Trial Outcomes & Findings for Study of Rituximab and Bendamustine With or Without Brentuximab Vedotin for CD30 Positive Diffuse Large B-cell Lymphoma (NCT NCT02594163)

Last Updated: 2018-10-16

Results Overview

ORR is defined as the percentage of patients who achieve a Complete Response (CR) (including Complete Metabolic Response (CMR)) or Partial Response (PR) (including Partial Metabolic Response (PMR)) as best response to combination therapy on study

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

Approximately 1 year

Results posted on

2018-10-16

Participant Flow

Participant milestones

Participant milestones
Measure	Rituximab, Bendamustine Control Subjects randomized to the control arm will receive IV infusions of rituximab on day 1 or day 2 and bendamustine on both days 1 and 2 of each 21 day cycle. Rituximab Bendamustine	Brentuximab Vedotin Plus Rituximab Plus Bendamustine Subjects randomized to the brentuximab vedotin arm will receive IV infusions of brentuximab vedotin followed by bendamustine on day 1, and rituximab followed by bendamustine on day 2 of each 21 day cycle. Brentuximab Vedotin Rituximab Bendamustine
Treatment Period STARTED	12	13
Treatment Period COMPLETED	5	1
Treatment Period NOT COMPLETED	7	12
Follow-up Period STARTED	12	13
Follow-up Period COMPLETED	1	1
Follow-up Period NOT COMPLETED	11	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Rituximab, Bendamustine Control Subjects randomized to the control arm will receive IV infusions of rituximab on day 1 or day 2 and bendamustine on both days 1 and 2 of each 21 day cycle. Rituximab Bendamustine	Brentuximab Vedotin Plus Rituximab Plus Bendamustine Subjects randomized to the brentuximab vedotin arm will receive IV infusions of brentuximab vedotin followed by bendamustine on day 1, and rituximab followed by bendamustine on day 2 of each 21 day cycle. Brentuximab Vedotin Rituximab Bendamustine
Treatment Period Progressive disease	2	3
Treatment Period Adverse Event	1	5
Treatment Period Physician Decision	1	3
Treatment Period Study termination by sponsor	2	1
Treatment Period Other, Non-AE	1	0
Follow-up Period Withdrawal by Subject	0	1
Follow-up Period Study Termination by Sponsor	6	4
Follow-up Period Lost to Follow-up	1	0
Follow-up Period Death	2	5
Follow-up Period Adverse Event	0	1
Follow-up Period Progressive Disease	2	0
Follow-up Period Physician Decision	0	1

Baseline Characteristics

Study of Rituximab and Bendamustine With or Without Brentuximab Vedotin for CD30 Positive Diffuse Large B-cell Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab, Bendamustine Control n=12 Participants Subjects randomized to the control arm will receive IV infusions of rituximab on day 1 or day 2 and bendamustine on both days 1 and 2 of each 21 day cycle. Rituximab Bendamustine	Brentuximab Vedotin Plus Rituximab Plus Bendamustine n=13 Participants Subjects randomized to the brentuximab vedotin arm will receive IV infusions of brentuximab vedotin followed by bendamustine on day 1, and rituximab followed by bendamustine on day 2 of each 21 day cycle. Brentuximab Vedotin Rituximab Bendamustine	Total n=25 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Age, Continuous	64.5 years n=5 Participants	68.0 years n=7 Participants	68.0 years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	10 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	11 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Czechia	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Poland	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Italy	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment United Kingdom	1 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment France	4 participants n=5 Participants	2 participants n=7 Participants	6 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0: Normal Activity	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1: Symptoms but ambulatory	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2: In bed less than 50% of the time	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Approximately 1 year

Outcome measures

Outcome measures
Measure	Rituximab, Bendamustine Control n=12 Participants Subjects randomized to the control arm will receive IV infusions of rituximab on day 1 or day 2 and bendamustine on both days 1 and 2 of each 21 day cycle. Rituximab Bendamustine	Brentuximab Vedotin Plus Rituximab Plus Bendamustine n=13 Participants Subjects randomized to the brentuximab vedotin arm will receive IV infusions of brentuximab vedotin followed by bendamustine on day 1, and rituximab followed by bendamustine on day 2 of each 21 day cycle. Brentuximab Vedotin Rituximab Bendamustine
Objective Response Rate (ORR)	91.7 percentage of participants Interval 61.5 to 99.8	61.5 percentage of participants Interval 31.6 to 86.1

SECONDARY outcome

Timeframe: Up to 11.8 months

PFS is defined as the time from randomization to disease progression/relapse, receipt of subsequent lymphoma chemotherapy other than the components of the study treatment regimen, or death from any cause, whichever occurs first.

Outcome measures

Outcome measures
Measure	Rituximab, Bendamustine Control n=12 Participants Subjects randomized to the control arm will receive IV infusions of rituximab on day 1 or day 2 and bendamustine on both days 1 and 2 of each 21 day cycle. Rituximab Bendamustine	Brentuximab Vedotin Plus Rituximab Plus Bendamustine n=13 Participants Subjects randomized to the brentuximab vedotin arm will receive IV infusions of brentuximab vedotin followed by bendamustine on day 1, and rituximab followed by bendamustine on day 2 of each 21 day cycle. Brentuximab Vedotin Rituximab Bendamustine
Progression-free Survival (PFS)	4.9 months Interval 1.6 to 11.8	3.7 months Interval 0.8 to 11.5

SECONDARY outcome

Timeframe: Approximately 1 year

CRR is the proportion of patients who achieve CR (including Complete Metabolic Response (CMR)) as best response to combination therapy on study.

Outcome measures

Outcome measures
Measure	Rituximab, Bendamustine Control n=12 Participants Subjects randomized to the control arm will receive IV infusions of rituximab on day 1 or day 2 and bendamustine on both days 1 and 2 of each 21 day cycle. Rituximab Bendamustine	Brentuximab Vedotin Plus Rituximab Plus Bendamustine n=13 Participants Subjects randomized to the brentuximab vedotin arm will receive IV infusions of brentuximab vedotin followed by bendamustine on day 1, and rituximab followed by bendamustine on day 2 of each 21 day cycle. Brentuximab Vedotin Rituximab Bendamustine
Complete Remission (CR) Rate	8 Participants	7 Participants

SECONDARY outcome

Timeframe: Up to 10.5 months

Population: Patients achieving a CR (including CMR) or PR (including PMR)

DOR is defined as the time from first observation of response to disease progression/relapse, receipt of subsequent lymphoma chemotherapy other than the components of the study treatment regimen, or death from any cause, whichever occurs first.

Outcome measures

Outcome measures
Measure	Rituximab, Bendamustine Control n=11 Participants Subjects randomized to the control arm will receive IV infusions of rituximab on day 1 or day 2 and bendamustine on both days 1 and 2 of each 21 day cycle. Rituximab Bendamustine	Brentuximab Vedotin Plus Rituximab Plus Bendamustine n=8 Participants Subjects randomized to the brentuximab vedotin arm will receive IV infusions of brentuximab vedotin followed by bendamustine on day 1, and rituximab followed by bendamustine on day 2 of each 21 day cycle. Brentuximab Vedotin Rituximab Bendamustine
Duration of Response (DOR)	3.7 months Interval 0.0 to 10.5	4.1 months Interval 0.0 to 10.1

SECONDARY outcome

Timeframe: Up to 1.5 years

Population: Intent-to-treat analysis set

OS is defined as the time randomization to death from any cause

Outcome measures

Outcome measures
Measure	Rituximab, Bendamustine Control n=12 Participants Subjects randomized to the control arm will receive IV infusions of rituximab on day 1 or day 2 and bendamustine on both days 1 and 2 of each 21 day cycle. Rituximab Bendamustine	Brentuximab Vedotin Plus Rituximab Plus Bendamustine n=13 Participants Subjects randomized to the brentuximab vedotin arm will receive IV infusions of brentuximab vedotin followed by bendamustine on day 1, and rituximab followed by bendamustine on day 2 of each 21 day cycle. Brentuximab Vedotin Rituximab Bendamustine
Overall Survival (OS)	14.3 months Interval 3.9 to 18.0	6.5 months Interval 1.9 to 11.9

SECONDARY outcome

Timeframe: Approximately 1 year

Population: Safety population

All AEs are included in the summaries, unless treatment-emergent is specified.

Outcome measures

Outcome measures
Measure	Rituximab, Bendamustine Control n=12 Participants Subjects randomized to the control arm will receive IV infusions of rituximab on day 1 or day 2 and bendamustine on both days 1 and 2 of each 21 day cycle. Rituximab Bendamustine	Brentuximab Vedotin Plus Rituximab Plus Bendamustine n=13 Participants Subjects randomized to the brentuximab vedotin arm will receive IV infusions of brentuximab vedotin followed by bendamustine on day 1, and rituximab followed by bendamustine on day 2 of each 21 day cycle. Brentuximab Vedotin Rituximab Bendamustine
Number and Severity of Adverse Events (AEs) Treatment-Emergent Adverse Event	11 Participants	13 Participants
Number and Severity of Adverse Events (AEs) Treatment-Related Adverse Event	10 Participants	13 Participants
Number and Severity of Adverse Events (AEs) Brentuximab Vedotin-Related Adverse Event	0 Participants	11 Participants
Number and Severity of Adverse Events (AEs) Rituximab-Related Adverse Event	6 Participants	10 Participants
Number and Severity of Adverse Events (AEs) Bendamustine-Related Adverse Event	10 Participants	13 Participants
Number and Severity of Adverse Events (AEs) Adverse Event with Outcome of Death	0 Participants	1 Participants
Number and Severity of Adverse Events (AEs) Serious Adverse Event	3 Participants	8 Participants
Number and Severity of Adverse Events (AEs) Treatment-Related Serious Adverse Event	3 Participants	3 Participants
Number and Severity of Adverse Events (AEs) Adverse Event Leading to Dose Delay	3 Participants	0 Participants
Number and Severity of Adverse Events (AEs) Adverse Event Leading to Treatment Discontinuation	1 Participants	5 Participants
Number and Severity of Adverse Events (AEs) Grade 3-5 Treatment-Emergent Adverse Event	4 Participants	11 Participants

Adverse Events

Rituximab, Bendamustine Control

Serious events: 3 serious events

Other events: 11 other events

Deaths: 2 deaths

Brentuximab Vedotin Plus Rituximab Plus Bendamustine

Serious events: 8 serious events

Other events: 13 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Seattle Genetics, Inc.

Phone: 855-473-2436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Rituximab, Bendamustine Control n=12 participants at risk Subjects randomized to the control arm will receive IV infusions of rituximab on day 1 or day 2 and bendamustine on both days 1 and 2 of each 21 day cycle. Rituximab Bendamustine	Brentuximab Vedotin Plus Rituximab Plus Bendamustine n=13 participants at risk Subjects randomized to the brentuximab vedotin arm will receive IV infusions of brentuximab vedotin followed by bendamustine on day 1, and rituximab followed by bendamustine on day 2 of each 21 day cycle. Brentuximab Vedotin Rituximab Bendamustine
Infections and infestations Sepsis	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	15.4% 2/13 • Number of events 2 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Infections and infestations Infection	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Infections and infestations Kidney infection	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Infections and infestations Lymphangitis	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Infections and infestations Pneumonia	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Infections and infestations Pneumonia viral	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Blood and lymphatic system disorders Anaemia	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Blood and lymphatic system disorders Febrile neutropenia	8.3% 1/12 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	0.00% 0/13 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Blood and lymphatic system disorders Histiocytosis haematophagic	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
General disorders Pyrexia	8.3% 1/12 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
General disorders Asthenia	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
General disorders Fatigue	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
General disorders General physical health deterioration	8.3% 1/12 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	0.00% 0/13 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma refractory	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to peritoneum	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Investigations Blood creatinine increased	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 2 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Investigations Neutrophil count decreased	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Investigations Platelet count decreased	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 2 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Investigations White blood cell count decreased	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 3 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Gastrointestinal disorders Abdominal pain	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Nervous system disorders Transient ischaemic attack	8.3% 1/12 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	0.00% 0/13 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/12 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.	7.7% 1/13 • Number of events 1 • 1 year All AEs (regardless of relationship to study drug) should be recorded from study Day 1 (during and postdose) through the end of the safety reporting period. AE severity is graded using the NCI CTCAE, Version 4.03.