Trial Outcomes & Findings for Dose-Finding Trial of F-627 in Women With Breast Cancer Receiving Myelotoxic Chemotherapy (NCT NCT01648322)

NCT ID: NCT01648322

Last Updated: 2018-10-03

Results Overview

Number of days In which the patient has had an absolute neutrophil count (ANC) Level \< 2.0 x 10\^9/L after first cycle of chemotherapy

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 232 participants
• Primary outcome timeframe: The first of 4, 21 Day Chemotherapy Cycles
• Results posted on: 2018-10-03

Participant Flow

Participant milestones

Measure	80 µg/kg/Dose of F-627 This dose of F-627 given only to subjects that are to have TC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	240 µg/kg/Dose of F-627 This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	320 µg/kg/Dose of F-627 This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	Neulasta® (Pegfilgrastim) Given to subjects receiving TC or TAC chemotherapy. Neulasta® (pegfilgrastim): Single dose injection given once per chemotherapy cycle.
Overall Study STARTED	35	67	65	65
Overall Study COMPLETED	33	62	60	61
Overall Study NOT COMPLETED	2	5	5	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Dose-Finding Trial of F-627 in Women With Breast Cancer Receiving Myelotoxic Chemotherapy

Baseline characteristics by cohort

Measure	80 µg/kg/Dose of F-627 n=35 Participants This dose of F-627 given only to subjects that are to have TC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	240 µg/kg/Dose of F-627 n=67 Participants This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	320 µg/kg/Dose of F-627 n=65 Participants This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	Neulasta® (Pegfilgrastim) n=65 Participants Given to subjects receiving TC or TAC chemotherapy. Neulasta® (pegfilgrastim): Single dose injection given once per chemotherapy cycle.	Total n=232 Participants Total of all reporting groups
Age, Continuous	48.7 years STANDARD_DEVIATION 10.3 • n=5 Participants	47.9 years STANDARD_DEVIATION 10.1 • n=7 Participants	48.9 years STANDARD_DEVIATION 10.3 • n=5 Participants	48.2 years STANDARD_DEVIATION 10.9 • n=4 Participants	48.4 years STANDARD_DEVIATION 10.4 • n=21 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	67 Participants n=7 Participants	65 Participants n=5 Participants	65 Participants n=4 Participants	232 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
weight	73.28 kg STANDARD_DEVIATION 17.12 • n=5 Participants	70.89 kg STANDARD_DEVIATION 14.44 • n=7 Participants	70.22 kg STANDARD_DEVIATION 12.94 • n=5 Participants	71.28 kg STANDARD_DEVIATION 14.09 • n=4 Participants	71.18 kg STANDARD_DEVIATION 14.32 • n=21 Participants
Height	164.88 cm STANDARD_DEVIATION 5.66 • n=5 Participants	163.58 cm STANDARD_DEVIATION 8.15 • n=7 Participants	162.90 cm STANDARD_DEVIATION 5.66 • n=5 Participants	162.80 cm STANDARD_DEVIATION 6.99 • n=4 Participants	163.37 cm STANDARD_DEVIATION 6.83 • n=21 Participants
ECOG status Grade 0	25 Participants n=5 Participants	40 Participants n=7 Participants	42 Participants n=5 Participants	41 Participants n=4 Participants	148 Participants n=21 Participants
ECOG status Grade 1	10 Participants n=5 Participants	27 Participants n=7 Participants	23 Participants n=5 Participants	24 Participants n=4 Participants	84 Participants n=21 Participants
ECOG status Grade 2	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Cancer Stage at screen I	1 participants n=5 Participants	12 participants n=7 Participants	12 participants n=5 Participants	9 participants n=4 Participants	34 participants n=21 Participants
Cancer Stage at screen II	25 participants n=5 Participants	28 participants n=7 Participants	32 participants n=5 Participants	31 participants n=4 Participants	116 participants n=21 Participants
Cancer Stage at screen III	9 participants n=5 Participants	23 participants n=7 Participants	18 participants n=5 Participants	23 participants n=4 Participants	73 participants n=21 Participants
Cancer Stage at screen IV	0 participants n=5 Participants	4 participants n=7 Participants	3 participants n=5 Participants	2 participants n=4 Participants	9 participants n=21 Participants

PRIMARY outcome

Timeframe: The first of 4, 21 Day Chemotherapy Cycles

Population: per protocol population

Number of days In which the patient has had an absolute neutrophil count (ANC) Level < 2.0 x 10^9/L after first cycle of chemotherapy

Outcome measures

Measure	80 µg/kg/Dose of F-627(TC) n=35 Participants This dose of F-627 given only to subjects that are to have TC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	240 µg/kg/Dose of F-627 (TC) n=37 Participants This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	320 µg/kg/Dose of F-627 (TC) n=31 Participants This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	Neulasta® (Pegfilgrastim) (TC) n=35 Participants Neulasta fixed dose of 6mg given to subjects receiving TC or TAC chemotherapy. Neulasta® (pegfilgrastim): Single dose injection given once per chemotherapy cycle.	240 µg/kg/Dose of F-627 (TAC) n=30 Participants This dose of F-627 given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	320 µg/kg/Dose of F-627 (TAC) n=29 Participants This dose of F-627 given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	Neulasta® (Pegfilgrastim) (TAC) n=30 Participants Neulasta fixed dose of 6mg given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.
Duration of Moderate Neurtopenia Post First Chemotherapy Administration	0.6 days Standard Deviation 1.26	0.6 days Standard Deviation 1.01	0.4 days Standard Deviation 0.75	0.3 days Standard Deviation 0.56	2.1 days Standard Deviation 1.58	2.1 days Standard Deviation 1.46	1.8 days Standard Deviation 1.28

SECONDARY outcome

Timeframe: Measured for each of the 4, 21 day chemotherapy cycles.

Population: PP population

Number of days In which the patient has had an ANC < 1.0 × 10^9/L (Grade 3) or ANC < .5 × 10^9/L (Grade 4) post each chemotherapy

Outcome measures

Measure	80 µg/kg/Dose of F-627(TC) n=35 Participants This dose of F-627 given only to subjects that are to have TC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	240 µg/kg/Dose of F-627 (TC) n=37 Participants This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	320 µg/kg/Dose of F-627 (TC) n=31 Participants This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	Neulasta® (Pegfilgrastim) (TC) n=35 Participants Neulasta fixed dose of 6mg given to subjects receiving TC or TAC chemotherapy. Neulasta® (pegfilgrastim): Single dose injection given once per chemotherapy cycle.	240 µg/kg/Dose of F-627 (TAC) n=30 Participants This dose of F-627 given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	320 µg/kg/Dose of F-627 (TAC) n=29 Participants This dose of F-627 given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	Neulasta® (Pegfilgrastim) (TAC) n=30 Participants Neulasta fixed dose of 6mg given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.
Duration in Days of Grade 3 and Grade 4 Neutropenia for All 4 Chemotherapy Cycles.	0.4 Days Standard Deviation 0.95	0.2 Days Standard Deviation 0.55	0.2 Days Standard Deviation 0.54	0.1 Days Standard Deviation 0.18	1.6 Days Standard Deviation 1.51	1.6 Days Standard Deviation 1.17	1.2 Days Standard Deviation 1.23

SECONDARY outcome

Timeframe: Measured for each of the 4, 21 day chemotherapy cycles.

Population: PP population

The incidence rate of febrile neutropenia for each arm of the study will be recorded for 4 chemotherapy cycles. Each cycle is expected to last 21 Days.

Outcome measures

Measure	80 µg/kg/Dose of F-627(TC) n=35 Participants This dose of F-627 given only to subjects that are to have TC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	240 µg/kg/Dose of F-627 (TC) n=67 Participants This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	320 µg/kg/Dose of F-627 (TC) n=65 Participants This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	Neulasta® (Pegfilgrastim) (TC) n=65 Participants Neulasta fixed dose of 6mg given to subjects receiving TC or TAC chemotherapy. Neulasta® (pegfilgrastim): Single dose injection given once per chemotherapy cycle.	240 µg/kg/Dose of F-627 (TAC) This dose of F-627 given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	320 µg/kg/Dose of F-627 (TAC) This dose of F-627 given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	Neulasta® (Pegfilgrastim) (TAC) Neulasta fixed dose of 6mg given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.
The Incidence Rate of Febrile Neutropenia	0 Participants	0 Participants	2 Participants	2 Participants	—	—	—

SECONDARY outcome

Timeframe: Measured for each of the 4, 21 day chemotherapy cycles.

Population: PP population

Number of says in which the patient has had an ANC Level ANC < 1.5 × 109/L) post each chemotherapy

Outcome measures

Measure	80 µg/kg/Dose of F-627(TC) n=30 Participants This dose of F-627 given only to subjects that are to have TC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	240 µg/kg/Dose of F-627 (TC) n=29 Participants This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	320 µg/kg/Dose of F-627 (TC) n=30 Participants This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	Neulasta® (Pegfilgrastim) (TC) Neulasta fixed dose of 6mg given to subjects receiving TC or TAC chemotherapy. Neulasta® (pegfilgrastim): Single dose injection given once per chemotherapy cycle.	240 µg/kg/Dose of F-627 (TAC) This dose of F-627 given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	320 µg/kg/Dose of F-627 (TAC) This dose of F-627 given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	Neulasta® (Pegfilgrastim) (TAC) Neulasta fixed dose of 6mg given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.
The Duration in Days of Total Grade 2-4 Neutropenia	2.1 Days Standard Deviation 1.48	2.0 Days Standard Deviation 1.31	1.7 Days Standard Deviation 1.49	—	—	—	—

SECONDARY outcome

Timeframe: Measured for each of the 4, 21 day chemotherapy cycles.

Population: TAC PP population

The time to ANC recovery post nadir for each patient, for each of their chemotherapy cycles will be recorded; recovery for this protocol is defined as achieving an ANC ≥ 2.0 × 10^9/L after the expected ANC nadir (expected nadir is typically 4-6 days post chemotherapy administration). Each chemotherapy cycle is expected to last 21 days.

Outcome measures

Measure	80 µg/kg/Dose of F-627(TC) n=30 Participants This dose of F-627 given only to subjects that are to have TC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	240 µg/kg/Dose of F-627 (TC) n=29 Participants This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	320 µg/kg/Dose of F-627 (TC) n=30 Participants This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	Neulasta® (Pegfilgrastim) (TC) Neulasta fixed dose of 6mg given to subjects receiving TC or TAC chemotherapy. Neulasta® (pegfilgrastim): Single dose injection given once per chemotherapy cycle.	240 µg/kg/Dose of F-627 (TAC) This dose of F-627 given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	320 µg/kg/Dose of F-627 (TAC) This dose of F-627 given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	Neulasta® (Pegfilgrastim) (TAC) Neulasta fixed dose of 6mg given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.
The Time to ANC Recovery Post Nadir	2.4 Days Standard Deviation 1.56	2.0 Days Standard Deviation 1.27	1.9 Days Standard Deviation 1.20	—	—	—	—

SECONDARY outcome

Timeframe: Measured for each of the 4, 21 day chemotherapy cycles.

Population: PP population

The incidence rate of mild, moderate and sever neutropenia for each arm of the study will be recorded for 4 chemotherapy cycles. Each cycle is expected to last 21 Days.

Outcome measures

Measure	80 µg/kg/Dose of F-627(TC) n=35 Participants This dose of F-627 given only to subjects that are to have TC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	240 µg/kg/Dose of F-627 (TC) n=37 Participants This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	320 µg/kg/Dose of F-627 (TC) n=31 Participants This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	Neulasta® (Pegfilgrastim) (TC) n=35 Participants Neulasta fixed dose of 6mg given to subjects receiving TC or TAC chemotherapy. Neulasta® (pegfilgrastim): Single dose injection given once per chemotherapy cycle.	240 µg/kg/Dose of F-627 (TAC) n=30 Participants This dose of F-627 given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	320 µg/kg/Dose of F-627 (TAC) n=29 Participants This dose of F-627 given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	Neulasta® (Pegfilgrastim) (TAC) n=30 Participants Neulasta fixed dose of 6mg given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.
The Incidence Rates of Grade 2, Grade 3, and Grade 4 Neutropenia for All Chemotherapy Cycles	17 Participants	14 Participants	11 Participants	10 Participants	28 Participants	25 Participants	25 Participants

SECONDARY outcome

Timeframe: Measured for each of the 4, 21 day chemotherapy cycles

Population: PP population

The depth of ANC nadir for each cycle is defined as the minimal ANC value for a subject in each chemotherapy cycle. The depth of the ANC nadir for each arm of the study will be recorded for 4 chemotherapy cycles.

Outcome measures

Measure	80 µg/kg/Dose of F-627(TC) n=35 Participants This dose of F-627 given only to subjects that are to have TC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	240 µg/kg/Dose of F-627 (TC) n=37 Participants This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	320 µg/kg/Dose of F-627 (TC) n=31 Participants This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	Neulasta® (Pegfilgrastim) (TC) n=35 Participants Neulasta fixed dose of 6mg given to subjects receiving TC or TAC chemotherapy. Neulasta® (pegfilgrastim): Single dose injection given once per chemotherapy cycle.	240 µg/kg/Dose of F-627 (TAC) n=30 Participants This dose of F-627 given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	320 µg/kg/Dose of F-627 (TAC) n=29 Participants This dose of F-627 given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	Neulasta® (Pegfilgrastim) (TAC) n=30 Participants Neulasta fixed dose of 6mg given to subjects receiving TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.
The Depth of the ANC Nadir for All Chemotherapy Cycles Cycle 1	2.09 x 10^9/L Standard Deviation 1.5	2.41 x 10^9/L Standard Deviation 1.86	3.00 x 10^9/L Standard Deviation 2.61	3.05 x 10^9/L Standard Deviation 2.31	0.68 x 10^9/L Standard Deviation 1.06	0.86 x 10^9/L Standard Deviation 1.41	0.78 x 10^9/L Standard Deviation 1.28
The Depth of the ANC Nadir for All Chemotherapy Cycles Cycle 2	3.45 x 10^9/L Standard Deviation 2.54	3.74 x 10^9/L Standard Deviation 2.09	4.71 x 10^9/L Standard Deviation 3.09	4.11 x 10^9/L Standard Deviation 1.59	1.87 x 10^9/L Standard Deviation 1.65	1.79 x 10^9/L Standard Deviation 1.56	1.65 x 10^9/L Standard Deviation 1.30
The Depth of the ANC Nadir for All Chemotherapy Cycles Cycle 3	3.47 x 10^9/L Standard Deviation 2.18	3.80 x 10^9/L Standard Deviation 2.43	4.91 x 10^9/L Standard Deviation 2.68	4.78 x 10^9/L Standard Deviation 2.36	1.41 x 10^9/L Standard Deviation 1.22	1.43 x 10^9/L Standard Deviation 1.51	1.91 x 10^9/L Standard Deviation 1.37
The Depth of the ANC Nadir for All Chemotherapy Cycles Cycle 4	2.93 x 10^9/L Standard Deviation 1.74	3.56 x 10^9/L Standard Deviation 2.45	4.75 x 10^9/L Standard Deviation 3.45	3.99 x 10^9/L Standard Deviation 2.46	1.35 x 10^9/L Standard Deviation 1.22	1.94 x 10^9/L Standard Deviation 2.15	1.91 x 10^9/L Standard Deviation 1.46

Adverse Events

80 µg/kg/Dose of F-627

Serious events: 0 serious events

Other events: 32 other events

Deaths: 0 deaths

240 µg/kg/Dose of F-627

Serious events: 1 serious events

Other events: 63 other events

Deaths: 0 deaths

320 µg/kg/Dose of F-627

Serious events: 1 serious events

Other events: 61 other events

Deaths: 0 deaths

Neulasta® (Pegfilgrastim)

Serious events: 4 serious events

Other events: 59 other events

Deaths: 0 deaths

Serious adverse events

Measure	80 µg/kg/Dose of F-627 n=35 participants at risk This dose of F-627 given only to subjects that are to have TC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	240 µg/kg/Dose of F-627 n=67 participants at risk This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	320 µg/kg/Dose of F-627 n=65 participants at risk This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	Neulasta® (Pegfilgrastim) n=65 participants at risk Neulasta fixed dose of 6mg given to subjects receiving TC or TAC chemotherapy. Neulasta® (pegfilgrastim): Single dose injection given once per chemotherapy cycle.
Infections and infestations Pneumonia	0.00% 0/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	1.5% 1/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Hepatobiliary disorders Hepatitis Toxic	0.00% 0/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	1.5% 1/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	1.5% 1/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Gastrointestinal disorders Pancreatitis	0.00% 0/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	1.5% 1/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Hepatobiliary disorders Cholecystitis acute	0.00% 0/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	1.5% 1/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Infections and infestations Gastroenteritis	0.00% 0/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	1.5% 1/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Skin and subcutaneous tissue disorders Hypersensitivity vasculitis	0.00% 0/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	1.5% 1/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	1.5% 1/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	3.1% 2/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death

Other adverse events

Measure	80 µg/kg/Dose of F-627 n=35 participants at risk This dose of F-627 given only to subjects that are to have TC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	240 µg/kg/Dose of F-627 n=67 participants at risk This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	320 µg/kg/Dose of F-627 n=65 participants at risk This dose of F-627 given to subjects receiving TC or TAC chemotherapy. F-627: subcutaneous injection given 1 per chemotherapy.	Neulasta® (Pegfilgrastim) n=65 participants at risk Neulasta fixed dose of 6mg given to subjects receiving TC or TAC chemotherapy. Neulasta® (pegfilgrastim): Single dose injection given once per chemotherapy cycle.
Skin and subcutaneous tissue disorders Alopecia	77.1% 27/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	73.1% 49/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	67.7% 44/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	80.0% 52/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Skin and subcutaneous tissue disorders Erythema	5.7% 2/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	6.0% 4/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	4.6% 3/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	3.1% 2/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
General disorders Asthenia	31.4% 11/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	19.4% 13/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	32.3% 21/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	30.8% 20/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
General disorders Fatigue	14.3% 5/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	19.4% 13/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	18.5% 12/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	15.4% 10/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
General disorders Chest pain	0.00% 0/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	3.0% 2/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	6.2% 4/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Gastrointestinal disorders Nausea	48.6% 17/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	32.8% 22/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	35.4% 23/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	43.1% 28/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Gastrointestinal disorders Diarrhoea	8.6% 3/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	6.0% 4/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	6.2% 4/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	10.8% 7/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Gastrointestinal disorders Vomiting	8.6% 3/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	9.2% 6/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	6.2% 4/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Blood and lymphatic system disorders Neutropenia	17.1% 6/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	37.3% 25/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	32.3% 21/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	26.2% 17/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Blood and lymphatic system disorders Leukopenia	8.6% 3/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	17.9% 12/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	12.3% 8/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	10.8% 7/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Musculoskeletal and connective tissue disorders Bone pain	20.0% 7/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	16.4% 11/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	16.9% 11/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	18.5% 12/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Musculoskeletal and connective tissue disorders Back pain	8.6% 3/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	6.0% 4/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	9.2% 6/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	4.6% 3/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Musculoskeletal and connective tissue disorders Myalgia	5.7% 2/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	4.5% 3/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	1.5% 1/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	6.2% 4/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Musculoskeletal and connective tissue disorders Musculoskeletal pain	8.6% 3/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	6.2% 4/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Musculoskeletal and connective tissue disorders Pain in extremity	5.7% 2/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	1.5% 1/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	4.6% 3/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	1.5% 1/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Nervous system disorders Headache	14.3% 5/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	7.5% 5/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	10.8% 7/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	6.2% 4/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Nervous system disorders Dizziness	8.6% 3/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	1.5% 1/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Respiratory, thoracic and mediastinal disorders Respiratory disorder	5.7% 2/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	1.5% 1/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	3.1% 2/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	3.1% 2/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Metabolism and nutrition disorders Decreased appetite	0.00% 0/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	6.0% 4/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	7.7% 5/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	1.5% 1/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death
Metabolism and nutrition disorders Dehydration	5.7% 2/35 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/67 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	1.5% 1/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death	0.00% 0/65 • Subjects were to be followed up 30 days after the last study visit for identification of AEs. Subsequent to the 30 day AE follow-up, subjects who discontinued due to FN were to be followed up for an additional 30 days to identify further FN events or severe neutropenia (defined as ANC <0.5×109/L) with duration >2 days. Any Grade 3 or 4 AEs or SAEs were to be followed up until they had resolved or stabilized. The NCI CTCAE v4.0 grading system was used in AE reporting to provide a standard language to describe toxicities, to facilitate tabulation and analysis of the data, and to facilitate the assessment of the clinical significance of all AEs. AEs were to be recorded and graded 1 to 5 according to the CTCAE grades provided below: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe and undesirable AE Grade 4 Life-threatening or disabling AE Grade 5 Death

Additional Information

Chief Medical Officer

Generon (shanghai) corporation

Phone: 8621-61760866

Email: tangt@generonbiomed.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60