22 DAY 1; n=4, 8 | 0.0 Breaths per minute | Standard Deviation 0 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 5 DAY 1; n=26, 26 | -0.1 Breaths per minute | Standard Deviation 1.86 |
| Sorafenib+Placebo | Change From Baseline in Respiratory Rate | CYCLE 2 Day 1, n=46, 44 | -0.1 Breaths per minute | Standard Deviation 1.62 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 34 DAY 1; n=1, 4 | 0.8 Breaths per minute | Standard Deviation 1.5 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 35 DAY 1; n=0, 4 | 0.0 Breaths per minute | Standard Deviation 1.83 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 36 DAY 1; n=0, 4 | 0.3 Breaths per minute | Standard Deviation 1.71 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 37 DAY 1; n=0, 3 | -1.0 Breaths per minute | Standard Deviation 1.73 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 38 DAY 1; n=0, 3 | -0.3 Breaths per minute | Standard Deviation 2.52 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 39 DAY 1; n=0, 3 | -1.0 Breaths per minute | Standard Deviation 1.73 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 40 DAY 1; n=0, 2 | 0.0 Breaths per minute | Standard Deviation 0 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 41 DAY 1; n=0, 2 | 0.0 Breaths per minute | Standard Deviation 0 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 42 DAY 1; n=0, 2 | 0.0 Breaths per minute | Standard Deviation 0 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 43 DAY 1; n=0, 2 | 0.0 Breaths per minute | Standard Deviation 0 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 44 DAY 1; n=0, 2 | 0.0 Breaths per minute | Standard Deviation 0 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 45 DAY 1; n=0, 2 | -1.5 Breaths per minute | Standard Deviation 0.71 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 46 DAY 1; n=0, 2 | 0.0 Breaths per minute | Standard Deviation 0 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 47 DAY 1; n=0, 2 | -0.5 Breaths per minute | Standard Deviation 0.71 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 48 DAY 1; n=0, 2 | 1.0 Breaths per minute | Standard Deviation 1.41 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 49 DAY 1; n=0, 2 | -1.0 Breaths per minute | Standard Deviation 1.41 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 50 DAY 1; n=0, 2 | 0.0 Breaths per minute | Standard Deviation 0 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 51 DAY 1; n=0, 2 | 0.0 Breaths per minute | Standard Deviation 0 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 52 DAY 1; n=0, 2 | 0.0 Breaths per minute | Standard Deviation 0 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 53 DAY 1; n=0, 2 | -1.0 Breaths per minute | Standard Deviation 1.41 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 54 DAY 1; n=0, 2 | 0.0 Breaths per minute | Standard Deviation 0 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 55 DAY 1; n=0, 1 | 0.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 56 DAY 1; n=0, 1 | 0.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 57 DAY 1; n=0, 1 | 0.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 58 DAY 1; n=0, 1 | 0.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 59 DAY 1; n=0, 1 | 0.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 60 DAY 1; n=0, 1 | 0.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 61 DAY 1; n=0, 1 | 0.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 62 DAY 1; n=0, 1 | -1.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 63 DAY 1; n=0, 1 | -1.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 64 DAY 1; n=0, 1 | -2.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 65 DAY 1; n=0, 1 | -2.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 66 DAY 1; n=0, 1 | -1.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 67 DAY 1; n=0, 1 | -2.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 68 DAY 1; n=0, 1 | -2.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 69 DAY 1; n=0, 1 | -1.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 70 DAY 1; n=0, 1 | -2.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 71 DAY 1; n=0, 1 | -2.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 72 DAY 1; n=0, 1 | -2.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 73 DAY 1; n=0, 1 | -2.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 74 DAY 1; n=0, 1 | -2.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 75 DAY 1; n=0, 1 | -2.0 Breaths per minute | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 2 Day 1, n=46, 44 | 0.1 Breaths per minute | Standard Deviation 1.31 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 3 DAY 1, n=39, 35 | -0.2 Breaths per minute | Standard Deviation 1.71 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 4; DAY 1; n=32, 32 | -0.3 Breaths per minute | Standard Deviation 1.45 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 5 DAY 1; n=26, 26 | -0.3 Breaths per minute | Standard Deviation 1.5 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 6 DAY 1; n=24, 22 | -0.3 Breaths per minute | Standard Deviation 1.88 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 7 DAY 1; n=24, 22 | -0.2 Breaths per minute | Standard Deviation 1.74 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 8 DAY 1; n=21, 21 | -0.1 Breaths per minute | Standard Deviation 1.59 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 9 DAY 1; n=19, 16 | -0.2 Breaths per minute | Standard Deviation 2.04 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 10 DAY 1; n=18, 16 | -0.4 Breaths per minute | Standard Deviation 2.03 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 11 DAY 1; n=16, 15 | -0.8 Breaths per minute | Standard Deviation 2.21 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 12 DAY 1; n=15, 13 | -1.0 Breaths per minute | Standard Deviation 2.45 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 13 DAY 1; n=13, 12 | -0.7 Breaths per minute | Standard Deviation 2.67 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 14 DAY 1; n=12, 12 | -1.0 Breaths per minute | Standard Deviation 2.52 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 15 DAY 1; n=10, 9 | -0.9 Breaths per minute | Standard Deviation 3.06 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 16 DAY 1; n=10, 9 | -0.9 Breaths per minute | Standard Deviation 2.76 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 17 DAY 1; n=8, 8 | 0.1 Breaths per minute | Standard Deviation 1.81 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 18 DAY 1; n=8, 8 | 0.4 Breaths per minute | Standard Deviation 1.6 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 19 DAY 1; n=6, 8 | 0.0 Breaths per minute | Standard Deviation 1.51 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 20 DAY 1; n=6, 8 | 0.0 Breaths per minute | Standard Deviation 1.6 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 21 DAY 1; n=4, 8 | -0.1 Breaths per minute | Standard Deviation 1.64 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 22 DAY 1; n=4, 8 | -0.1 Breaths per minute | Standard Deviation 1.36 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 23 DAY 1; n=4, 8 | 0.4 Breaths per minute | Standard Deviation 1.6 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 24 DAY 1; n=4, 8 | 0.0 Breaths per minute | Standard Deviation 1.2 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 25 DAY 1; n=4, 8 | -0.3 Breaths per minute | Standard Deviation 1.49 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 26 DAY 1; n=4, 7 | 0.0 Breaths per minute | Standard Deviation 1.63 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 27 DAY 1; n=4, 5 | 0.0 Breaths per minute | Standard Deviation 1 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 28 DAY 1; n=4, 5 | 0.2 Breaths per minute | Standard Deviation 2.17 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 29 DAY 1; n=3, 4 | -0.3 Breaths per minute | Standard Deviation 2.22 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 30 DAY 1; n=3, 4 | -0.3 Breaths per minute | Standard Deviation 2.06 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 31 DAY 1; n=3, 4 | 0.3 Breaths per minute | Standard Deviation 2.36 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 32 DAY 1; n=3, 4 | 0.0 Breaths per minute | Standard Deviation 2.16 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Respiratory Rate | CYCLE 33 DAY 1; n=2, 4 | -0.8 Breaths per minute | Standard Deviation 1.5 |
Secondary
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP and DBP were obtained on Day 1 of each cycle. Baseline is the last assessment prior to first dose. Change from Baseline is the value at indicated time point minus the value at Baseline. NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time point.
Time frame: Baseline and Day 1 of Cycles 2 to 75 (each cycle of 21 days)
Population: As Treated Population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 28 DAY 1; n=4, 5 | 3.3 Millimeters of mercury (mmHg) | Standard Deviation 7.41 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 3 DAY 1, n=39, 35 | 6.0 Millimeters of mercury (mmHg) | Standard Deviation 16.81 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 4; DAY 1; n=33, 32 | 2.1 Millimeters of mercury (mmHg) | Standard Deviation 15.57 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 5 DAY 1; n=27, 26 | 1.7 Millimeters of mercury (mmHg) | Standard Deviation 13.05 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 6 DAY 1; n=24, 22 | 1.3 Millimeters of mercury (mmHg) | Standard Deviation 12.14 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 7 DAY 1; n=24, 22 | -0.8 Millimeters of mercury (mmHg) | Standard Deviation 11.02 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 8 DAY 1; n=22, 21 | -1.6 Millimeters of mercury (mmHg) | Standard Deviation 11.48 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 9 DAY 1; n=19, 16 | 1.2 Millimeters of mercury (mmHg) | Standard Deviation 16.37 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 10 DAY 1; n=18, 16 | 1.4 Millimeters of mercury (mmHg) | Standard Deviation 16.57 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 11 DAY 1; n=16, 15 | 2.4 Millimeters of mercury (mmHg) | Standard Deviation 18.82 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 12 DAY 1; n=15, 13 | 2.7 Millimeters of mercury (mmHg) | Standard Deviation 12.34 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 13 DAY 1; n=13, 12 | 2.3 Millimeters of mercury (mmHg) | Standard Deviation 12.26 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 14 DAY 1; n=12, 12 | -1.0 Millimeters of mercury (mmHg) | Standard Deviation 10.13 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 15 DAY 1; n=10, 9 | 1.4 Millimeters of mercury (mmHg) | Standard Deviation 8.21 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 16 DAY 1; n=10, 9 | 1.8 Millimeters of mercury (mmHg) | Standard Deviation 5.79 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 17 DAY 1; n=8, 8 | 1.3 Millimeters of mercury (mmHg) | Standard Deviation 11.95 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 18 DAY 1; n=8, 8 | -2.0 Millimeters of mercury (mmHg) | Standard Deviation 9.26 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 19 DAY 1; n=6, 8 | -4.8 Millimeters of mercury (mmHg) | Standard Deviation 14.93 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 20 DAY 1; n=6, 8 | 1.2 Millimeters of mercury (mmHg) | Standard Deviation 9.13 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 21 DAY 1; n=4, 8 | 2.5 Millimeters of mercury (mmHg) | Standard Deviation 8.23 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 22 DAY 1; n=4, 8 | 6.0 Millimeters of mercury (mmHg) | Standard Deviation 10.55 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 23 DAY 1; n=4, 8 | -1.0 Millimeters of mercury (mmHg) | Standard Deviation 10.8 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 24 DAY 1; n=4, 8 | -3.0 Millimeters of mercury (mmHg) | Standard Deviation 6.38 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 25 DAY 1; n=4, 8 | 1.3 Millimeters of mercury (mmHg) | Standard Deviation 12.2 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 26 DAY 1; n=4, 7 | 6.0 Millimeters of mercury (mmHg) | Standard Deviation 11.89 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 27 DAY 1; n=4, 5 | 3.3 Millimeters of mercury (mmHg) | Standard Deviation 10.44 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; Cycle 2 Day 1, n=46, 44 | 2.3 Millimeters of mercury (mmHg) | Standard Deviation 14.13 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 29 DAY 1; n=3, 4 | -0.7 Millimeters of mercury (mmHg) | Standard Deviation 14.29 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 30 DAY 1; n=3, 4 | 2.7 Millimeters of mercury (mmHg) | Standard Deviation 6.43 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 31 DAY 1; n=3, 4 | -3.0 Millimeters of mercury (mmHg) | Standard Deviation 11.79 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 32 DAY 1; n=3, 4 | 5.0 Millimeters of mercury (mmHg) | Standard Deviation 4.58 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 33 DAY 1; n=2, 4 | 0.0 Millimeters of mercury (mmHg) | Standard Deviation 14.14 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 34 DAY 1; n=1, 4 | 13.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; Cycle 2 Day 1, n=46, 44 | -0.6 Millimeters of mercury (mmHg) | Standard Deviation 8.51 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 3 DAY 1, n=39, 35 | 2.1 Millimeters of mercury (mmHg) | Standard Deviation 7.2 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 4; DAY 1; n=33, 32 | 1.8 Millimeters of mercury (mmHg) | Standard Deviation 10.52 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 5 DAY 1; n=27, 26 | 0.9 Millimeters of mercury (mmHg) | Standard Deviation 10 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 6 DAY 1; n=24, 22 | 3.5 Millimeters of mercury (mmHg) | Standard Deviation 8.32 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 7 DAY 1; n=24, 22 | 0.5 Millimeters of mercury (mmHg) | Standard Deviation 8.57 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 8 DAY 1; n=22, 21 | 0.5 Millimeters of mercury (mmHg) | Standard Deviation 7.37 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 9 DAY 1; n=19, 16 | 2.7 Millimeters of mercury (mmHg) | Standard Deviation 8.67 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 10 DAY 1; n=18, 16 | 2.7 Millimeters of mercury (mmHg) | Standard Deviation 9.81 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 11 DAY 1; n=16, 15 | -0.1 Millimeters of mercury (mmHg) | Standard Deviation 10.25 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 12 DAY 1; n=15, 13 | 0.6 Millimeters of mercury (mmHg) | Standard Deviation 7.8 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 13 DAY 1; n=13, 12 | -2.2 Millimeters of mercury (mmHg) | Standard Deviation 6.07 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 14 DAY 1; n=12, 12 | 0.7 Millimeters of mercury (mmHg) | Standard Deviation 6.87 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 15 DAY 1; n=10, 9 | 2.1 Millimeters of mercury (mmHg) | Standard Deviation 8.49 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 16 DAY 1; n=10, 9 | 0.1 Millimeters of mercury (mmHg) | Standard Deviation 7.68 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 17 DAY 1; n=8, 8 | -1.5 Millimeters of mercury (mmHg) | Standard Deviation 8.23 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 18 DAY 1; n=8, 8 | 0.1 Millimeters of mercury (mmHg) | Standard Deviation 6.47 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 19 DAY 1; n=6, 8 | -2.5 Millimeters of mercury (mmHg) | Standard Deviation 5.82 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 20 DAY 1; n=6, 8 | 2.3 Millimeters of mercury (mmHg) | Standard Deviation 3.83 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 21 DAY 1; n=4, 8 | 0.8 Millimeters of mercury (mmHg) | Standard Deviation 2.99 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 22 DAY 1; n=4, 8 | -1.8 Millimeters of mercury (mmHg) | Standard Deviation 3.95 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 23 DAY 1; n=4, 8 | 2.5 Millimeters of mercury (mmHg) | Standard Deviation 4.2 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 24 DAY 1; n=4, 8 | -3.0 Millimeters of mercury (mmHg) | Standard Deviation 11.17 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 25 DAY 1; n=4, 8 | 3.5 Millimeters of mercury (mmHg) | Standard Deviation 3.11 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 26 DAY 1; n=4, 7 | 0.0 Millimeters of mercury (mmHg) | Standard Deviation 3.27 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 27 DAY 1; n=4, 5 | -3.3 Millimeters of mercury (mmHg) | Standard Deviation 4.72 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 28 DAY 1; n=4, 5 | 2.0 Millimeters of mercury (mmHg) | Standard Deviation 1.63 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 29 DAY 1; n=3, 4 | 1.7 Millimeters of mercury (mmHg) | Standard Deviation 10.41 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 30 DAY 1; n=3, 4 | -0.3 Millimeters of mercury (mmHg) | Standard Deviation 4.04 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 31 DAY 1; n=3, 4 | 6.7 Millimeters of mercury (mmHg) | Standard Deviation 7.64 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 32 DAY 1; n=3, 4 | 2.7 Millimeters of mercury (mmHg) | Standard Deviation 7.51 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 33 DAY 1; n=2, 4 | 0.5 Millimeters of mercury (mmHg) | Standard Deviation 7.78 |
| Sorafenib+Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 34 DAY 1; n=1, 4 | -15.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 35 DAY 1; n=0, 4 | -5.0 Millimeters of mercury (mmHg) | Standard Deviation 15.81 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 36 DAY 1; n=0, 4 | -1.5 Millimeters of mercury (mmHg) | Standard Deviation 13 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 37 DAY 1; n=0, 3 | -6.0 Millimeters of mercury (mmHg) | Standard Deviation 23.52 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 38 DAY 1; n=0, 3 | -1.3 Millimeters of mercury (mmHg) | Standard Deviation 18.04 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 39 DAY 1; n=0, 3 | -4.3 Millimeters of mercury (mmHg) | Standard Deviation 21.01 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 40 DAY 1; n=0, 2 | -12.5 Millimeters of mercury (mmHg) | Standard Deviation 10.61 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 41 DAY 1; n=0, 2 | -15.0 Millimeters of mercury (mmHg) | Standard Deviation 21.21 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 42 DAY 1; n=0, 2 | -7.5 Millimeters of mercury (mmHg) | Standard Deviation 17.68 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 43 DAY 1; n=0, 2 | -17.5 Millimeters of mercury (mmHg) | Standard Deviation 17.68 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 44 DAY 1; n=0, 2 | -10.0 Millimeters of mercury (mmHg) | Standard Deviation 14.14 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 45 DAY 1; n=0, 2 | -17.5 Millimeters of mercury (mmHg) | Standard Deviation 17.68 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 46 DAY 1; n=0, 2 | -5.0 Millimeters of mercury (mmHg) | Standard Deviation 21.21 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 47 DAY 1; n=0, 2 | -17.5 Millimeters of mercury (mmHg) | Standard Deviation 17.68 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 48 DAY 1; n=0, 2 | -5.0 Millimeters of mercury (mmHg) | Standard Deviation 21.21 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 49 DAY 1; n=0, 2 | -17.5 Millimeters of mercury (mmHg) | Standard Deviation 17.68 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 50 DAY 1; n=0, 2 | -15.0 Millimeters of mercury (mmHg) | Standard Deviation 21.21 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 51 DAY 1; n=0, 2 | -10.0 Millimeters of mercury (mmHg) | Standard Deviation 21.21 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 52 DAY 1; n=0, 2 | -17.5 Millimeters of mercury (mmHg) | Standard Deviation 17.68 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 53 DAY 1; n=0, 2 | -20.0 Millimeters of mercury (mmHg) | Standard Deviation 14.14 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 54 DAY 1; n=0, 2 | -10.0 Millimeters of mercury (mmHg) | Standard Deviation 14.14 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 55 DAY 1; n=0, 1 | -30.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 56 DAY 1; n=0, 1 | -30.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 57 DAY 1; n=0, 1 | -30.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 58 DAY 1; n=0, 1 | -25.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 59 DAY 1; n=0, 1 | -20.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 60 DAY 1; n=0, 1 | -30.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 61 DAY 1; n=0, 1 | -25.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 62 DAY 1; n=0, 1 | -23.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 63 DAY 1; n=0, 1 | -28.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 64 DAY 1; n=0, 1 | -25.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 65 DAY 1; n=0, 1 | -26.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 66 DAY 1; n=0, 1 | -32.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 67 DAY 1; n=0, 1 | -33.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 68 DAY 1; n=0, 1 | -32.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 69 DAY 1; n=0, 1 | -31.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 70 DAY 1; n=0, 1 | -25.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 71 DAY 1; n=0, 1 | -28.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 72 DAY 1; n=0, 1 | -30.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 73 DAY 1; n=0, 1 | -27.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 74 DAY 1; n=0, 1 | -30.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 75 DAY 1; n=0, 1 | -28.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 43 DAY 1; n=0, 2 | -7.5 Millimeters of mercury (mmHg) | Standard Deviation 3.54 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; Cycle 2 Day 1, n=46, 44 | 0.7 Millimeters of mercury (mmHg) | Standard Deviation 9.82 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 44 DAY 1; n=0, 2 | -2.5 Millimeters of mercury (mmHg) | Standard Deviation 3.54 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 3 DAY 1, n=39, 35 | 1.4 Millimeters of mercury (mmHg) | Standard Deviation 8.9 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 45 DAY 1; n=0, 2 | -7.5 Millimeters of mercury (mmHg) | Standard Deviation 3.54 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 4; DAY 1; n=33, 32 | 2.4 Millimeters of mercury (mmHg) | Standard Deviation 8.22 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 46 DAY 1; n=0, 2 | -5.0 Millimeters of mercury (mmHg) | Standard Deviation 7.07 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 5 DAY 1; n=27, 26 | 3.0 Millimeters of mercury (mmHg) | Standard Deviation 15.49 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 47 DAY 1; n=0, 2 | -3.0 Millimeters of mercury (mmHg) | Standard Deviation 24.04 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 6 DAY 1; n=24, 22 | 1.2 Millimeters of mercury (mmHg) | Standard Deviation 10.21 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 48 DAY 1; n=0, 2 | -5.0 Millimeters of mercury (mmHg) | Standard Deviation 7.07 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 7 DAY 1; n=24, 22 | 2.0 Millimeters of mercury (mmHg) | Standard Deviation 7.42 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 49 DAY 1; n=0, 2 | -12.5 Millimeters of mercury (mmHg) | Standard Deviation 3.54 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 8 DAY 1; n=22, 21 | 2.3 Millimeters of mercury (mmHg) | Standard Deviation 8.27 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 50 DAY 1; n=0, 2 | -5.0 Millimeters of mercury (mmHg) | Standard Deviation 7.07 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 9 DAY 1; n=19, 16 | 4.1 Millimeters of mercury (mmHg) | Standard Deviation 9.15 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 51 DAY 1; n=0, 2 | -5.0 Millimeters of mercury (mmHg) | Standard Deviation 7.07 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 10 DAY 1; n=18, 16 | 2.4 Millimeters of mercury (mmHg) | Standard Deviation 7.5 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 52 DAY 1; n=0, 2 | -10.0 Millimeters of mercury (mmHg) | Standard Deviation 7.07 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 11 DAY 1; n=16, 15 | 0.9 Millimeters of mercury (mmHg) | Standard Deviation 9.49 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 53 DAY 1; n=0, 2 | -7.5 Millimeters of mercury (mmHg) | Standard Deviation 3.54 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 12 DAY 1; n=15, 13 | 2.1 Millimeters of mercury (mmHg) | Standard Deviation 8.65 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 54 DAY 1; n=0, 2 | -5.0 Millimeters of mercury (mmHg) | Standard Deviation 7.07 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 13 DAY 1; n=13, 12 | -2.7 Millimeters of mercury (mmHg) | Standard Deviation 7.64 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 55 DAY 1; n=0, 1 | -15.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 14 DAY 1; n=12, 12 | 3.3 Millimeters of mercury (mmHg) | Standard Deviation 11.78 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 56 DAY 1; n=0, 1 | -10.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 15 DAY 1; n=10, 9 | 1.1 Millimeters of mercury (mmHg) | Standard Deviation 12.97 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 57 DAY 1; n=0, 1 | -15.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 16 DAY 1; n=10, 9 | 0.1 Millimeters of mercury (mmHg) | Standard Deviation 11.88 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 58 DAY 1; n=0, 1 | -10.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 17 DAY 1; n=8, 8 | 5.0 Millimeters of mercury (mmHg) | Standard Deviation 7.15 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 59 DAY 1; n=0, 1 | -10.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 18 DAY 1; n=8, 8 | 3.4 Millimeters of mercury (mmHg) | Standard Deviation 11.15 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 60 DAY 1; n=0, 1 | -15.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 19 DAY 1; n=6, 8 | 5.5 Millimeters of mercury (mmHg) | Standard Deviation 12.17 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 61 DAY 1; n=0, 1 | -15.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 20 DAY 1; n=6, 8 | 3.5 Millimeters of mercury (mmHg) | Standard Deviation 10.09 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 62 DAY 1; n=0, 1 | -13.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 21 DAY 1; n=4, 8 | 2.8 Millimeters of mercury (mmHg) | Standard Deviation 11.96 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 63 DAY 1; n=0, 1 | -15.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 22 DAY 1; n=4, 8 | 3.8 Millimeters of mercury (mmHg) | Standard Deviation 7.63 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; Cycle 2 Day 1, n=46, 44 | 2.2 Millimeters of mercury (mmHg) | Standard Deviation 18.64 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 64 DAY 1; n=0, 1 | -14.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 3 DAY 1, n=39, 35 | 4.1 Millimeters of mercury (mmHg) | Standard Deviation 13.66 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 23 DAY 1; n=4, 8 | 5.1 Millimeters of mercury (mmHg) | Standard Deviation 12.12 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 4; DAY 1; n=33, 32 | 5.3 Millimeters of mercury (mmHg) | Standard Deviation 13.52 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 65 DAY 1; n=0, 1 | -15.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 5 DAY 1; n=27, 26 | 4.9 Millimeters of mercury (mmHg) | Standard Deviation 16.42 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 24 DAY 1; n=4, 8 | 2.5 Millimeters of mercury (mmHg) | Standard Deviation 12.99 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 6 DAY 1; n=24, 22 | 5.1 Millimeters of mercury (mmHg) | Standard Deviation 13.4 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 66 DAY 1; n=0, 1 | -17.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 7 DAY 1; n=24, 22 | 5.0 Millimeters of mercury (mmHg) | Standard Deviation 12.78 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 25 DAY 1; n=4, 8 | 2.5 Millimeters of mercury (mmHg) | Standard Deviation 15.8 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 8 DAY 1; n=22, 21 | 5.2 Millimeters of mercury (mmHg) | Standard Deviation 14.83 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 67 DAY 1; n=0, 1 | -14.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 9 DAY 1; n=19, 16 | 7.8 Millimeters of mercury (mmHg) | Standard Deviation 13.98 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 26 DAY 1; n=4, 7 | 4.0 Millimeters of mercury (mmHg) | Standard Deviation 14.57 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 10 DAY 1; n=18, 16 | 4.5 Millimeters of mercury (mmHg) | Standard Deviation 16.19 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 68 DAY 1; n=0, 1 | -15.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 11 DAY 1; n=16, 15 | 5.2 Millimeters of mercury (mmHg) | Standard Deviation 18.32 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 27 DAY 1; n=4, 5 | 3.6 Millimeters of mercury (mmHg) | Standard Deviation 11.67 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 12 DAY 1; n=15, 13 | 5.2 Millimeters of mercury (mmHg) | Standard Deviation 14.73 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 69 DAY 1; n=0, 1 | -17.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 13 DAY 1; n=13, 12 | 3.0 Millimeters of mercury (mmHg) | Standard Deviation 14.91 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 28 DAY 1; n=4, 5 | 4.0 Millimeters of mercury (mmHg) | Standard Deviation 14.21 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 14 DAY 1; n=12, 12 | 4.0 Millimeters of mercury (mmHg) | Standard Deviation 14.63 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 70 DAY 1; n=0, 1 | -16.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 15 DAY 1; n=10, 9 | 6.7 Millimeters of mercury (mmHg) | Standard Deviation 21.05 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 29 DAY 1; n=3, 4 | -2.0 Millimeters of mercury (mmHg) | Standard Deviation 7.26 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 16 DAY 1; n=10, 9 | 7.9 Millimeters of mercury (mmHg) | Standard Deviation 15.28 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 71 DAY 1; n=0, 1 | -15.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 17 DAY 1; n=8, 8 | 10.1 Millimeters of mercury (mmHg) | Standard Deviation 17.7 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 30 DAY 1; n=3, 4 | -2.3 Millimeters of mercury (mmHg) | Standard Deviation 6.6 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 18 DAY 1; n=8, 8 | 9.5 Millimeters of mercury (mmHg) | Standard Deviation 19.41 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 72 DAY 1; n=0, 1 | -19.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 19 DAY 1; n=6, 8 | 8.4 Millimeters of mercury (mmHg) | Standard Deviation 20.68 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 31 DAY 1; n=3, 4 | 0.5 Millimeters of mercury (mmHg) | Standard Deviation 11.45 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 20 DAY 1; n=6, 8 | 5.8 Millimeters of mercury (mmHg) | Standard Deviation 19.33 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 73 DAY 1; n=0, 1 | -15.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 21 DAY 1; n=4, 8 | 10.0 Millimeters of mercury (mmHg) | Standard Deviation 21.23 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 32 DAY 1; n=3, 4 | -0.3 Millimeters of mercury (mmHg) | Standard Deviation 7.76 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 22 DAY 1; n=4, 8 | 5.5 Millimeters of mercury (mmHg) | Standard Deviation 14.11 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 74 DAY 1; n=0, 1 | -14.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 23 DAY 1; n=4, 8 | 12.9 Millimeters of mercury (mmHg) | Standard Deviation 20.15 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 33 DAY 1; n=2, 4 | -2.5 Millimeters of mercury (mmHg) | Standard Deviation 8.5 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 24 DAY 1; n=4, 8 | 5.6 Millimeters of mercury (mmHg) | Standard Deviation 19.86 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 75 DAY 1; n=0, 1 | -17.0 Millimeters of mercury (mmHg) | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 25 DAY 1; n=4, 8 | 11.3 Millimeters of mercury (mmHg) | Standard Deviation 20.08 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 34 DAY 1; n=1, 4 | -1.8 Millimeters of mercury (mmHg) | Standard Deviation 6.99 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 26 DAY 1; n=4, 7 | 9.3 Millimeters of mercury (mmHg) | Standard Deviation 22.92 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 35 DAY 1; n=0, 4 | -3.0 Millimeters of mercury (mmHg) | Standard Deviation 8.12 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 27 DAY 1; n=4, 5 | 8.4 Millimeters of mercury (mmHg) | Standard Deviation 18.04 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 36 DAY 1; n=0, 4 | 1.5 Millimeters of mercury (mmHg) | Standard Deviation 3 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 28 DAY 1; n=4, 5 | 5.2 Millimeters of mercury (mmHg) | Standard Deviation 20.19 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 37 DAY 1; n=0, 3 | 1.7 Millimeters of mercury (mmHg) | Standard Deviation 12.58 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 29 DAY 1; n=3, 4 | 3.3 Millimeters of mercury (mmHg) | Standard Deviation 24.27 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 38 DAY 1; n=0, 3 | -2.3 Millimeters of mercury (mmHg) | Standard Deviation 6.81 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 30 DAY 1; n=3, 4 | -2.3 Millimeters of mercury (mmHg) | Standard Deviation 13.43 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 39 DAY 1; n=0, 3 | 0.3 Millimeters of mercury (mmHg) | Standard Deviation 10.5 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 31 DAY 1; n=3, 4 | 2.0 Millimeters of mercury (mmHg) | Standard Deviation 23.15 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 40 DAY 1; n=0, 2 | 0.0 Millimeters of mercury (mmHg) | Standard Deviation 0 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 32 DAY 1; n=3, 4 | 3.3 Millimeters of mercury (mmHg) | Standard Deviation 16.4 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 41 DAY 1; n=0, 2 | -7.5 Millimeters of mercury (mmHg) | Standard Deviation 3.54 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 33 DAY 1; n=2, 4 | -5.3 Millimeters of mercury (mmHg) | Standard Deviation 19.96 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; CYCLE 42 DAY 1; n=0, 2 | 0.0 Millimeters of mercury (mmHg) | Standard Deviation 0 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; CYCLE 34 DAY 1; n=1, 4 | -5.3 Millimeters of mercury (mmHg) | Standard Deviation 10.66 |
Secondary
Change From Baseline in Temperature
Temperature was obtained on Day 1 of each cycle. Baseline is the last assessment prior to first dose. Change from Baseline is the value at indicated time point minus the value at Baseline. NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time point.
Time frame: Baseline and Day 1 of Cycles 2 to 75 (each cycle of 21 days)
Population: As Treated Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 23 DAY 1; n=4, 8 | 0.03 Celsius | Standard Deviation 0.299 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 13 DAY 1; n=13, 12 | 0.00 Celsius | Standard Deviation 0.354 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 24 DAY 1; n=4, 8 | 0.18 Celsius | Standard Deviation 0.171 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 8 DAY 1; n=21, 21 | 0.01 Celsius | Standard Deviation 0.46 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 25 DAY 1; n=4, 8 | 0.20 Celsius | Standard Deviation 0.432 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 14 DAY 1; n=12, 12 | 0.13 Celsius | Standard Deviation 0.38 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 26 DAY 1; n=4, 7 | 0.15 Celsius | Standard Deviation 0.129 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 4; DAY 1; n=33, 32 | 0.02 Celsius | Standard Deviation 0.354 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 27 DAY 1; n=4, 5 | 0.18 Celsius | Standard Deviation 0.171 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 15 DAY 1; n=10, 9 | 0.11 Celsius | Standard Deviation 0.42 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 28 DAY 1; n=4, 5 | 0.15 Celsius | Standard Deviation 0.208 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 9 DAY 1; n=19, 16 | 0.04 Celsius | Standard Deviation 0.493 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 29 DAY 1; n=3, 4 | 0.13 Celsius | Standard Deviation 0.153 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 16 DAY 1; n=10, 9 | 0.01 Celsius | Standard Deviation 0.318 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 30 DAY 1; n=3, 4 | 0.10 Celsius | Standard Deviation 0.173 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 6 DAY 1; n=23, 22 | -0.05 Celsius | Standard Deviation 0.374 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 31 DAY 1; n=3, 4 | -0.07 Celsius | Standard Deviation 0.351 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 17 DAY 1; n=8, 8 | 0.00 Celsius | Standard Deviation 0.227 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 32 DAY 1; n=3, 4 | 0.10 Celsius | Standard Deviation 0.173 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 10 DAY 1; n=18, 16 | 0.05 Celsius | Standard Deviation 0.539 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 33 DAY 1; n=2, 4 | 0.30 Celsius | Standard Deviation 0.424 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 18 DAY 1; n=8, 8 | -0.14 Celsius | Standard Deviation 0.346 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 34 DAY 1; n=1, 4 | 0.30 Celsius | — |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 3 DAY 1, n=39, 35 | -0.01 Celsius | Standard Deviation 0.374 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 19 DAY 1; n=6, 8 | -0.10 Celsius | Standard Deviation 0.456 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 11 DAY 1; n=16, 15 | -0.02 Celsius | Standard Deviation 0.468 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 20 DAY 1; n=6, 8 | -0.02 Celsius | Standard Deviation 0.397 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 7 DAY 1; n=24, 22 | 0.03 Celsius | Standard Deviation 0.334 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 21 DAY 1; n=4, 8 | 0.13 Celsius | Standard Deviation 0.411 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 12 DAY 1; n=15, 13 | 0.00 Celsius | Standard Deviation 0.27 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 22 DAY 1; n=4, 8 | 0.17 Celsius | Standard Deviation 0.206 |
| Sorafenib+Placebo | Change From Baseline in Temperature | CYCLE 5 DAY 1; n=27, 26 | 0.05 Celsius | Standard Deviation 0.374 |
| Sorafenib+Placebo | Change From Baseline in Temperature | Cycle 2 Day 1, n=46, 43 | 0.02 Celsius | Standard Deviation 0.288 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 34 DAY 1; n=1, 4 | -0.20 Celsius | Standard Deviation 0.283 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 35 DAY 1; n=0, 4 | -0.05 Celsius | Standard Deviation 0.058 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 36 DAY 1; n=0, 4 | -0.07 Celsius | Standard Deviation 0.15 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 37 DAY 1; n=0, 3 | -0.30 Celsius | Standard Deviation 0.458 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 38 DAY 1; n=0, 3 | 0.00 Celsius | Standard Deviation 0.1 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 39 DAY 1; n=0, 3 | -0.07 Celsius | Standard Deviation 0.058 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 40 DAY 1; n=0, 2 | 0.00 Celsius | Standard Deviation 0 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 41 DAY 1; n=0, 2 | -0.10 Celsius | Standard Deviation 0.141 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 42 DAY 1; n=0, 2 | 0.05 Celsius | Standard Deviation 0.071 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 43 DAY 1; n=0, 2 | -0.05 Celsius | Standard Deviation 0.212 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 44 DAY 1; n=0, 2 | 0.00 Celsius | Standard Deviation 0.141 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 45 DAY 1; n=0, 2 | 0.00 Celsius | Standard Deviation 0.283 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 46 DAY 1; n=0, 2 | -0.05 Celsius | Standard Deviation 0.071 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 47 DAY 1; n=0, 2 | 0.05 Celsius | Standard Deviation 0.212 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 48 DAY 1; n=0, 2 | 0.00 Celsius | Standard Deviation 0 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 49 DAY 1; n=0, 2 | -0.05 Celsius | Standard Deviation 0.212 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 50 DAY 1; n=0, 2 | 0.00 Celsius | Standard Deviation 0.141 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 51 DAY 1; n=0, 2 | -0.05 Celsius | Standard Deviation 0.071 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 52 DAY 1; n=0, 2 | -0.10 Celsius | Standard Deviation 0.141 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 53 DAY 1; n=0, 2 | 0.05 Celsius | Standard Deviation 0.071 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 54 DAY 1; n=0, 2 | -0.05 Celsius | Standard Deviation 0.071 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 55 DAY 1; n=0, 1 | -0.20 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 56 DAY 1; n=0, 1 | -0.10 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 57 DAY 1; n=0, 1 | 0.00 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 58 DAY 1; n=0, 1 | -0.10 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 59 DAY 1; n=0, 1 | 0.00 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 60 DAY 1; n=0, 1 | -0.10 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 61 DAY 1; n=0, 1 | -0.10 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 62 DAY 1; n=0, 1 | 0.00 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 63 DAY 1; n=0, 1 | -0.10 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 64 DAY 1; n=0, 1 | -0.10 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 65 DAY 1; n=0, 1 | 0.00 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 66 DAY 1; n=0, 1 | -0.20 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 67 DAY 1; n=0, 1 | -0.10 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 68 DAY 1; n=0, 1 | 0.00 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 69 DAY 1; n=0, 1 | -0.20 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 70 DAY 1; n=0, 1 | 0.00 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 71 DAY 1; n=0, 1 | -0.10 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 72 DAY 1; n=0, 1 | -0.20 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 73 DAY 1; n=0, 1 | -0.10 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 74 DAY 1; n=0, 1 | -0.20 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 75 DAY 1; n=0, 1 | -0.10 Celsius | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | Cycle 2 Day 1, n=46, 43 | -0.02 Celsius | Standard Deviation 0.242 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 3 DAY 1, n=39, 35 | -0.11 Celsius | Standard Deviation 0.34 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 4; DAY 1; n=33, 32 | -0.05 Celsius | Standard Deviation 0.298 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 5 DAY 1; n=27, 26 | -0.04 Celsius | Standard Deviation 0.218 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 6 DAY 1; n=23, 22 | -0.07 Celsius | Standard Deviation 0.223 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 7 DAY 1; n=24, 22 | -0.10 Celsius | Standard Deviation 0.408 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 8 DAY 1; n=21, 21 | 0.02 Celsius | Standard Deviation 0.161 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 9 DAY 1; n=19, 16 | 0.00 Celsius | Standard Deviation 0.171 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 10 DAY 1; n=18, 16 | 0.04 Celsius | Standard Deviation 0.2 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 11 DAY 1; n=16, 15 | -0.09 Celsius | Standard Deviation 0.181 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 12 DAY 1; n=15, 13 | 0.02 Celsius | Standard Deviation 0.245 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 13 DAY 1; n=13, 12 | 0.03 Celsius | Standard Deviation 0.176 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 14 DAY 1; n=12, 12 | -0.04 Celsius | Standard Deviation 0.219 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 15 DAY 1; n=10, 9 | -0.13 Celsius | Standard Deviation 0.269 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 16 DAY 1; n=10, 9 | -0.04 Celsius | Standard Deviation 0.174 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 17 DAY 1; n=8, 8 | 0.05 Celsius | Standard Deviation 0.076 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 18 DAY 1; n=8, 8 | -0.09 Celsius | Standard Deviation 0.189 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 19 DAY 1; n=6, 8 | 0.10 Celsius | Standard Deviation 0.207 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 20 DAY 1; n=6, 8 | 0.01 Celsius | Standard Deviation 0.146 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 21 DAY 1; n=4, 8 | -0.01 Celsius | Standard Deviation 0.304 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 22 DAY 1; n=4, 8 | 0.00 Celsius | Standard Deviation 0.193 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 23 DAY 1; n=4, 8 | 0.13 Celsius | Standard Deviation 0.231 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 24 DAY 1; n=4, 8 | 0.06 Celsius | Standard Deviation 0.119 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 25 DAY 1; n=4, 8 | 0.00 Celsius | Standard Deviation 0.185 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 26 DAY 1; n=4, 7 | -0.01 Celsius | Standard Deviation 0.308 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 27 DAY 1; n=4, 5 | 0.10 Celsius | Standard Deviation 0.173 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 28 DAY 1; n=4, 5 | -0.02 Celsius | Standard Deviation 0.179 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 29 DAY 1; n=3, 4 | -0.02 Celsius | Standard Deviation 0.275 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 30 DAY 1; n=3, 4 | 0.00 Celsius | Standard Deviation 0.082 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 31 DAY 1; n=3, 4 | 0.05 Celsius | Standard Deviation 0.265 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 32 DAY 1; n=3, 4 | -0.05 Celsius | Standard Deviation 0.265 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Temperature | CYCLE 33 DAY 1; n=2, 4 | -0.07 Celsius | Standard Deviation 0.222 |
Secondary
Change From Baseline in Weight
Weight was obtained on Day 1 of each cycle. Baseline is the last assessment prior to first dose. Change from Baseline is the value at indicated time point minus the value at Baseline. NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time point.
Time frame: Baseline and Day 1 of Cycles 2 to 75 (each cycle of 21 days)
Population: As Treated Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 23 DAY 1; n=4, 8 | -4.13 Kilograms | Standard Deviation 8.189 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 13 DAY 1; n=13, 12 | -6.54 Kilograms | Standard Deviation 5.795 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 24 DAY 1; n=4, 7 | -3.38 Kilograms | Standard Deviation 7.273 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 8 DAY 1; n=22, 21 | -3.89 Kilograms | Standard Deviation 4.384 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 25 DAY 1; n=4, 8 | -3.88 Kilograms | Standard Deviation 8.25 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 14 DAY 1; n=12, 12 | -7.03 Kilograms | Standard Deviation 6.5 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 26 DAY 1; n=4, 7 | -3.88 Kilograms | Standard Deviation 6.981 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 4; DAY 1; n=33, 32 | -3.02 Kilograms | Standard Deviation 2.451 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 27 DAY 1; n=4, 5 | -4.88 Kilograms | Standard Deviation 6.408 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 15 DAY 1; n=10, 9 | -7.21 Kilograms | Standard Deviation 7.449 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 28 DAY 1; n=4, 5 | -5.13 Kilograms | Standard Deviation 6.115 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 9 DAY 1; n=19, 16 | -4.14 Kilograms | Standard Deviation 5.151 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 29 DAY 1; n=3, 4 | -5.50 Kilograms | Standard Deviation 7.697 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 16 DAY 1; n=10, 9 | -7.59 Kilograms | Standard Deviation 6.97 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 30 DAY 1; n=3, 4 | -5.83 Kilograms | Standard Deviation 7.286 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 6 DAY 1; n=24, 22 | -3.25 Kilograms | Standard Deviation 3.078 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 31 DAY 1; n=3, 4 | -5.50 Kilograms | Standard Deviation 7.467 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 17 DAY 1; n=8, 8 | -8.49 Kilograms | Standard Deviation 8.606 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 32 DAY 1; n=3, 4 | -5.50 Kilograms | Standard Deviation 7.467 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 10 DAY 1; n=18, 16 | -5.50 Kilograms | Standard Deviation 6.983 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 33 DAY 1; n=2, 4 | -1.75 Kilograms | Standard Deviation 1.061 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 18 DAY 1; n=8, 8 | -8.25 Kilograms | Standard Deviation 9.002 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 34 DAY 1; n=1, 4 | -2.50 Kilograms | — |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 3 DAY 1, n=39, 35 | -2.54 Kilograms | Standard Deviation 2.734 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 19 DAY 1; n=6, 8 | -8.78 Kilograms | Standard Deviation 9.953 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 11 DAY 1; n=16, 15 | -5.70 Kilograms | Standard Deviation 6.045 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 20 DAY 1; n=6, 8 | -9.22 Kilograms | Standard Deviation 10.752 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 7 DAY 1; n=24, 22 | -3.75 Kilograms | Standard Deviation 4.172 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 21 DAY 1; n=4, 8 | -3.03 Kilograms | Standard Deviation 7.95 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 12 DAY 1; n=15, 13 | -5.85 Kilograms | Standard Deviation 5.206 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 22 DAY 1; n=4, 8 | -3.50 Kilograms | Standard Deviation 7.735 |
| Sorafenib+Placebo | Change From Baseline in Weight | CYCLE 5 DAY 1; n=27, 26 | -3.31 Kilograms | Standard Deviation 2.521 |
| Sorafenib+Placebo | Change From Baseline in Weight | Cycle 2 Day 1, n=46, 44 | -1.51 Kilograms | Standard Deviation 2.192 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 34 DAY 1; n=1, 4 | -3.18 Kilograms | Standard Deviation 0.35 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 35 DAY 1; n=0, 4 | -3.25 Kilograms | Standard Deviation 0.379 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 36 DAY 1; n=0, 4 | -3.38 Kilograms | Standard Deviation 0.624 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 37 DAY 1; n=0, 3 | -3.17 Kilograms | Standard Deviation 0.961 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 38 DAY 1; n=0, 3 | -2.63 Kilograms | Standard Deviation 0.814 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 39 DAY 1; n=0, 3 | -3.00 Kilograms | Standard Deviation 0.2 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 40 DAY 1; n=0, 2 | -3.40 Kilograms | Standard Deviation 0.566 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 41 DAY 1; n=0, 2 | -2.90 Kilograms | Standard Deviation 0.141 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 42 DAY 1; n=0, 2 | -3.00 Kilograms | Standard Deviation 0 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 43 DAY 1; n=0, 2 | -2.90 Kilograms | Standard Deviation 0.141 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 44 DAY 1; n=0, 2 | -3.90 Kilograms | Standard Deviation 1.273 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 45 DAY 1; n=0, 2 | -4.40 Kilograms | Standard Deviation 1.98 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 46 DAY 1; n=0, 2 | -3.90 Kilograms | Standard Deviation 1.273 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 47 DAY 1; n=0, 2 | -3.40 Kilograms | Standard Deviation 0.566 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 48 DAY 1; n=0, 2 | -3.65 Kilograms | Standard Deviation 0.919 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 49 DAY 1; n=0, 2 | -4.40 Kilograms | Standard Deviation 1.98 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 50 DAY 1; n=0, 2 | -4.15 Kilograms | Standard Deviation 1.626 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 51 DAY 1; n=0, 2 | -3.65 Kilograms | Standard Deviation 0.919 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 52 DAY 1; n=0, 2 | -2.90 Kilograms | Standard Deviation 0.141 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 53 DAY 1; n=0, 2 | -4.40 Kilograms | Standard Deviation 1.98 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 54 DAY 1; n=0, 2 | -3.65 Kilograms | Standard Deviation 0.919 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 55 DAY 1; n=0, 1 | -2.80 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 56 DAY 1; n=0, 1 | -1.80 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 57 DAY 1; n=0, 1 | -0.80 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 58 DAY 1; n=0, 1 | -1.30 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 59 DAY 1; n=0, 1 | -0.30 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 60 DAY 1; n=0, 1 | -0.30 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 61 DAY 1; n=0, 1 | 0.00 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 62 DAY 1; n=0, 1 | -0.30 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 63 DAY 1; n=0, 1 | -0.80 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 64 DAY 1; n=0, 1 | -0.60 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 65 DAY 1; n=0, 1 | -2.80 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 66 DAY 1; n=0, 1 | -3.30 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 67 DAY 1; n=0, 1 | -3.80 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 68 DAY 1; n=0, 1 | -1.30 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 69 DAY 1; n=0, 1 | -1.80 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 70 DAY 1; n=0, 1 | 0.20 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 71 DAY 1; n=0, 1 | -0.80 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 72 DAY 1; n=0, 1 | -0.80 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 73 DAY 1; n=0, 1 | -1.30 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 74 DAY 1; n=0, 1 | -0.80 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 75 DAY 1; n=0, 1 | -0.30 Kilograms | — |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | Cycle 2 Day 1, n=46, 44 | -1.55 Kilograms | Standard Deviation 2.405 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 3 DAY 1, n=39, 35 | -1.88 Kilograms | Standard Deviation 2.71 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 4; DAY 1; n=33, 32 | -1.86 Kilograms | Standard Deviation 3.305 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 5 DAY 1; n=27, 26 | -2.01 Kilograms | Standard Deviation 3.301 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 6 DAY 1; n=24, 22 | -2.61 Kilograms | Standard Deviation 4.2 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 7 DAY 1; n=24, 22 | -2.14 Kilograms | Standard Deviation 5.877 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 8 DAY 1; n=22, 21 | -2.61 Kilograms | Standard Deviation 5.016 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 9 DAY 1; n=19, 16 | -2.14 Kilograms | Standard Deviation 4.998 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 10 DAY 1; n=18, 16 | -1.99 Kilograms | Standard Deviation 5.478 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 11 DAY 1; n=16, 15 | -1.67 Kilograms | Standard Deviation 4.681 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 12 DAY 1; n=15, 13 | -1.72 Kilograms | Standard Deviation 4.26 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 13 DAY 1; n=13, 12 | -1.11 Kilograms | Standard Deviation 4.483 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 14 DAY 1; n=12, 12 | -1.23 Kilograms | Standard Deviation 3.899 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 15 DAY 1; n=10, 9 | -1.09 Kilograms | Standard Deviation 4.705 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 16 DAY 1; n=10, 9 | -0.93 Kilograms | Standard Deviation 4.519 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 17 DAY 1; n=8, 8 | -1.24 Kilograms | Standard Deviation 5.205 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 18 DAY 1; n=8, 8 | -0.80 Kilograms | Standard Deviation 4.888 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 19 DAY 1; n=6, 8 | -0.19 Kilograms | Standard Deviation 5.044 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 20 DAY 1; n=6, 8 | -0.40 Kilograms | Standard Deviation 5.986 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 21 DAY 1; n=4, 8 | -0.29 Kilograms | Standard Deviation 6.354 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 22 DAY 1; n=4, 8 | -0.32 Kilograms | Standard Deviation 5.37 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 23 DAY 1; n=4, 8 | -0.16 Kilograms | Standard Deviation 5.297 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 24 DAY 1; n=4, 7 | -1.93 Kilograms | Standard Deviation 1.511 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 25 DAY 1; n=4, 8 | 0.04 Kilograms | Standard Deviation 5.789 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 26 DAY 1; n=4, 7 | 0.54 Kilograms | Standard Deviation 6.484 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 27 DAY 1; n=4, 5 | -2.04 Kilograms | Standard Deviation 2.308 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 28 DAY 1; n=4, 5 | -2.20 Kilograms | Standard Deviation 1.989 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 29 DAY 1; n=3, 4 | -2.18 Kilograms | Standard Deviation 1.786 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 30 DAY 1; n=3, 4 | -3.25 Kilograms | Standard Deviation 0.379 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 31 DAY 1; n=3, 4 | -3.38 Kilograms | Standard Deviation 0.435 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 32 DAY 1; n=3, 4 | -3.05 Kilograms | Standard Deviation 0.1 |
| Sorafenib+Mapatumumab 30 mg/kg | Change From Baseline in Weight | CYCLE 33 DAY 1; n=2, 4 | -3.13 Kilograms | Standard Deviation 0.15 |
Secondary
Duration of Response-BICR Assessment
Duration of response is defined as time from first PR or CR to radiologic disease progression; in responders only. CR: Disappearance of intratumoral arterial enhancement in all target lesions. PR: At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the Baseline sum of the diameters of target lesions. Progressive disease (PD): An increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started.
Time frame: Randomization to maximum of 24.1 months
Population: mITT Population. Only responders were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib+Placebo | Duration of Response-BICR Assessment | 123 Days |
| Sorafenib+Mapatumumab 30 mg/kg | Duration of Response-BICR Assessment | 127 Days |
Secondary
Median Overall Survival
Overall survival is defined as time from randomization to death from any cause. The analysis was performed using Kaplan Meier methods. The median overall survival is reported with one-sided 90% confidence interval. NA indicates upper limit was not measurable as one-sided confidence interval is presented.
Time frame: Randomization to maximum of 52.9 months
Population: mITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib+Placebo | Median Overall Survival | 10.1 Months |
| Sorafenib+Mapatumumab 30 mg/kg | Median Overall Survival | 10.0 Months |
p-value: 0.6121Stratified log-rank test
Secondary
Number of Participants With Anti-mapatumumab Antibodies
Blood samples were collected for the assessment of serum antibodies. The presence of anti-mapatumumab antibodies was assessed using a validated electrochemiluminescent immunoassay. The assay incorporated a tiered testing approach which used screening and confirmation steps. The anti-drug antibody (ADA) confirmed positive participants were separated into transient or persistent antibody positives. Persistent positive refers to positive immunogenic response at 2 or more assessments or at the final assessment. Transient positive refers to positive immunogenic response at only 1 assessment and negative at the final assessment.
Time frame: Randomization to maximum of 24.1 months
Population: As-Treated Population. Only participants with an available immunogenicity assay were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sorafenib+Placebo | Number of Participants With Anti-mapatumumab Antibodies | Transient positive | 6 Participants |
| Sorafenib+Placebo | Number of Participants With Anti-mapatumumab Antibodies | Persistent positive | 7 Participants |
| Sorafenib+Placebo | Number of Participants With Anti-mapatumumab Antibodies | Negative | 36 Participants |
Secondary
Number of Participants With Severe AEs
An AE is any unfavorable or unintended sign, symptom, or disease that is temporally associated with the use of a study agent but is not necessarily caused by the study agent. Severity of AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0. Grade 1 represents mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 represents moderate; minimal, local or non-invasive intervention indicated. Grade 3 represents severe or medically significant but not immediately life -threatening; hospitalization or prolongation of hospitalization indicated; disabling. Grade 4 represents life -threatening consequences; urgent intervention indicated. Grade 5 represents death related to AE. Severe AE is defined as AEs classified by investigator as severe (causing inability to carry out usual activities), life threatening or fatal using NCI-CTCAE Version 4.0 grading.
Time frame: Start of study treatment to maximum of 52.9 months
Population: As-Treated Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sorafenib+Placebo | Number of Participants With Severe AEs | 42 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Severe AEs | 38 Participants |
Secondary
Number of Participants With Treatment-emergent Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any unfavorable or unintended sign, symptom, or disease that is temporally associated with the use of a study agent but is not necessarily caused by the study agent. An SAE is an adverse event resulting in any of the following outcomes: death, life-threatening, inpatient hospitalization, prolongation of an existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect or other medically important events that may jeopardize the participant or may require intervention to prevent one of the other outcomes mentioned before. A treatment-emergent AE is an AE that emerged during treatment, having been absent pre-treatment, or worsened relative to the pre-treatment state. As-Treated Population comprised of participants who received at least part of 1 dose of study agent analyzed according to the treatment that they actually received.
Time frame: Start of study treatment to maximum of 52.9 months
Population: As-Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sorafenib+Placebo | Number of Participants With Treatment-emergent Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) | Non-serious AEs | 47 Participants |
| Sorafenib+Placebo | Number of Participants With Treatment-emergent Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 27 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Treatment-emergent Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) | Non-serious AEs | 49 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Treatment-emergent Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 21 Participants |
Secondary
Number of Participants With Worst Toxicity Grade-chemistry Parameters
Blood samples were collected for the evaluation of following chemistry parameters: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), amylase, bilirubin, gamma glutamyl transferase (GGT), calcium, potassium, magnesium, albumin, sodium and creatinine. Laboratory toxicities were graded based on the NCI-CTCAE version 4.0. Grade 1 represents mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 represents moderate; minimal, local or non-invasive intervention indicated. Grade 3 represents severe or medically significant but not immediately life -threatening; hospitalization or prolongation of hospitalization indicated; disabling. Grade 4 represents life -threatening consequences; urgent intervention indicated. Number of participants with worst toxicity grades for any abnormalities observed in any chemistry parameters during the study is presented.
Time frame: Enrolment to maximum of 52.9 months
Population: As-Treated Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypermagnesemia; Grade 2; n=51, 50 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Bilirubin increased; Grade 1, n=51, 50 | 15 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypermagnesemia; Grade 3; n=51, 50 | 1 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | AST increased; Grade 0, n=51, 50 | 1 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypermagnesemia; Grade 4; n=51, 50 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Bilirubin increased; Grade 2, n=51, 50 | 17 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypernatremia; Grade 0, n=51, 50 | 18 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALP increased; Grade 1, n=51, 50 | 31 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypernatremia; Grade 1, n=51, 50 | 16 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Bilirubin increased; Grade 3, n=51, 50 | 7 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypernatremia; Grade 2, n=51, 50 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALT increased; Grade 1, n=51, 50 | 30 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypernatremia; Grade 3, n=51, 50 | 16 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Bilirubin increased; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypernatremia; Grade 4, n=51, 50 | 1 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALP increased; Grade 2, n=51, 50 | 11 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypoalbuminemia; Grade 0, n=51, 50 | 22 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | GGT increased; Grade 0, n=51, 50 | 1 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypoalbuminemia; Grade 1, n=51, 50 | 10 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | AST increased; Grade 1, n=51, 50 | 23 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypoalbuminemia; Grade 2, n=51, 50 | 18 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | GGT increased; Grade 1, n=51, 50 | 10 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypoalbuminemia; Grade 3, n=51, 50 | 1 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALP increased; Grade 3, n=51, 50 | 5 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypoalbuminemia; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | GGT increased; Grade 2, n=51, 50 | 14 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypocalcemia; Grade 0, n=50, 50 | 16 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALT increased; Grade 3, n=51, 50 | 7 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypocalcemia; Grade 1, n=50, 50 | 8 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | GGT increased; Grade 3, n=51, 50 | 23 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypocalcemia; Grade 2, n=50, 50 | 18 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALP increased; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypocalcemia; Grade 3, n=50, 50 | 6 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | GGT increased; Grade 4, n=51, 50 | 3 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypocalcemia; Grade 4, n=50, 50 | 2 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | AST increased; Grade 2, n=51, 50 | 10 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypokalemia; Grade 0, n=51, 50 | 37 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypercalcemia; Grade 0, n=49, 47 | 37 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypokalemia; Grade 1, n=51, 50 | 11 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Amylase increased; Grade 0, n=51, 50 | 30 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypokalemia; Grade 2, n=51, 50 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypercalcemia; Grade 1, n=49, 47 | 11 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypokalemia; Grade 3, n=51, 50 | 1 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALT increased; Grade 0, n=51, 50 | 6 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypokalemia; Grade 4, n=51, 50 | 2 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypercalcemia; Grade 2, n=49, 47 | 1 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypomagnesemia; Grade 0, n=51, 50 | 30 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Amylase increased; Grade 1, n=51, 50 | 9 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypomagnesemia; Grade 1, n=51, 50 | 19 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypercalcemia; Grade 3, n=49, 47 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypomagnesemia; Grade 2, n=51, 50 | 2 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | AST increased; Grade 3, n=51, 50 | 16 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypomagnesemia; Grade 3, n=51, 50 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypercalcemia; Grade 4, n=49, 47 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypomagnesemia; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Amylase increased; Grade 2, n=51, 50 | 5 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyponatremia; Grade 0, n=49, 47 | 40 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyperkalemia; Grade 0; n=51, 50 | 36 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyponatremia; Grade 1, n=49, 47 | 5 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALT increased; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyponatremia; Grade 2, n=49, 47 | 2 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyperkalemia; Grade 1; n=51, 50 | 2 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyponatremia; Grade 3, n=49, 47 | 2 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Amylase increased; Grade 3, n=51, 50 | 6 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyponatremia; Grade 4, n=49, 47 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyperkalemia; Grade 2; n=51, 50 | 10 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Lipase increased; Grade 0, n=51, 50 | 19 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | AST increased; Grade 4, n=51, 50 | 1 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Lipase increased; Grade 1, n=51, 50 | 5 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyperkalemia; Grade 3; n=51, 50 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Lipase increased; Grade 2, n=51, 50 | 8 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Lipase increased; Grade 3, n=51, 50 | 16 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Amylase increased; Grade 4, n=51, 50 | 1 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyperkalemia; Grade 4; n=51, 50 | 3 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Renal: Creatinine increased; Grade 2, n=51, 50 | 8 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALT increased; Grade 2, n=51, 50 | 8 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Renal: Creatinine increased; Grade 3, n=51, 50 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypermagnesemia; Grade 0; n=51, 50 | 29 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Bilirubin increased; Grade 0, n=51, 50 | 12 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Lipase increased; Grade 4, n=51, 50 | 3 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypermagnesemia; Grade 1; n=51, 50 | 21 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Renal: Creatinine increased; Grade 0, n=51, 50 | 36 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALP increased; Grade 0, n=51, 50 | 4 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Renal: Creatinine increased; Grade 1, n=51, 50 | 7 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Renal: Creatinine increased; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypoalbuminemia; Grade 2, n=51, 50 | 14 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALT increased; Grade 0, n=51, 50 | 4 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALT increased; Grade 1, n=51, 50 | 28 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALT increased; Grade 2, n=51, 50 | 9 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALT increased; Grade 3, n=51, 50 | 9 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALT increased; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | AST increased; Grade 0, n=51, 50 | 1 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | AST increased; Grade 1, n=51, 50 | 20 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | AST increased; Grade 2, n=51, 50 | 9 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | AST increased; Grade 3, n=51, 50 | 20 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | AST increased; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALP increased; Grade 0, n=51, 50 | 8 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALP increased; Grade 1, n=51, 50 | 26 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALP increased; Grade 2, n=51, 50 | 11 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALP increased; Grade 3, n=51, 50 | 5 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | ALP increased; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Amylase increased; Grade 0, n=51, 50 | 22 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Amylase increased; Grade 1, n=51, 50 | 17 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Amylase increased; Grade 2, n=51, 50 | 8 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Amylase increased; Grade 3, n=51, 50 | 3 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Amylase increased; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Bilirubin increased; Grade 0, n=51, 50 | 9 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Bilirubin increased; Grade 1, n=51, 50 | 10 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Bilirubin increased; Grade 2, n=51, 50 | 16 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Bilirubin increased; Grade 3, n=51, 50 | 13 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Bilirubin increased; Grade 4, n=51, 50 | 2 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | GGT increased; Grade 0, n=51, 50 | 2 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | GGT increased; Grade 1, n=51, 50 | 13 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | GGT increased; Grade 2, n=51, 50 | 15 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | GGT increased; Grade 3, n=51, 50 | 18 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | GGT increased; Grade 4, n=51, 50 | 2 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypercalcemia; Grade 0, n=49, 47 | 37 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypercalcemia; Grade 1, n=49, 47 | 9 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypercalcemia; Grade 2, n=49, 47 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypercalcemia; Grade 3, n=49, 47 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypercalcemia; Grade 4, n=49, 47 | 1 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyperkalemia; Grade 0; n=51, 50 | 27 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyperkalemia; Grade 1; n=51, 50 | 3 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyperkalemia; Grade 2; n=51, 50 | 10 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyperkalemia; Grade 3; n=51, 50 | 7 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyperkalemia; Grade 4; n=51, 50 | 3 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypermagnesemia; Grade 0; n=51, 50 | 28 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypermagnesemia; Grade 1; n=51, 50 | 19 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypermagnesemia; Grade 2; n=51, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypermagnesemia; Grade 3; n=51, 50 | 3 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypermagnesemia; Grade 4; n=51, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypernatremia; Grade 0, n=51, 50 | 18 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypernatremia; Grade 1, n=51, 50 | 14 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypernatremia; Grade 2, n=51, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypernatremia; Grade 3, n=51, 50 | 15 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypernatremia; Grade 4, n=51, 50 | 3 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypoalbuminemia; Grade 0, n=51, 50 | 26 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypoalbuminemia; Grade 1, n=51, 50 | 9 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Lipase increased; Grade 2, n=51, 50 | 8 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypoalbuminemia; Grade 3, n=51, 50 | 1 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypoalbuminemia; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypocalcemia; Grade 0, n=50, 50 | 15 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypocalcemia; Grade 1, n=50, 50 | 14 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypocalcemia; Grade 2, n=50, 50 | 19 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypocalcemia; Grade 3, n=50, 50 | 2 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypocalcemia; Grade 4, n=50, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypokalemia; Grade 0, n=51, 50 | 41 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypokalemia; Grade 1, n=51, 50 | 8 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypokalemia; Grade 2, n=51, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypokalemia; Grade 3, n=51, 50 | 1 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypokalemia; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypomagnesemia; Grade 0, n=51, 50 | 35 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypomagnesemia; Grade 1, n=51, 50 | 13 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypomagnesemia; Grade 2, n=51, 50 | 1 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypomagnesemia; Grade 3, n=51, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hypomagnesemia; Grade 4, n=51, 50 | 1 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyponatremia; Grade 0, n=49, 47 | 32 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyponatremia; Grade 1, n=49, 47 | 10 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyponatremia; Grade 2, n=49, 47 | 3 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyponatremia; Grade 3, n=49, 47 | 2 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Hyponatremia; Grade 4, n=49, 47 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Lipase increased; Grade 0, n=51, 50 | 13 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Lipase increased; Grade 1, n=51, 50 | 6 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Lipase increased; Grade 3, n=51, 50 | 17 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Renal: Creatinine increased; Grade 1, n=51, 50 | 12 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Renal: Creatinine increased; Grade 2, n=51, 50 | 3 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Renal: Creatinine increased; Grade 3, n=51, 50 | 1 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Renal: Creatinine increased; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Lipase increased; Grade 4, n=51, 50 | 6 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-chemistry Parameters | Renal: Creatinine increased; Grade 0, n=51, 50 | 34 Participants |
Secondary
Number of Participants With Worst Toxicity Grade-hematology Parameters
Blood samples were collected for assessment of the following hematology parameters: activated partial thromboplastin time (APTT), hemoglobin, international normalized ratio (INR), lymphocytes, neutrophils, platelets and white blood cells (WBC). Laboratory toxicities were graded based on the NCI-CTCAE version 4.0. Grade 1 represents mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 represents moderate; minimal, local or non-invasive intervention indicated. Grade 3 represents severe or medically significant but not immediately life -threatening; hospitalization or prolongation of hospitalization indicated; disabling. Grade 4 represents life -threatening consequences; urgent intervention indicated. Number of participants with worst toxicity grades for any abnormalities observed in any hematology parameters during the study is presented.
Time frame: Enrolment to maximum of 52.9 months
Population: As-Treated Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | APTT prolonged; Grade 0, n=51, 50 | 24 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | APTT prolonged; Grade 1, n=51, 50 | 19 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | APTT prolonged; Grade 2, n=51, 50 | 6 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | APTT prolonged; Grade 3, n=51, 50 | 2 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | APTT prolonged; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Anemia; Grade 0, n=51, 50 | 13 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Anemia; Grade 1, n=51, 50 | 23 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Anemia; Grade 2, n=51, 50 | 9 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Anemia; Grade 3, n=51, 50 | 6 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Anemia; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Hemoglobin increased; Grade 0, n=46, 44 | 46 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Hemoglobin increased; Grade 1, n=46, 44 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Hemoglobin increased; Grade 2, n=46, 44 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Hemoglobin increased; Grade 3, n=46, 44 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Hemoglobin increased; Grade 4, n=46, 44 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | INR increased; Grade 0, n=51, 50 | 2 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | INR increased; Grade 1, n=51, 50 | 35 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | INR increased; Grade 2, n=51, 50 | 12 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | INR increased; Grade 3, n=51, 50 | 2 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | INR increased; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes decreased; Grade 0, n=51, 50 | 24 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes decreased; Grade 1, n=51, 50 | 3 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes decreased; Grade 2, n=51, 50 | 16 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes decreased; Grade 3, n=51, 50 | 8 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes decreased; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes increased; Grade 0, n=51, 49 | 49 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes increased; Grade 1, n=51, 49 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes increased; Grade 2, n=51, 49 | 2 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes increased; Grade 3, n=51, 49 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes increased; Grade 4, n=51, 49 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Neutrophil count decreased; Grade 0, n=51, 50 | 39 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Neutrophil count decreased; Grade 1, n=51, 50 | 3 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Neutrophil count decreased; Grade 2, n=51, 50 | 8 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Neutrophil count decreased; Grade 3, n=51, 50 | 1 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Neutrophil count decreased; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Platelets decreased; Grade 0, n=51, 50 | 21 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Platelets decreased; Grade 1, n=51, 50 | 12 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Platelets decreased; Grade 2, n=51, 50 | 10 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Platelets decreased; Grade 3, n=51, 50 | 7 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | Platelets decreased; Grade 4, n=51, 50 | 1 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | WBC decreased; Grade 0, n=51, 50 | 33 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | WBC decreased; Grade 1, n=51, 50 | 10 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | WBC decreased; Grade 2, n=51, 50 | 8 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | WBC decreased; Grade 3, n=51, 50 | 0 Participants |
| Sorafenib+Placebo | Number of Participants With Worst Toxicity Grade-hematology Parameters | WBC decreased; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes decreased; Grade 2, n=51, 50 | 18 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | APTT prolonged; Grade 0, n=51, 50 | 22 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Platelets decreased; Grade 4, n=51, 50 | 2 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | APTT prolonged; Grade 1, n=51, 50 | 24 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes decreased; Grade 3, n=51, 50 | 8 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | APTT prolonged; Grade 2, n=51, 50 | 2 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Neutrophil count decreased; Grade 4, n=51, 50 | 3 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | APTT prolonged; Grade 3, n=51, 50 | 2 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes decreased; Grade 4, n=51, 50 | 1 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | APTT prolonged; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | WBC decreased; Grade 2, n=51, 50 | 5 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Anemia; Grade 0, n=51, 50 | 9 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes increased; Grade 0, n=51, 49 | 45 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Anemia; Grade 1, n=51, 50 | 22 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Platelets decreased; Grade 0, n=51, 50 | 21 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Anemia; Grade 2, n=51, 50 | 16 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes increased; Grade 1, n=51, 49 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Anemia; Grade 3, n=51, 50 | 3 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | WBC decreased; Grade 0, n=51, 50 | 30 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Anemia; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes increased; Grade 2, n=51, 49 | 4 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Hemoglobin increased; Grade 0, n=46, 44 | 44 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Platelets decreased; Grade 1, n=51, 50 | 16 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Hemoglobin increased; Grade 1, n=46, 44 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes increased; Grade 3, n=51, 49 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Hemoglobin increased; Grade 2, n=46, 44 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | WBC decreased; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Hemoglobin increased; Grade 3, n=46, 44 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes increased; Grade 4, n=51, 49 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Hemoglobin increased; Grade 4, n=46, 44 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Platelets decreased; Grade 2, n=51, 50 | 6 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | INR increased; Grade 0, n=51, 50 | 3 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Neutrophil count decreased; Grade 0, n=51, 50 | 37 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | INR increased; Grade 1, n=51, 50 | 30 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | WBC decreased; Grade 1, n=51, 50 | 12 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | INR increased; Grade 2, n=51, 50 | 14 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Neutrophil count decreased; Grade 1, n=51, 50 | 2 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | INR increased; Grade 3, n=51, 50 | 3 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Platelets decreased; Grade 3, n=51, 50 | 5 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | INR increased; Grade 4, n=51, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Neutrophil count decreased; Grade 2, n=51, 50 | 7 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes decreased; Grade 0, n=51, 50 | 23 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | WBC decreased; Grade 3, n=51, 50 | 3 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Lymphocytes decreased; Grade 1, n=51, 50 | 0 Participants |
| Sorafenib+Mapatumumab 30 mg/kg | Number of Participants With Worst Toxicity Grade-hematology Parameters | Neutrophil count decreased; Grade 3, n=51, 50 | 1 Participants |
Secondary
Percentage of Participants With Disease Control-BICR Assessment
Disease control rate is the percentage of participants with complete response+partial response+stable disease according to mRECIST criteria for hepatocellular carcinoma. The end point was based on BICR assessment of imaging scans. The percentage of participants with disease control is presented along with 95% confidence interval.
Time frame: Randomization to maximum of 24.1 months
Population: mITT Population. Only those participants who had their BICR scans read and having available assessment for best response were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sorafenib+Placebo | Percentage of Participants With Disease Control-BICR Assessment | 92.5 Percentage of participants |
| Sorafenib+Mapatumumab 30 mg/kg | Percentage of Participants With Disease Control-BICR Assessment | 71.8 Percentage of participants |
p-value: 0.019895% CI: [-40.8, 1.8]Fisher Exact
Secondary
Percentage of Participants With Disease Control-Investigator Assessment
Disease control rate is the percentage of participants with complete response+partial response+stable disease according to mRECIST criteria for hepatocellular carcinoma to investigator assessments. The percentage of participants with disease control is presented along with 95% confidence interval.
Time frame: Randomization to maximum of 52.9 months
Population: mITT Population. Only those participants with available assessment for best response were analyzed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sorafenib+Placebo | Percentage of Participants With Disease Control-Investigator Assessment | 74.5 Percentage of participants |
| Sorafenib+Mapatumumab 30 mg/kg | Percentage of Participants With Disease Control-Investigator Assessment | 68.8 Percentage of participants |
p-value: 0.655895% CI: [-25.4, 13.8]Fisher Exact
Secondary
Percentage of Participants With Objective Response-BICR Assessment
Objective response rate is defined as the percentage of participants with complete response+partial response according to mRECIST criteria for hepatocellular carcinoma using BICR assessment of imaging scans. The percentage of participants with objective response is reported along with 95% confidence interval.
Time frame: Randomization to maximum of 24.1 months
Population: mITT Population. Only those participants who had their BICR scans read and having available assessment for best response were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sorafenib+Placebo | Percentage of Participants With Objective Response-BICR Assessment | 12.5 Percentage of participants |
| Sorafenib+Mapatumumab 30 mg/kg | Percentage of Participants With Objective Response-BICR Assessment | 17.9 Percentage of participants |
p-value: 0.545895% CI: [-16.8, 26.6]Fisher Exact
Secondary
Percentage of Participants With Objective Response-Investigator Assessment
Objective response rate is defined as the percentage of participants with complete response+partial response according to mRECIST criteria for hepatocellular carcinoma to investigator assessments. The percentage of participants with objective response is reported along with 95% confidence interval.
Time frame: Randomization to maximum of 52.9 months
Population: mITT Population. Only those participants with available assessment for best response were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sorafenib+Placebo | Percentage of Participants With Objective Response-Investigator Assessment | 7.8 Percentage of participants |
| Sorafenib+Mapatumumab 30 mg/kg | Percentage of Participants With Objective Response-Investigator Assessment | 14.6 Percentage of participants |
p-value: 0.347995% CI: [-13.4, 26.2]Fisher Exact
Secondary
Progression Free Survival-BICR Assessment
Progression free survival is defined as time from randomization to radiologic disease progression or death from any cause. The analysis was performed using Kaplan Meier methods using BICR assessment of imaging scans. The median progression free survival is reported with one-sided 90% confidence interval. NA indicates upper limit was not measurable as one-sided confidence interval is presented.
Time frame: Randomization to maximum of 24.1 months
Population: mITT Population. Only those participants who had their BICR scans read were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib+Placebo | Progression Free Survival-BICR Assessment | 4.3 Months |
| Sorafenib+Mapatumumab 30 mg/kg | Progression Free Survival-BICR Assessment | 3.2 Months |
p-value: 0.6925Stratified log-rank test
Secondary
Progression Free Survival-Investigator Assessment
Progression free survival is defined as time from randomization to radiologic disease progression or death from any cause. The analysis was performed using Kaplan Meier methods based on application of mRECIST for hepatocellular carcinoma to investigator assessments. The median progression free survival is reported with one-sided 90% confidence interval. NA indicates upper limit was not measurable as one-sided confidence interval is presented.
Time frame: Randomization to maximum of 52.9 months
Population: mITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib+Placebo | Progression Free Survival-Investigator Assessment | 5.4 Months |
| Sorafenib+Mapatumumab 30 mg/kg | Progression Free Survival-Investigator Assessment | 4.0 Months |
p-value: 0.3088Stratified log-rank test
Secondary
Serum Concentration of Mapatumumab
Blood samples were collected for determination of serum mapatumumab concentration at the indicated time points. NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time points.
Time frame: Day1 pre-dose(Cycle 1,2,4,5,6,8,9,10,12,14,16,17,18,20,22,24,26,28,30,32,34);end of infusion (Cycle 1);Day8 pre-dose(Cycle 1);Day15 pre-dose (Cycle 1,2);Day21(Cycle 2,4,6,8,9,12,14,16,18,20,22,24,26,28,30,32,34);Cycle 99(end of treatment) (21-day cycles)
Population: As Treated Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 1 Day 1, pre-dose, n=46 | 638.4 Nanograms per milliliter | Standard Deviation 2668.01 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 1 DAY 1,end of infusion, n=46 | 555157.6 Nanograms per milliliter | Standard Deviation 260848.85 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 1; DAY 8, pre-dose; n=40 | 250229.9 Nanograms per milliliter | Standard Deviation 89714.76 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 1 DAY 15, pre-dose; n=1 | 121556.0 Nanograms per milliliter | — |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 2 DAY 1, pre-dose; n=40 | 126588.4 Nanograms per milliliter | Standard Deviation 149231.45 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 2 DAY 15, pre-dose; n=3 | 128839.0 Nanograms per milliliter | Standard Deviation 153667.78 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 2 DAY 21; n=28 | 180606.6 Nanograms per milliliter | Standard Deviation 109893.28 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 4 DAY 1, pre-dose; n=31 | 194936.8 Nanograms per milliliter | Standard Deviation 142242.8 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 5, DAY 1, pre-dose; n=1 | 223681.0 Nanograms per milliliter | — |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 6, DAY 1, pre-dose; n=21 | 160741.5 Nanograms per milliliter | Standard Deviation 64893.03 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 6, DAY 21; n=20 | 201237.7 Nanograms per milliliter | Standard Deviation 75352.54 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 8, DAY 1, pre-dose; n=21 | 246616.5 Nanograms per milliliter | Standard Deviation 204363.04 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 8, DAY 21; n=17 | 187927.6 Nanograms per milliliter | Standard Deviation 104803.16 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 9, DAY 1, pre-dose; n=1 | 136122.0 Nanograms per milliliter | — |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 10, DAY 1, pre-dose; n=16 | 204147.1 Nanograms per milliliter | Standard Deviation 103243.21 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 10, DAY 21; n=15 | 219503.0 Nanograms per milliliter | Standard Deviation 105968.15 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 12, DAY 1, pre-dose; n=12 | 200141.1 Nanograms per milliliter | Standard Deviation 93093.68 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 12, DAY 21; n=11 | 256924.5 Nanograms per milliliter | Standard Deviation 111904.82 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 14, DAY 1, pre-dose; n=9 | 207930.6 Nanograms per milliliter | Standard Deviation 84247.04 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 14, DAY 21 n=9 | 256779.4 Nanograms per milliliter | Standard Deviation 127463.67 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 16, DAY 1, pre-dose; n=9 | 196074.3 Nanograms per milliliter | Standard Deviation 100377.45 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 16, DAY 21; n=8 | 253521.0 Nanograms per milliliter | Standard Deviation 87675.77 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 17, DAY 1, pre-dose; n=1 | 156161.0 Nanograms per milliliter | — |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 18, DAY 1, pre-dose; n=8 | 199379.4 Nanograms per milliliter | Standard Deviation 61011.54 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 18, DAY 21; n=7 | 229539.1 Nanograms per milliliter | Standard Deviation 86440.46 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 20 DAY 1, pre-dose; n=8 | 189486.6 Nanograms per milliliter | Standard Deviation 54097.82 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 20, DAY 21; n=7 | 222443.7 Nanograms per milliliter | Standard Deviation 86046.38 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 22 DAY 1, pre-dose; n=8 | 208485.4 Nanograms per milliliter | Standard Deviation 80252.29 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 22, DAY 21; n=7 | 212481.1 Nanograms per milliliter | Standard Deviation 110103.79 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 24 DAY 1, pre-dose; n=8 | 219439.8 Nanograms per milliliter | Standard Deviation 71740.01 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 24, DAY 21; n=7 | 221249.1 Nanograms per milliliter | Standard Deviation 73317.41 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 26 DAY 1, pre-dose; n=4 | 223427.3 Nanograms per milliliter | Standard Deviation 67101.56 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 26, DAY 21; n=4 | 295941.5 Nanograms per milliliter | Standard Deviation 100208.45 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 28 DAY 1, pre-dose; n=3 | 219802.7 Nanograms per milliliter | Standard Deviation 115484.98 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 28, DAY 21; n=2 | 173018.5 Nanograms per milliliter | Standard Deviation 54870.78 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 30 DAY 1, pre-dose; n=2 | 173200.5 Nanograms per milliliter | Standard Deviation 13447.05 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 30, DAY 21; n=2 | 180484.5 Nanograms per milliliter | Standard Deviation 14783.48 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 32 DAY 1, pre-dose; n=1 | 178275.0 Nanograms per milliliter | — |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 32, DAY 21; n=1 | 177496.0 Nanograms per milliliter | — |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 34 DAY 1, pre-dose; n=1 | 150553.0 Nanograms per milliliter | — |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 34, DAY 21; n=1 | 134781.0 Nanograms per milliliter | — |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 99, end of treatment; n=14 | 86640.1 Nanograms per milliliter | Standard Deviation 64981.14 |
| Sorafenib+Placebo | Serum Concentration of Mapatumumab | CYCLE 4, DAY 21; n=23 | 183754.3 Nanograms per milliliter | Standard Deviation 93584.71 |
Secondary
Time to Progression-Investigator Assessment
Time to progression is defined as the time from randomization to radiologic disease progression. The primary analysis was performed using Kaplan Meier methods based on application of mRECIST for hepatocellular carcinoma to investigator assessments. The median time to progression is reported with one-sided 90% confidence interval. NA indicates upper limit was not measurable as one-sided confidence interval is presented.
Time frame: Randomization to maximum of 52.9 months
Population: mITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib+Placebo | Time to Progression-Investigator Assessment | 8.3 Months |
| Sorafenib+Mapatumumab 30 mg/kg | Time to Progression-Investigator Assessment | 6.4 Months |
p-value: 0.3156Stratified log-rank test
Secondary
Time to Response-BICR Assessment
Time to response is defined as time from randomization to first partial response or complete response in responders only. Complete Response (CR): Disappearance of intratumoral arterial enhancement in all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions
Time frame: Randomization to maximum of 24.1 months
Population: mITT Population. Only responders were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib+Placebo | Time to Response-BICR Assessment | 44 Days |
| Sorafenib+Mapatumumab 30 mg/kg | Time to Response-BICR Assessment | 48 Days |