Trial Outcomes & Findings for Patients With Metastatic Colorectal Cancer Treated With Regorafenib or Placebo After Failure of Standard Therapy (NCT NCT01103323)

Last Updated: 2015-06-24

Results Overview

Overall survival (OS) was defined as the time (days) from randomization to death due to any cause. Patients alive at the time of analysis were censored at the last date known to be alive. If a patient was lost to follow-up and there was no contact after randomization, this patient was censored at Day 1.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

760 participants

Primary outcome timeframe

From randomization of the first subject until the database cut-off approximately 14 months later (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis (IA).

Results posted on

2015-06-24

Participant Flow

Participant milestones

Participant milestones
Measure	Regorafenib (Stivarga, BAY73-4506)+BSC Participants received Regorafenib 160 mg per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC).	Placebo+BSC Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC). Period 1 is placebo and placebo-regorafenib with placebo period only before unblinding. Period 2 is placebo-regorafenib with regorafenib period only.
Without/Before Drug Switch STARTED	505	255
Without/Before Drug Switch Participants Received Treatment	500	253
Without/Before Drug Switch COMPLETED	429	237
Without/Before Drug Switch NOT COMPLETED	76	18
Switched From Placebo to Regorafenib STARTED	0	4
Switched From Placebo to Regorafenib COMPLETED	0	3
Switched From Placebo to Regorafenib NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Regorafenib (Stivarga, BAY73-4506)+BSC Participants received Regorafenib 160 mg per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC).	Placebo+BSC Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC). Period 1 is placebo and placebo-regorafenib with placebo period only before unblinding. Period 2 is placebo-regorafenib with regorafenib period only.
Without/Before Drug Switch Adverse Event	50	7
Without/Before Drug Switch Withdrawal by Subject	17	5
Without/Before Drug Switch Protocol Violation	2	0
Without/Before Drug Switch Physician Decision	2	0
Without/Before Drug Switch did not receive study treatment	5	2
Without/Before Drug Switch Switch to Regorafenib	0	4
Switched From Placebo to Regorafenib Adverse Event	0	1

Baseline Characteristics

Patients With Metastatic Colorectal Cancer Treated With Regorafenib or Placebo After Failure of Standard Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Regorafenib (Stivarga, BAY73-4506)+BSC n=505 Participants Participants received Regorafenib 160 mg per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC).	Placebo+BSC n=255 Participants Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC).	Total n=760 Participants Total of all reporting groups
Age, Continuous	60.7 Years n=99 Participants	60.1 Years n=107 Participants	60.5 Years n=206 Participants
Sex: Female, Male Female	194 Participants n=99 Participants	102 Participants n=107 Participants	296 Participants n=206 Participants
Sex: Female, Male Male	311 Participants n=99 Participants	153 Participants n=107 Participants	464 Participants n=206 Participants
Eastern Cooperative Oncology Group (ECOG) performance status (PS) before treatment 0	265 Participants n=99 Participants	146 Participants n=107 Participants	411 Participants n=206 Participants
Eastern Cooperative Oncology Group (ECOG) performance status (PS) before treatment 1	240 Participants n=99 Participants	109 Participants n=107 Participants	349 Participants n=206 Participants
KRAS mutation No	205 Participants n=99 Participants	94 Participants n=107 Participants	299 Participants n=206 Participants
KRAS mutation Yes	273 Participants n=99 Participants	157 Participants n=107 Participants	430 Participants n=206 Participants
KRAS mutation Unknown	27 Participants n=99 Participants	4 Participants n=107 Participants	31 Participants n=206 Participants

PRIMARY outcome

Timeframe: From randomization of the first subject until the database cut-off approximately 14 months later (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis (IA).

Population: Intent to treat (ITT)

Outcome measures

Outcome measures
Measure	Regorafenib (Stivarga, BAY73-4506)+BSC n=505 Participants Participants received Regorafenib 160 mg per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC).	Placebo+BSC n=255 Participants Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC)
Overall Survival	196 Days Interval 178.0 to 222.0	151 Days Interval 134.0 to 177.0

SECONDARY outcome

Timeframe: From randomization of the first subject until the database cut-off approximately 14 months later (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals.

Population: ITT

Progression-free survival was defined as the time (days) from date of randomization to date of first observed disease progression (radiological or clinical) or death due to any cause, if death occurred before progression was documented.

Outcome measures

Outcome measures
Measure	Regorafenib (Stivarga, BAY73-4506)+BSC n=505 Participants Participants received Regorafenib 160 mg per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC).	Placebo+BSC n=255 Participants Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC)
Progression-free Survival (Based on Investigator's Assessment)	59 Days Interval 57.0 to 65.0	52 Days Interval 51.0 to 53.0

SECONDARY outcome

Population: ITT

The objective tumor response was defined as the percentage of patients with complete response (CR, tumor disappears) or partial response (PR, sum of lesion sizes decreased at least 30% from baseline) as best overall response. A best overall response was defined for all patients, using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1. Patients whose best overall response was not CR or PR, and any patients with no post-baseline assessments were considered nonresponders for the analysis.

Outcome measures

Outcome measures
Measure	Regorafenib (Stivarga, BAY73-4506)+BSC n=505 Participants Participants received Regorafenib 160 mg per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC).	Placebo+BSC n=255 Participants Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC)
Objective Tumor Response	1.0 Percentage of participants	0.4 Percentage of participants

SECONDARY outcome

Population: ITT

Disease control was defined as the percentage of patients whose best response was not PD \[sum of lesion sizes increased at least 20% from smallest sum on study or new lesions\] (ie, CR \[tumor disappears\], PR \[sum of lesion sizes decreased at least 30% from baseline\] or SD (stable disease)). SD included if at least 6 weeks after randomization.

Outcome measures

Outcome measures
Measure	Regorafenib (Stivarga, BAY73-4506)+BSC n=505 Participants Participants received Regorafenib 160 mg per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC).	Placebo+BSC n=255 Participants Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC)
Disease Control	41.0 Percentage of participants	14.9 Percentage of participants

SECONDARY outcome

Population: ITT

A tumor response (best overall response) was defined for all patients, using the RECIST criteria, version 1.1. Categories: complete response (CR, tumor disappears), partial response (PR, sum of lesion sizes decreased at least 30% from baseline), stable disease (SD, steady state of disease), progressive disease (PD, sum of lesion sizes increased at least 20% from smallest sum on study or new lesions). Clinical PD considered when radiographic imaging not possible.

Outcome measures

Outcome measures
Measure	Regorafenib (Stivarga, BAY73-4506)+BSC n=505 Participants Participants received Regorafenib 160 mg per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC).	Placebo+BSC n=255 Participants Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC)
Tumor Response Complete Response (CR)	0 Percentage of participants	0 Percentage of participants
Tumor Response Partial Response (PR)	1.0 Percentage of participants	0.4 Percentage of participants
Tumor Response Stable Disease (SD)	42.8 Percentage of participants	14.5 Percentage of participants
Tumor Response Progressive Disease (PD)	49.5 Percentage of participants	80.0 Percentage of participants
Tumor Response Non CR/Non PD	0.8 Percentage of participants	0.4 Percentage of participants
Tumor Response Not applicable	0.2 Percentage of participants	0 Percentage of participants
Tumor Response Not assessed	5.7 Percentage of participants	4.7 Percentage of participants

Adverse Events

Regorafenib (BAY73-4506)+BSC

Serious events: 232 serious events

Other events: 489 other events

Deaths: 0 deaths

Placebo+BSC

Serious events: 103 serious events

Other events: 229 other events

Deaths: 0 deaths

Placebo - Regorafenib After Unblinding

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Therapeutic Area Head

BAYER

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The agreed point of publication is 12-18 months after database lock at the earliest. Bayer will have 30-45 days to review publications, and may request an additional publication delay of up to 60 days to allow for filing a Patent Application (if applicable). No publication of single center data should be done prior of publication if multi-center data.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Regorafenib (BAY73-4506)+BSC n=500 participants at risk Participants received Regorafenib 160 mg per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC).	Placebo+BSC n=253 participants at risk Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC). It is for placebo period only before unblinding.	Placebo - Regorafenib After Unblinding n=4 participants at risk Participants in the placebo+BSC group switched to treatment with Regorafenib after unblinding. It is for Regorafenib treatment period only
Blood and lymphatic system disorders DIC	0.40% 2/500 • Number of events 2 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Blood and lymphatic system disorders Edema: Limb	0.20% 1/500 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.40% 1/253 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Blood and lymphatic system disorders Edema: Trunk/Genital	0.00% 0/500 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.79% 2/253 • Number of events 4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Blood and lymphatic system disorders Edema: Viscera	0.00% 0/500 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.40% 1/253 • Number of events 3 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Blood and lymphatic system disorders Hemoglobin	0.80% 4/500 • Number of events 8 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.79% 2/253 • Number of events 2 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Blood and lymphatic system disorders INR	0.40% 2/500 • Number of events 5 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Blood and lymphatic system disorders Neutrophils	0.20% 1/500 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Blood and lymphatic system disorders Platelets	0.40% 2/500 • Number of events 2 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Blood and lymphatic system disorders Thrombotic microangiopathy	0.20% 1/500 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Cardiac disorders Cardiac arrhythmia - Other	0.20% 1/500 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Cardiac disorders Cardiac ischemia/infarction	1.2% 6/500 • Number of events 6 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.40% 1/253 • Number of events 2 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Cardiac disorders Hypertension	0.20% 1/500 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Cardiac disorders Hypotension	0.40% 2/500 • Number of events 2 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Cardiac disorders Left ventricular systolic dysfunction	0.20% 1/500 • Number of events 3 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Cardiac disorders Supraventricular arrhythmia, Atrial fibrillation	0.40% 2/500 • Number of events 2 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Cardiac disorders cTnT	0.20% 1/500 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Eye disorders Diplopia	0.20% 1/500 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.40% 1/253 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Eye disorders Ocular - Other	0.20% 1/500 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Anorexia	1.0% 5/500 • Number of events 8 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.79% 2/253 • Number of events 2 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Ascites	0.20% 1/500 • Number of events 2 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.79% 2/253 • Number of events 2 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	25.0% 1/4 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Constipation	0.20% 1/500 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Dehydration	0.60% 3/500 • Number of events 3 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.79% 2/253 • Number of events 2 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Diarrhea	1.6% 8/500 • Number of events 9 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Distension	0.20% 1/500 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Enteritis	0.20% 1/500 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Fistula, GI, Abdomen NOS	0.20% 1/500 • Number of events 2 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.40% 1/253 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Fistula, GI, Anus	0.20% 1/500 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Fistula, GI, Small bowel NOS	0.20% 1/500 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders GI - Other	0.20% 1/500 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.40% 1/253 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Hemorrhoids	0.20% 1/500 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Ileus	0.40% 2/500 • Number of events 3 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	1.2% 3/253 • Number of events 3 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Mucositis (functional/symptomatic), Small bowel	0.20% 1/500 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Necrosis, GI, Peritoneal cavity	0.20% 1/500 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Obstruction, GI, Colon	1.8% 9/500 • Number of events 11 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	2.4% 6/253 • Number of events 8 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Obstruction, GI, Ileum	0.00% 0/500 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.40% 1/253 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Obstruction, GI, Small bowel NOS	0.80% 4/500 • Number of events 5 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	2.8% 7/253 • Number of events 9 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Obstruction, GI, Stomach	0.20% 1/500 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Perforation, GI, Colon	0.00% 0/500 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.40% 1/253 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Stricture, GI, Biliary tree	0.20% 1/500 • Number of events 2 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Ulcer, GI, Duodenum	0.20% 1/500 • Number of events 2 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)

Other adverse events
Measure	Regorafenib (BAY73-4506)+BSC n=500 participants at risk Participants received Regorafenib 160 mg per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC).	Placebo+BSC n=253 participants at risk Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus best supportive care (BSC). It is for placebo period only before unblinding.	Placebo - Regorafenib After Unblinding n=4 participants at risk Participants in the placebo+BSC group switched to treatment with Regorafenib after unblinding. It is for Regorafenib treatment period only
Blood and lymphatic system disorders Edema: Limb	9.8% 49/500 • Number of events 57 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	6.3% 16/253 • Number of events 19 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Blood and lymphatic system disorders Hemoglobin	15.2% 76/500 • Number of events 142 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	11.5% 29/253 • Number of events 46 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Blood and lymphatic system disorders Platelets	15.8% 79/500 • Number of events 136 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	2.4% 6/253 • Number of events 9 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	25.0% 1/4 • Number of events 2 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Cardiac disorders Hypertension	31.0% 155/500 • Number of events 213 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	8.3% 21/253 • Number of events 23 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	25.0% 1/4 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Endocrine disorders Hypothyroidism	5.4% 27/500 • Number of events 29 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.40% 1/253 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	25.0% 1/4 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Eye disorders Ocular - Other	1.0% 5/500 • Number of events 5 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	25.0% 1/4 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Anorexia	47.8% 239/500 • Number of events 388 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	28.9% 73/253 • Number of events 96 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Ascites	4.6% 23/500 • Number of events 24 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	2.4% 6/253 • Number of events 8 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	25.0% 1/4 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Constipation	23.8% 119/500 • Number of events 147 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	19.0% 48/253 • Number of events 58 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Diarrhea	43.6% 218/500 • Number of events 514 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	17.4% 44/253 • Number of events 57 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	50.0% 2/4 • Number of events 2 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Fistula, GI, Colon/Cecum/Appendix	0.00% 0/500 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	25.0% 1/4 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Mucositis (functional/symptomatic), Oral cavity	29.0% 145/500 • Number of events 267 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	4.7% 12/253 • Number of events 12 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Nausea	23.0% 115/500 • Number of events 162 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	21.7% 55/253 • Number of events 67 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	25.0% 1/4 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Taste alteration	7.8% 39/500 • Number of events 44 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	2.4% 6/253 • Number of events 6 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Gastrointestinal disorders Vomiting	17.0% 85/500 • Number of events 144 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	16.2% 41/253 • Number of events 50 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	25.0% 1/4 • Number of events 3 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
General disorders Constitutional symptoms - Other	6.0% 30/500 • Number of events 33 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	6.7% 17/253 • Number of events 19 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
General disorders Fatigue	63.6% 318/500 • Number of events 612 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	45.5% 115/253 • Number of events 168 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
General disorders Fever	27.2% 136/500 • Number of events 189 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	15.8% 40/253 • Number of events 48 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	50.0% 2/4 • Number of events 3 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
General disorders Flu-like syndrome	5.4% 27/500 • Number of events 30 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	2.4% 6/253 • Number of events 8 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	25.0% 1/4 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
General disorders Insomnia	7.8% 39/500 • Number of events 43 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	5.5% 14/253 • Number of events 15 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
General disorders Pain, Abdomen NOS	24.2% 121/500 • Number of events 239 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	18.6% 47/253 • Number of events 53 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
General disorders Pain, Back	15.8% 79/500 • Number of events 114 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	9.9% 25/253 • Number of events 27 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
General disorders Pain, Buttock	0.80% 4/500 • Number of events 5 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/253 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	25.0% 1/4 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
General disorders Pain, Chest/Thorax NOS	5.2% 26/500 • Number of events 29 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	4.7% 12/253 • Number of events 14 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
General disorders Pain, Extremity - limb	10.2% 51/500 • Number of events 83 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	5.5% 14/253 • Number of events 19 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
General disorders Pain, Head/Headache	10.0% 50/500 • Number of events 65 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	7.1% 18/253 • Number of events 23 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
General disorders Pain, Joint	6.4% 32/500 • Number of events 34 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	5.1% 13/253 • Number of events 14 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
General disorders Pain, Muscle	10.0% 50/500 • Number of events 64 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	5.5% 14/253 • Number of events 16 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
General disorders Pain, Throat/Pharynx/Larynx	1.8% 9/500 • Number of events 12 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.40% 1/253 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	25.0% 1/4 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
General disorders Weight loss	33.4% 167/500 • Number of events 240 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	11.9% 30/253 • Number of events 34 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	50.0% 2/4 • Number of events 7 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Hepatobiliary disorders Hepatobiliary - Other	1.6% 8/500 • Number of events 9 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	1.6% 4/253 • Number of events 4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	25.0% 1/4 • Number of events 3 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Metabolism and nutrition disorders ALT	5.6% 28/500 • Number of events 53 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	2.8% 7/253 • Number of events 8 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Metabolism and nutrition disorders AST	7.4% 37/500 • Number of events 72 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	4.7% 12/253 • Number of events 13 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Metabolism and nutrition disorders Alkaline phosphatase	7.0% 35/500 • Number of events 49 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	3.2% 8/253 • Number of events 12 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Metabolism and nutrition disorders Bilirubin (Hyperbilirubinemia)	19.4% 97/500 • Number of events 160 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	8.7% 22/253 • Number of events 37 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	25.0% 1/4 • Number of events 3 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Metabolism and nutrition disorders Creatinine	3.0% 15/500 • Number of events 19 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	2.8% 7/253 • Number of events 8 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	25.0% 1/4 • Number of events 2 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Metabolism and nutrition disorders GFR	0.80% 4/500 • Number of events 9 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.40% 1/253 • Number of events 2 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	25.0% 1/4 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Metabolism and nutrition disorders Hyperuricemia	2.4% 12/500 • Number of events 13 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.40% 1/253 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	25.0% 1/4 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Metabolism and nutrition disorders Hypocalcemia	6.8% 34/500 • Number of events 57 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.40% 1/253 • Number of events 1 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)
Metabolism and nutrition disorders Hypokalemia	10.0% 50/500 • Number of events 84 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	2.4% 6/253 • Number of events 7 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)	0.00% 0/4 • AE was collected up to 30 days after end of study treatment (per protocol) over a period of approximately 3.7 years. Disseminated Intravascular Coagulation (DIC), International Normalized Ratio (INR), Cardiac Troponin T (cTnT), Gastroihntestina (GI), Not Otherwise Specified (NOS), Aspartate Aminotransferase (AST), Genitourinary (GU), Alanine Aminotransferase (ALT), Acute Respiratory Distress Syndrome (ARDS), Absolute Neutrophil Count (ANC)