SPI-2012 vs Pegfilgrastim in Management of Neutropenia in... | NCT02953340

ID	Type	Description	Link
2016-003469-24	EudraCT Number

Label	Type	Description	Intervention Names
(Arm 1): SPI-2012 and TC	Experimental	At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 milligrams (mg)/0.6 milliliter (mL), [3.6 mg granulocyte colony-stimulating factor {G-CSF}] subcutaneously (SC) approximately 24-26 hours after receiving intravenous (IV) infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.	Drug: SPI-2012 Drug: Docetaxel Drug: Cyclophosphamide
(Arm 2): Pegfilgrastim and TC	Experimental	At each cycle for 4 cycles, participants received pegfilgrastim 6 mg (6 mg/0.6 mL GCSF) SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.	Drug: Pegfilgrastim Drug: Docetaxel Drug: Cyclophosphamide

Name	Type	Description	Arm Group Labels	Other Names
SPI-2012	Drug	Supplied in prefilled single-use syringes for subcutaneous injection, administered on Day 2 of each cycle	(Arm 1): SPI-2012 and TC

Measure	Description	Time Frame
Duration of Severe Neutropenia (DSN) in Cycle 1	DSN was defined as the number of days of severe neutropenia (absolute neutrophil count [ANC] <0.5×10^9 per liter [L]) from the first occurrence of ANC below the threshold.	Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days)

Measure	Description	Time Frame
Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1	Time to ANC recovery was defined as the time from chemotherapy administration until the participants ANC increased to >=1.5×10^9/L after the expected nadir. For participants with ANC value >=1.5×10^9/L at all times, time to ANC Recovery was assigned a value of 0.	Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days)

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

New diagnosis of histologically confirmed early-stage breast cancer (ESBC), defined as operable Stage I to Stage IIIA breast cancer
Candidate for adjuvant or neo-adjuvant TC chemotherapy
Eastern Cooperative Oncology Group (ECOG) performance status <= 2
Absolute neutrophil count (ANC) >=1.5×10^9/L
Platelet count >=100×10^9/L
Hemoglobin >9 g/dL
Calculated creatinine clearance > 50 mL/min
Total bilirubin <=1.5 mg/dL
Aspartate aminotransferase (AST) / Serum glutamic oxaloacetic transaminase (SGOT) and Alanine aminotransferase (ALT)/Serum glutamic pyruvic transaminase (SGPT) <=2.5×ULN (upper limit of normal)
Alkaline phosphatase <=2.0×ULN

Key Exclusion Criteria:

Active concurrent malignancy (except non melanoma skin cancer or carcinoma in situ of the cervix) or life-threatening disease
Locally recurrent/metastatic breast cancer
Known sensitivity to E. coli-derived products
Concurrent adjuvant cancer therapy
Previous exposure to filgrastim, pegfilgrastim, or other G-CSF products in clinical development within 12 months prior to the administration of study drug
Active infection, receiving anti-infectives, or any underlying medical condition that would impair ability to receive protocol treatment
Prior bone marrow or stem cell transplant
Used any investigational drugs, biologics, or devices within 30 days prior to study treatment or plans to use any of these during the course of the study• Radiation therapy within 30 days prior to enrollment
Major surgery within 30 days prior to enrollment

Facility	Status	City	State	ZIP	Country	Contacts
ACRC/ Arizona Clinical Research Center Inc.		Tucson	Arizona	85715	United States
Yuma Regional Cancer Center

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	(Arm 1): SPI-2012 and TC	At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 milligrams (mg)/0.6 milliliter (mL), [3.6 mg granulocyte colony-stimulating factor {G-CSF}] subcutaneously (SC) approximately 24-26 hours after receiving intravenous (IV) infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 28, 2017	Aug 30, 2021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Duration of Severe Neutropenia (DSN) in Cycle 1

DSN was defined as the number of days of severe neutropenia (absolute neutrophil count [ANC] <0.5×10^9 per liter [L]) from the first occurrence of ANC below the threshold.

ITT population included all participants who were randomized.

Posted

Mean

Standard Deviation

Days

Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days)

ID	Title	Description
OG000	(Arm 1): SPI-2012 and TC	At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 mg/0.6 mL, [3.6 mg granulocyte colony-stimulating factor {G-CSF}] SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.
OG001	(Arm 2): Pegfilgrastim and TC	At each cycle for 4 cycles, participants received pegfilgrastim 6 mg (6 mg/0.6 mL G-CSF) SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.

Units	Counts
Participants	OG000118 OG001119

Title

Denominators

Categories

Title	Measurements
	OG0000.31± 0.688 OG0010.39± 0.949

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		t-statistics	The p-values are based on the calculated t-statistics from the bootstrapped sample mean and standard deviation.	< 0.0001		Mean difference	-0.074			2-Sided	95	-0.292	0.129					Non-Inferiority	The study used non inferiority margin of 0.62 days for the above comparison. The non-inferiority of SPI-2012 to Pegfilgrastim was declared if the upper bound of 95% confidence interval (CI) of the difference in mean DSN between the treatment arms was <0.62 days.

Secondary

Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1

Time to ANC recovery was defined as the time from chemotherapy administration until the participants ANC increased to >=1.5×10^9/L after the expected nadir. For participants with ANC value >=1.5×10^9/L at all times, time to ANC Recovery was assigned a value of 0.

ITT population included all participants who were randomized.

Posted

Mean

Standard Deviation

Days

Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days)

ID	Title	Description
OG000	(Arm 1): SPI-2012 and TC	At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 mg/0.6 mL, [3.6 mg granulocyte colony-stimulating factor {G-CSF}] SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.
OG001	(Arm 2): Pegfilgrastim and TC	At each cycle for 4 cycles, participants received pegfilgrastim 6 mg (6 mg/0.6 mL G-CSF) SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.

Secondary

Depth of ANC Nadir in Cycle 1

The depth of ANC Nadir was defined as the lowest ANC value after administration of study drug (SPI-2012 or pegfilgrastim) in Cycle 1.

ITT population included all participants who were randomized. Here 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure at the specified timepoint.

Posted

Mean

Standard Deviation

10^9 cells/L

Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days)

ID	Title	Description
OG000	(Arm 1): SPI-2012 and TC	At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 mg/0.6 mL, [3.6 mg granulocyte colony-stimulating factor {G-CSF}] SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.
OG001	(Arm 2): Pegfilgrastim and TC	At each cycle for 4 cycles, participants received pegfilgrastim 6 mg (6 mg/0.6 mL G-CSF) SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.

Secondary

Number of Participants With Febrile Neutropenia (FN) in Cycle 1

FN was defined as an oral temperature >38.3 degree Celsius (°C) (101.0 degrees Fahrenheit [°F]) or two consecutive readings of >38.0°C (100.4°F) for 2 hours and ANC <1.0×10^9/L.

ITT population included all participants who were randomized.

Posted

Count of Participants

Participants

Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days)

ID	Title	Description
OG000	(Arm 1): SPI-2012 and TC	At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 mg/0.6 mL, [3.6 mg granulocyte colony-stimulating factor {G-CSF}] SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.
OG001	(Arm 2): Pegfilgrastim and TC	At each cycle for 4 cycles, participants received pegfilgrastim 6 mg (6 mg/0.6 mL G-CSF) SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.

Secondary

Duration of Severe Neutropenia (DSN) in Cycles 2, 3 and 4

DSN was defined as the number of days of severe neutropenia (ANC <0.5×10^9/L) from the first occurrence of ANC below the threshold.

ITT population included all participants who were randomized.

Posted

Mean

Standard Deviation

Days

Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle = 21 days)

ID	Title	Description
OG000	(Arm 1): SPI-2012 and TC	At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 mg/0.6 mL, [3.6 mg granulocyte colony-stimulating factor {G-CSF}] SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.
OG001	(Arm 2): Pegfilgrastim and TC	At each cycle for 4 cycles, participants received pegfilgrastim 6 mg (6 mg/0.6 mL G-CSF) SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.

Secondary

Number of Participants With Neutropenic Complications in Cycle 1

Neutropenic complications refer to hospitalizations due to neutropenic events and/or the use of anti-infectives due to neutropenia.

ITT population included all participants who were randomized.

Posted

Count of Participants

Participants

Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days)

ID	Title	Description
OG000	(Arm 1): SPI-2012 and TC	At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 mg/0.6 mL, [3.6 mg granulocyte colony-stimulating factor {G-CSF}] SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.
OG001	(Arm 2): Pegfilgrastim and TC	At each cycle for 4 cycles, participants received pegfilgrastim 6 mg (6 mg/0.6 mL G-CSF) SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.

Secondary

Number of Participants With Febrile Neutropenia in Cycles 2, 3 and 4

FN was defined as an oral temperature >38.3°C (101.0°F) or two consecutive readings of >38.0°C (100.4°F) for 2 hours and ANC <1.0×10^9/L.

ITT population included all participants who were randomized.

Posted

Count of Participants

Participants

Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle = 21 days)

ID	Title	Description
OG000	(Arm 1): SPI-2012 and TC	At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 mg/0.6 mL, [3.6 mg granulocyte colony-stimulating factor {G-CSF}] SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.
OG001	(Arm 2): Pegfilgrastim and TC	At each cycle for 4 cycles, participants received pegfilgrastim 6 mg (6 mg/0.6 mL G-CSF) SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.

Secondary

Relative Dose Intensity (RDI) of TC Chemotherapy

RDI was defined as the percentage of the planned dose of TC chemotherapy that each participant actually received during the study, and is expressed as the total dose received, divided by total dose planned multiplied by 100. The planned dose was defined as the dose that would be given if no doses were missed and/or no dose reductions were made for the number of cycles started. The total planned dose was the sum of planned doses over all cycles.

Safety analysis (SAF) population included all participants who received at least one dose of any protocol-specified drug (TC or SPI-2012 or pegfilgrastim).

Posted

Mean

Standard Deviation

Percentage of planned dose

Cycles 1, 2, 3 and 4 (each cycle = 21 days)

ID	Title	Description
OG000	(Arm 1): SPI-2012 and TC	At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 mg/0.6 mL, [3.6 mg granulocyte colony-stimulating factor {G-CSF}] SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.
OG001	(Arm 2): Pegfilgrastim and TC	At each cycle for 4 cycles, participants received pegfilgrastim 6 mg (6 mg/0.6 mL G-CSF) SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.

Secondary

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death

An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product or study procedure, whether or not considered related to the medicinal product. A TEAE is any AE that occurred from the first dose of study treatment through 12 months after the last dose of study treatment or 35 (±5) days after date of participant early discontinuation. SAE is defined as any AE which meets any of the following criteria: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in a persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, includes important medical events.

SAF population included all participants who received at least one dose of any protocol-specified drug (TC or SPI-2012 or pegfilgrastim). Data was summarized and reported for Treatment and Follow-up period separately for both groups.

Posted

Count of Participants

Participants

Up to 4 cycles (each cycle = 21 days) plus a 12-month follow-up from the last dose (up to 15 months)

ID	Title	Description
OG000	(Arm 1): SPI-2012 and TC	At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 mg/0.6 mL, [3.6 mg granulocyte colony-stimulating factor {G-CSF}] SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation.

Secondary

Number of Participants With Clinically Significant Laboratory Abnormalities

The number of participants with clinically significant hematology (including basophils, basophils/leukocytes, eosinophils, eosinophils/leukocytes, hematocrit, hemoglobin, lymphocytes, lymphocytes/leukocytes, monocytes, monocytes/leukocytes, neutrophils, neutrophils/leukocytes, platelets, and white blood cells) and serum chemistry (including alanine aminotransferase [ALT], alkaline phosphatase [ALP], aspartate aminotransferase [AST], bilirubin, calcium, cholesterol, creatinine, potassium, sodium, and triglycerides) laboratory abnormalities were reported. Clinically significant findings in laboratory parameters were based on investigator's discretion according to Common Technical Criteria for Adverse Events (CTCAE) Version 4.03.

SAF population included all participants who received at least one dose of any protocol-specified drug (TC or SPI-2012 or pegfilgrastim).

Posted

Count of Participants

Participants

Up to 4 cycles (each cycle = 21 days) plus a 12-month follow-up from the last dose (up to 15 months)

ID	Title	Description
OG000	(Arm 1): SPI-2012 and TC	At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 mg/0.6 mL, [3.6 mg granulocyte colony-stimulating factor {G-CSF}] SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Deep vein thrombosis	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG0030 affected118 at risk
Hypotension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Administration site reaction	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Chest pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Pyrexia	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Delirium	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0002 affected117 at risk EG0010 affected118 at risk EG0020 affected117 at risk EG003
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Rib fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Seroma	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0010 affected118 at risk EG0020 affected117 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
White blood cell count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Supraventricular tachycardia	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected117 at risk EG0010 affected118 at risk EG0020 affected117 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0010 affected118 at risk EG0021 affected117 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0010 affected118 at risk EG0021 affected117 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0012 affected118 at risk EG0020 affected117 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0013 affected118 at risk EG0020 affected117 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0012 affected118 at risk EG0020 affected117 at risk EG003
Syncope	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0010 affected118 at risk EG0020 affected117 at risk EG003
Dizziness	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0010 affected118 at risk EG0020 affected117 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected117 at risk EG0010 affected118 at risk EG0020 affected117 at risk EG003
Enterocolitis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected117 at risk EG0010 affected118 at risk EG0020 affected117 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected117 at risk EG0010 affected118 at risk EG0020 affected117 at risk EG003
Skin disorder	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected117 at risk EG0010 affected118 at risk EG0020 affected117 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0010 affected118 at risk EG0020 affected117 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Fluid overload	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Bronchitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Bronchitis viral	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Cellulitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Chest wall abscess	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Cystitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Enterocolitis infectious	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected117 at risk EG0010 affected118 at risk EG0020 affected117 at risk EG003
Escherichia bacteraemia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected117 at risk EG0010 affected118 at risk EG0020 affected117 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected117 at risk EG0010 affected118 at risk EG0020 affected117 at risk EG003
Pneumonia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0012 affected118 at risk EG0020 affected117 at risk EG003
Pyelonephritis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected117 at risk EG0010 affected118 at risk EG0020 affected117 at risk EG003
Sepsis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0011 affected118 at risk EG0020 affected117 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Flushing	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0009 affected117 at risk EG00110 affected118 at risk EG0020 affected117 at risk EG0032 affected118 at risk
Hot flush	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG00010 affected117 at risk EG0018 affected118 at risk EG0021 affected117 at risk EG003
Hypertension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected117 at risk EG0018 affected118 at risk EG0021 affected117 at risk EG003
Hypotension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0006 affected117 at risk EG0013 affected118 at risk EG0020 affected117 at risk EG003
Fatigue	General disorders	MedDRA 18.0	Systematic Assessment	EG00040 affected117 at risk EG00151 affected118 at risk EG0020 affected117 at risk EG003
Pyrexia	General disorders	MedDRA 18.0	Systematic Assessment	EG00025 affected117 at risk EG00126 affected118 at risk EG0021 affected117 at risk EG003
Oedema peripheral	General disorders	MedDRA 18.0	Systematic Assessment	EG00012 affected117 at risk EG00115 affected118 at risk EG0022 affected117 at risk EG003
Asthenia	General disorders	MedDRA 18.0	Systematic Assessment	EG00015 affected117 at risk EG00111 affected118 at risk EG0020 affected117 at risk EG003
Pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0005 affected117 at risk EG00111 affected118 at risk EG0020 affected117 at risk EG003
Chills	General disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected117 at risk EG0016 affected118 at risk EG0020 affected117 at risk EG003
Malaise	General disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected117 at risk EG0016 affected118 at risk EG0020 affected117 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG00018 affected117 at risk EG00111 affected118 at risk EG0021 affected117 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0005 affected117 at risk EG0018 affected118 at risk EG0020 affected117 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG00044 affected117 at risk EG00154 affected118 at risk EG0020 affected117 at risk EG003
White blood cell count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG00022 affected117 at risk EG00131 affected118 at risk EG0021 affected117 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG00016 affected117 at risk EG00122 affected118 at risk EG0021 affected117 at risk EG003
Platelet count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG00012 affected117 at risk EG0013 affected118 at risk EG0020 affected117 at risk EG003
White blood cell count increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0009 affected117 at risk EG0013 affected118 at risk EG0020 affected117 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0005 affected117 at risk EG0016 affected118 at risk EG0020 affected117 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG00037 affected117 at risk EG00137 affected118 at risk EG0020 affected117 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG00022 affected117 at risk EG00111 affected118 at risk EG0021 affected117 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG00010 affected117 at risk EG0019 affected118 at risk EG0021 affected117 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0008 affected117 at risk EG00117 affected118 at risk EG0022 affected117 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0008 affected117 at risk EG00114 affected118 at risk EG0021 affected117 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0009 affected117 at risk EG00110 affected118 at risk EG0020 affected117 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected117 at risk EG0017 affected118 at risk EG0020 affected117 at risk EG003
Headache	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG00031 affected117 at risk EG00135 affected118 at risk EG0020 affected117 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0009 affected117 at risk EG00116 affected118 at risk EG0020 affected117 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0009 affected117 at risk EG00114 affected118 at risk EG0021 affected117 at risk EG003
Dizziness	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0006 affected117 at risk EG00112 affected118 at risk EG0021 affected117 at risk EG003
Lacrimation increased	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected117 at risk EG0017 affected118 at risk EG0020 affected117 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00050 affected117 at risk EG00161 affected118 at risk EG0021 affected117 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00038 affected117 at risk EG00140 affected118 at risk EG0021 affected117 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00026 affected117 at risk EG00124 affected118 at risk EG0020 affected117 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00014 affected117 at risk EG00120 affected118 at risk EG0020 affected117 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00014 affected117 at risk EG00119 affected118 at risk EG0021 affected117 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00014 affected117 at risk EG0019 affected118 at risk EG0021 affected117 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0009 affected117 at risk EG00110 affected118 at risk EG0020 affected117 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected117 at risk EG0019 affected118 at risk EG0020 affected117 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG00040 affected117 at risk EG00143 affected118 at risk EG0021 affected117 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG00013 affected117 at risk EG00111 affected118 at risk EG0020 affected117 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG00010 affected117 at risk EG0019 affected118 at risk EG0020 affected117 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected117 at risk EG0016 affected118 at risk EG0020 affected117 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG00047 affected117 at risk EG00151 affected118 at risk EG0021 affected117 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG00026 affected117 at risk EG00123 affected118 at risk EG0020 affected117 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG00018 affected117 at risk EG00115 affected118 at risk EG0022 affected117 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG00017 affected117 at risk EG00112 affected118 at risk EG0024 affected117 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG00014 affected117 at risk EG00111 affected118 at risk EG0021 affected117 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG00023 affected117 at risk EG00119 affected118 at risk EG0020 affected117 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected117 at risk EG0018 affected118 at risk EG0022 affected117 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected117 at risk EG0018 affected118 at risk EG0020 affected117 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0005 affected117 at risk EG0019 affected118 at risk EG0021 affected117 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0003 affected117 at risk EG0016 affected118 at risk EG0021 affected117 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0003 affected117 at risk EG0017 affected118 at risk EG0020 affected117 at risk EG003
Candida infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected117 at risk EG0017 affected118 at risk EG0020 affected117 at risk EG003
Radiation skin injury	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected117 at risk EG0010 affected118 at risk EG0022 affected117 at risk EG003

ID	Term
D000380	Agranulocytosis
D007970	Leukopenia
D000095542	Cytopenia
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D007960	Leukocyte Disorders
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D063088	Phosphoramides
D009943	Organophosphorus Compounds

ID	Title	Description
BG000	(Arm 1): SPI-2012 and TC	At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 mg/0.6 mL, [3.6 mg granulocyte colony-stimulating factor {G-CSF}] SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.
BG001	(Arm 2): Pegfilgrastim and TC	At each cycle for 4 cycles, participants received pegfilgrastim 6 mg (6 mg/0.6 mL G-CSF) SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	(Arm 1): SPI-2012 and TC	At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 mg / 0.6 mL, [3.6 mg G-CSF] SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after the last study treatment or patient discontinuation.	0	117	12	117	115	117
EG001	(Arm 2): Pegfilgrastim and TC	At each cycle for 4 cycles, participants received pegfilgrastim 6 mg (6 mg/0.6 mL G-CSF) SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m^2 and cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after the last study treatment or patient discontinuation.	1	118	19	118	116	118
EG002	(Arm 1): SPI-2012 and TC: Follow-up Period	In addition to the treatment period, long-term safety follow-up continued for 12 months after last study treatment.	0	117	2	117	33	117
EG003	(Arm 2): Pegfilgrastim and TC: Follow-up Period	In addition to the treatment period, long-term safety follow-up continued for 12 months after last study treatment.	0	118	4	118	48	118

ID	Term
C583329	eflapegrastim
C455861	pegfilgrastim
D000077143	Docetaxel
D003520	Cyclophosphamide